- Email: [email protected]
Preliminary results from phase Ib study of spartalizumab plus chemotherapy for advanced non-small cell lung cancer (NSCLC)
abstracts
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Survival prolongation by rationale innovative genomics (SPRING): An international WIN consortium phase I study exploring safety and efficacy of avelumab, palbociclib, and axitinib in advanced non-small cell lung cancer (NSCLC) with integrated genomic and transcriptomic correlates
B. Solomon1, A. Callejo2, J. Bar3, G. Berchem4, L. Bazhenova5, P. Saintigny6, E. Raymond7, N. Girard8, R. Sulaiman9, C. Bresson10, F. Wunder10, J.J. Lee11, J. Raynaud12, E. Rubin13, B. Young14, V. Lazar10, E. Felip15, A. Onn3, B. Leyland-Jones16, R. Kurzrock5 1 Avera Medical Group Oncology & Hematology, Avera Cancer Institute, Sioux Falls, SD, USA, 2Medical Oncology, Vall d’Hebron Institute of Oncology and University Hospital, Barcelona, Spain, 3Oncology, Chaim Sheba Medical Center, Ramat Gan, Israel, 4 Hemato-Oncology, Centre Hospitalier de Luxembourg, Luxembourg, 5Medicine, UC San Diego Moores Cancer Center, University of California, La Jolla, CA, USA, 6 Department of Translational Research and Innovation, Centre Le´on Be´rard, Lyon, France, 7Medical Oncology, Centre Hospitalier Paris Saint-Joseph, Paris, France, 8 Oncology, Institut Curie, Paris, France, 9Physicians Laboratory, Avera Cancer Institute, Sioux Falls, SD, USA, 10Worldwide Innovative Network (WIN), Villejuif, France, 11 Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA, 12ARC Foundation for cancer research, Villejuif, France, 13Shraga Segal Department of Microbiology, Immunology and Genetics, Ben-Gurion University of the Negev, Beer-Sheva, Israel, 14Bowden WIN Laboratory, Bowden WIN Laboratory, Murrieta, CA, USA, 15Medical Oncology Service (Lung Cancer Unit), Vall d’Hebron University Hospital, Barcelona, Spain, 16Medical Oncology, Avera Cancer Institute, Sioux Falls, SD, USA Background: In prior published work, the Worldwide Innovative Network (WIN) Consortium described the Simplified Interventional Mapping System (SIMS) algorithm, based on the hypothesis that both genomic and transcriptomic data are important for matching to a tri-therapy regimen. To account for variation in transcription levels between different tissues, gene by gene tumor RNA levels are normalized against RNA levels in analogous biopsied normal tissue. SPRING is the first trial to assess a SIMS-based tri-therapy regimen in advanced NSCLC. Methods: Patients with metastatic NSCLC (no EGFR or ALK alterations; no ROS1 alteration if tested; PD-L1 unrestricted; 2 prior therapy lines) were treated with avelumab, palbociclib, and axitinib (3 þ 3 dose escalation design). After consent, biopsies of tumor and normal endobronchial mucosa were obtained on all patients for analysis on a central genomics/transcriptomics platform and retrospective SIMS algorithm validation. A safety monitoring committee reviews study conduct at least weekly. Results: Twelve patients have been treated (3 at dose level 1; 6, dose level 2; 3, dose level 3). Three dose-limiting toxicities (DLTs) at least possibly drug related occurred: 1 DLT at dose level 2 (Grade 3 (G3) infusion reaction); 2 DLTs at dose level 3 (G3 hand/foot syndrome and a G5 respiratory failure). The partial response (PR) rate was 44% (4/9 patients who have reached restaging including 2/3 patients at dose level 1; two PRs are in patients who failed prior pembrolizumab). The maximum tolerated dose was avelumab 10 mg/kg IV q2weeks, axitinib 5 mg po bid, palbociclib 75 mg po daily (7 days off; 21 days on) (dose level 2). Conclusions: The tri-therapy combination of avelumab, axitinib, and palbociclib is tolerable with early evidence of activity including in NSCLC patients who failed a prior checkpoint inhibitor. Expansion cohorts are being added to further explore safety of a recommended phase II dose. Transcriptomic and genomic correlates of response are being assessed. Clinical trial identification: NCT03386929; First posted: December 29, 2017. Legal entity responsible for the study: Worldwide Innovative Network (WIN) Association - WIN Consortium. Funding: ARC Foundation for Cancer Research and Pfizer. Disclosure: B. Solomon: Travel / Accommodation / Expenses: Elekta. A. Callejo: Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boerhinger; Speaker Bureau / Expert testimony: Sanofi; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS; Speaker Bureau / Expert testimony: KYOWA KIRIN ; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Celgene. J. Bar: Honoraria (self), Advisory / Consultancy: Roche; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution):
v648 | NSCLC, Metastatic
AstraZeneca; Advisory / Consultancy: Genentech; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: AbbVie; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy: Takeda; Advisory / Consultancy: Vascular Biogenics; Research grant / Funding (institution): MedImmune. G. Berchem: Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Celgene. L. Bazhenova: Advisory / Consultancy: Takeda; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: AbbVie; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Loxo Oncology; Shareholder / Stockholder / Stock options: Epic Sciences; Research grant / Funding (institution): Beyondspring Pharma. P. Saintigny: Honoraria (self), Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Honoraria (self), Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Research grant / Funding (self), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): HTG Diagnostics. E. Raymond: Full / Part-time employment: Genoscience; Full / Part-time employment: Scor; Advisory / Consultancy: Pharmaengine; Travel / Accommodation / Expenses: Merck. N. Girard: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Hoffmann-La Roche; Advisory / Consultancy: Lilly; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Takeda; Advisory / Consultancy: GSK; Advisory / Consultancy: AbbVie. R. Sulaiman: Full / Part-time employment: Physicians Laboratory . E. Rubin: Travel / Accommodation / Expenses: Roche. V. Lazar: Licensing / Royalties: Worldwide Innovative Network Association. E. Felip: Advisory / Consultancy, Speaker Bureau / Expert testimony: ABBVIE; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: Blue Print Medicines; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy: Guardant Health; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck MGaA; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp & Domme; Advisory / Consultancy, Speaker Bureau / Expert testimony: NOVARTIS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy: JANSSEN; Research grant / Funding (institution): Fundation Merck Salud; Research Grant / Funding (Institution): Grant For Oncology Innovation Emd Serono. A. Onn: Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca. B. LeylandJones: Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testimony: Exelixis; Speaker Bureau / Expert testimony: Genentech; Speaker Bureau / Expert testimony: Puma; Travel / Accommodation / Expenses: NFCR; Travel / Accommodation / Expenses: AkesoGen. R. Kurzrock: Shareholder / Stockholder / Stock options, Co-founder: CureMatch; Shareholder / Stockholder / Stock options: IDbyDNA; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Soluventis; Advisory / Consultancy: Gaido; Advisory / Consultancy: Loxo Oncology; Advisory / Consultancy: Xbiotech; Advisory / Consultancy: Acurate Therapeutics; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy: NeoMed; Research grant / Funding (institution): uardant Health; Research grant / Funding (institution): Grifols; Research grant / Funding (institution): Konica Minolta; Research grant / Funding (institution): OmniSeq; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Sequenom; Research grant / Funding (institution): Foundation Medicine. All other authors have declared no conflicts of interest.
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Preliminary results from phase Ib study of spartalizumab plus chemotherapy for advanced non-small cell lung cancer (NSCLC)
A. Santoro1, P. Garrido Lopez2, D.S.W. Tan3, L. Paz-Ares4, F. Shepherd5, A. Bearz6, F. Barlesi7, J.F. Vansteenkiste8, T.M. Kim9, T.R. Overbeck10, I.I. Rybkin11, E. Felip12, W. Zhou13, L. Santarpia14, S. Eddy15, E.S. Schaefer16 1 Dept. of Oncology and Hematology, Istituto Clinico Humanitas, Rozzano, Italy, 2Dept. of Medical Oncology, Hospital Ram on Y Cajal, Madrid, Spain, 3Dept. of Division of Medical Oncology, National Cancer Center Singapore, Singapore, 4Dept. of Medical Oncology, University Hospital 12 de Octubre, Madrid, Spain, 5Dept. of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada, 6 Dept. of Medical Oncology, Centro di Riferimento Oncologico - CRO, Aviano, Italy, 7 Dept. of Multidisciplinary Oncology and Therapeutic Innovations, Aix Marseille University, CNRS, Inserm, Crcm, APHM, Cepcm, CLIP, Marseille, France, 8Dept. of Respiratory Oncology, University Hospital KU Leuven, Leuven, Belgium, 9Dept. of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea, 10Dept. of Medical Oncology and Heamatology, University Medicine Goettingen, Go¨ttingen, Germany, 11Henry Ford Cancer Institute, Henry Ford Health System, Detriot, MI, USA, 12 Dept. of Medical Oncology Service, Vall d’Hebron University Hospital, Barcelona, Spain, 13Dept. of Biostatistics, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, 14Global Drug Development Unit, Novartis Pharma AG, Basel, Switzerland, 15 Clinical Development, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, 16 Dept. of Medical Oncology, Highlands Oncology Group, Fayetteville, AR, USA Background: Spartalizumab (PDR001) is an anti-PD-1 monoclonal antibody that is been explored in different tumor types. Preliminary safety and efficacy results from Groups B (B) and C (C) of a phase Ib study investigating spartalizumab with platinumbased chemotherapy in PD-L1 unselected advanced NSCLC (NCT03064854) are reported here. Methods: Treatment-naive, stage IIIB/IV NSCLC, EGFR/ALK/ROS-1(-) pts, PS 0-1, were assigned to B (non-squamous NSCLC) or C (squamous/non-squamous NSCLC) for 4 cycles (21 day/cycle) of spartalizumab (initial dose – 300 mg Q3W) þ pemetrexed 500 mg/m2 þ cisplatin 75 mg/m2 followed by maintenance spartalizumab þ pemetrexed (in B), or 4 cycles of spartalizumab (initial dose – 300 mg Q3W) þ paclitaxel 200 mg/m2 þ carboplatin AUC 6 followed by maintenance with spartalizumab (in C).
Volume 30 | Supplement 5 | October 2019
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line. Gemcitabine was given as second-line in 9 pts. Epirubicin was always administered with the same schedule at 20 mg/m2 day 1, 8, 15 every 28 until disease progression/ intolerance. Results: Overall response rate was as follows: 4 PR (18 %), 10 SD (45 %) and 8 PD (40%). Median time to progression was 5 months (range 3 – 11). No life threatening event occurred. No grade 3-4 toxicities were observed. Liver toxicity grade 1-2 in 2 pts (10%), thrombocytopenia grade 1 in 2 pts (9%), neutropenia grade 1-2 in 8 pts (40 %), fatigue grade 2 in 7 pts (32%), nausea grade 1 in 4 pts (20%). Conclusions: Epirubicin has a modest clinical activity in pre-treated elderly patients with MPM in progression after one or two regimens, with an acceptable toxicity profile. It could be considered as a palliative treatment. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Annals of Oncology
abstracts
Annals of Oncology
Arqule; Speaker Bureau / Expert Testimony: Takeda, BMS, Roche, AbbVie, Amgen, Celgene, Servier, Gilead, Astrazeneca, Pfizer, Arqule, Lilly, Sandoz, Eisai, Novartis, Bayer, MSD. P. Garrido Lopez: Advisory / Consultancy: Roche, MSD, BMS, Boerhinger Ingelheim, Pfizer, AbbVie, Guardant Health, Novartis, Lilly, AstraZeneca, Janssen, Sysmex, Blueprint Medicines, Takeda; Speaker Bureau / Expert testimony: Roche, MSD, BMS, Pfizer, Novartis, Boerhinger Ingelheim, Rovi; Research grant / Funding (institution), For Clinical Trails: Roche, MSD, BMS, Takeda, Lilly, Pfizer, Novartis, PharmaMar, Celgene, Sanofi, GSK, Theradex Oncology, BluePrint Medicines; Research grant / Funding (institution), For Contracted Research: Guardant Health, Sysmex. D.S.W. Tan: Honoraria (self): Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche, Takeda ; Advisory / Consultancy: Novartis, Bayer, Boehringer Ingelheim, Celgene, AstraZeneca, Eli-lily, Loxo; Research grant / Funding (self): Novartis, AstraZeneca, GlaxoSmithKline, Bayer, Pfizer ; Travel / Accommodation / Expenses: Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche,Takeda . L. Paz-Ares: Honoraria (self): Roche, Novartis, Pfizer, Lilly, BMS, MSD, Merck, Boehringer Ing., AstraZeneca, Amgen, Sanofi, PharmaMar, Takeda; Leadership role: Genomica. F. Shepherd: Honoraria (self): Novartis, AstraZeneca, Roche, BMS, Merck, EMD Serono; Advisory / Consultancy: Novartis, AstraZeneca, Roche, BMS, Merck, EMD Serono; Shareholder / Stockholder / Stock options: AstraZeneca. A. Bearz: Advisory / Consultancy: Takeda; Boehringer Ingelheim, Roche , MSD, Novartis; Speaker Bureau / Expert testimony: Takeda; Boehringer Ingelheim, Roche , MSD; Pfizer; Research grant / Funding (institution): AstraZeneca. F. Barlesi: Honoraria (self): AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer–Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer and Takeda; Research grant / Funding (institution): AbbVie, ACEA, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer–Ingelheim, Eisai, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Genentech, Ipsen, Ignyta, Innate Pharma, Loxo, Novartis, MedImmune, Merck, MSD, Pierre Fabre, Pfizer, Sanofi-Aventis; Non-remunerated activity/ies: Principal Investigator for AstraZeneca, BMS, Merck, Pierre Fabre and F. Hoffmann-La Roche, Ltd, sponsored trials (or ISR). J.F. Vansteenkiste: Honoraria (self), Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD, Roche, Apotex; Research grant / Funding (institution): MSD. T.M. Kim: Research grant / Funding (institution): Alpha Biopharma, AstraZeneca/MedImmune, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, and Yuhan ; Research grant / Funding (self): AstraZeneca ; Non-remunerated activity/ies, Advisory / Consultancy: AstraZeneca, Novartis, Sanofi, and Bayer . T.R. Overbeck: Advisory / Consultancy, Consulting fees: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Medac, MSD, Novartis, Roche/ Genentech; Research grant / Funding (institution), sponsored research agreements: AstraZeneca, Eli Lilly, Roche/Genentech, Sanofi-Aventis; Travel / Accommodation / Expenses, Travel Support: AstraZeneca, Boehringer Ingelheim, Eli Lilly and Roche/Genentech. I.I. Rybkin: Research grant / Funding (institution): Merck, AbbVie, ARMO Biosciences, Beyond Spring Pharmaceutical, BristolMyers Squibb, Novartis, Mirati Therapeutical Inc., Nilogen, Inc., Pfizer, Polaris Group, Syndax Inc., Xcovery Inc., BerGenBio AS, Incyte Corporation, AstraZeneca, Amgen; Advisory / Consultancy: AstraZeneca. E. Felip: Advisory / Consultancy: AbbVie, AstraZeneca, Blue Print Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Guardant Helath, Janssen, Medscape, Merck Kgaa, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda, Touchtime; Speaker Bureau / Expert Testimony: AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Kgaa, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda; Research Grant / Funding (Self): Fundaci on Merck Salud Grant For Oncology Innovation Emd Serono. W. Zhou: Full / Parttime employment: Novartis. L. Santarpia: Full / Part-time employment: Novartis. S. Eddy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. All other authors have declared no conflicts of interest.
Volume 30 | Supplement 5 | October 2019
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Efficacy results of selective AXL inhibitor bemcentinib with pembrolizumab following chemo in patients with NSCLC
nolas5, S. Ponce Aix6, J.M. Trigo Perez1, E. Felip2, P. Brunsvig3, A. Helland4, N. Vi~ E. Carcereny Costa7, M. Domine Gomez8, E. Arriola9, R. Garcia Campelo10, J. Spicer11, J.R. Thompson12, A.L. Ortega Granados13, R.J. Holt14, J.B. Lorens15, M. Shoaib16, A. Siddiqui16, E.V. Schmidt17, M.J. Chisamore18, M.G. Krebs19 1 Medical Oncology, Hospital Universitario Virgen de la Victoria, M alaga, Spain, 2 Medical Oncology Service (Lung Cancer Unit), Vall d’Hebron University Hospital, Barcelona, Spain, 3Department of Oncology, Oslo University Hospital, Oslo, Norway, 4 Radium Hospital/Oncology, University of Oslo, Institute of Clinical Medicine, Oslo, Norway, 5Department of Medical Oncology, Hospital Clinic y Provincial de Barcelona, Barcelona, Spain, 6Medical Oncology, University Hospital 12 De Octubre, Madrid, Spain, 7 Department of Medical Oncology, Catalan Institute of Oncology (ICO Badalona), Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain, 8Medical Oncology, University Hospital "Fundacion Jimenez Diaz", Madrid, Spain, 9Department of Medical Oncology, Hospital del Mar, Barcelona, Spain, 10Medical Oncology Service, CHUAC Complexo Hospitalario Universitario A Coru~ na, A Coru~ na, Spain, 11Oncology, King’s College London, Guy’s Hospital, London, UK, 12Division of Hematology and Oncology, Medical College of Wisconsin Affiliated Hospitals, Menomonee Falls, WI, USA, 13 Oncologıa Me´dica, Complejo Hospitalario de Jaen Universidad de Jaen, Jaen, Spain, 14 Research & Development, BerGenBio ASA, Bergen, Norway, 15Management, BerGenBio ASA, Bergen, Norway, 16Medical Affairs & Monitor, BerGenBio ASA, Bergen, Norway, 17 Clinical Oncology, Merck & Co., Inc., Kenilworth, NJ, USA, 18Oncology Clinical Research, Merck & Co., Inc., Rahway, NJ, USA, 19Manchester Academic Health Sciences Centre, The Christie NHS Foundation Trust and The University of Manchester, Manchester, UK Background: The RTK AXL is implicated in epithelial-to-mesenchymal transition, negative regulation of anti-tumor immunity and resistance to multiple therapies including CPIs. Bemcentinib is a first-in-class, oral, highly selective and potent AXL inhibitor which has been demonstrated to enhance anti-PD1 therapy in the pre-clinical setting. Methods: This PhII trial enrolled 48 advanced lung adenocarcinoma pts with progression on or after 1 prior line of PLT-based chemotherapy. Primary endpoint was ORR according to RECIST 1.1. Additional endpoints included efficacy according to biomarker expression, DCR, PFS, OS and safety. Tumor biopsies were analyzed for AXL by IHC, and PD-L1 expression (22C3 pharmDx). Additional biomarker analysis was also performed. Results: In May 2019, Cohort A was fully recruited: median age 65 (range 39-82) yrs, 61% male, 76% smokers or ex-smokers. Pts had completed a median of 3 treatment cycles. 15 pts were ongoing. Out of 32 pts with available PD-L1, 17 (53%) had TPS <1%, 13 (41%) had TPS 1-49%, and 2 (6%) had TPS >50%. Out of 33 patients with available AXL IHC, 19 (58%) expressed AXL on their tumors. Among pts who had at least 1 evaluable post-baseline scan: ORR was 10/38 (26%) overall, 6/16 (38%) in AXL positive pts (compared to 2/13 (15%) in AXL negative pts), and 7/30 (23%) in pts with TPS 0-49%. 12-mo OS was 54% overall (2 pts lost to follow up). mOS overall was 12.2 mos (95% CI 6.2 – NR). In pts with AXL positive tumors, mOS was 12.2 mos (2.0 – NR) and in AXL negative 12.7 mos (5.6 – NR). In PD-L1 negative pts, mOS was 12.4 mos (5.6-NR). Most common TRAEs (occurring in > 10% of pts) were transaminase increases (35%), asthenia/fatigue (30%), diarrhea (26%), nausea (13%), anemia (11%), and decreased appetite (11%). All cases of transaminase increase were reversible and resolved. 13 pts (28%) had TRAEs grade > 3, all of which were resolved or resolving at the time of writing. No treatment-related deaths were reported. Conclusions: The combination of bemcentinib and pembro was well tolerated and showed promising efficacy in previously treated IO-naı¨ve NSCLC pts, particularly in those with AXL positive disease, including PD-L1 negative pts. mOS of > 12 mos is favorable compared with historical references in the NSCLC second-line setting. Clinical trial identification: NCT03184571. Legal entity responsible for the study: BerGenBio ASA. Funding: BerGenBio ASA. Disclosure: J.M. Trigo Perez: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD. E. Felip: Advisory / Consultancy, Speaker Bureau / Expert testimony: AbbVie; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Blueprint Medicines; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Guardant Health; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Medscape; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck KGaA; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp & Dohme; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Touchtime. A. Helland: Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: PierreFabre; Speaker Bureau / Expert testimony: Pfizer. E. Arriola: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding
doi:10.1093/annonc/mdz260 | v649
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Primary endpoints are recommended dose for expansion (RDE) and ORR by investigator assessment. Results: At data cutoff of 15 May 2019, 38 pts in B and 33 pts in C were treated; 14 pts (36.8%) in B and 4 pts (12.1%) in C are still receiving treatment. Primary reason for discontinuation was progressive disease: 13 of 38 pts (34.2%) in B and 25 of 33 pts (75.8%) in C. DLTs were grade 4 hyponatremia and grade 2 posterior reversible encephalopathy syndrome in B (2 pts) and grade 4 neutropenic colitis in C (1 pt). RDE of spartalizumab in combination with platinum-based chemotherapy for both groups was 300 mg Q3W. Most common AEs (50%, any grade) were nausea (73.7%) and neutropenia (50%) in B; neutropenia (57.6%) and anemia (54.5%) in C. ORR and complete response rate were 50% and 5.3% in B, and 51.5% and 3% in C. Median DOR (months; 95% CI) by investigator assessment was 13.8 (4.9, NE) in B and 8.2 (5.1, 15.4) in C. Median PFS (months; 95% CI) by investigator assessment was 10.4 (5.4, 15.0) in B and 6.3 (4.1, 10.1) in C. Responses were observed at different PD-L1 expression levels with higher rate in PD-L1 tumor proportion score (TPS) 50%. Assessment of additional immune biomarkers is ongoing. Conclusions: RDE of spartalizumab in combination with platinum-based chemotherapy is 300 mg Q3W. Safety profile and preliminary clinical activity are consistent with prior experience with spartalizumab, other immune checkpoint inhibitors and chemotherapy treatments administered. Clinical trial identification: NCT03064854. Editorial acknowledgement: Shiva Krishna Rachamadugu, Novartis Healthcare Pvt Ltd, Hyderabad, India. Legal entity responsible for the study: Novartis Pharmaceuticals Corporation. Funding: Novartis Pharmaceuticals Corporation. Disclosure: A. Santoro: Advisory / Consultancy: BMS, Servier, Gilead, Pfizer, Eisai, Bayer, Msd,
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Survival prolongation by rationale innovative genomics (SPRING): An international WIN consortium phase I study exploring safety and efficacy of avelumab, palbociclib, and axitinib in advanced non-small cell lung cancer (NSCLC) with integrated genomic and transcriptomic correlates
B. Solomon1, A. Callejo2, J. Bar3, G. Berchem4, L. Bazhenova5, P. Saintigny6, E. Raymond7, N. Girard8, R. Sulaiman9, C. Bresson10, F. Wunder10, J.J. Lee11, J. Raynaud12, E. Rubin13, B. Young14, V. Lazar10, E. Felip15, A. Onn3, B. Leyland-Jones16, R. Kurzrock5 1 Avera Medical Group Oncology & Hematology, Avera Cancer Institute, Sioux Falls, SD, USA, 2Medical Oncology, Vall d’Hebron Institute of Oncology and University Hospital, Barcelona, Spain, 3Oncology, Chaim Sheba Medical Center, Ramat Gan, Israel, 4 Hemato-Oncology, Centre Hospitalier de Luxembourg, Luxembourg, 5Medicine, UC San Diego Moores Cancer Center, University of California, La Jolla, CA, USA, 6 Department of Translational Research and Innovation, Centre Le´on Be´rard, Lyon, France, 7Medical Oncology, Centre Hospitalier Paris Saint-Joseph, Paris, France, 8 Oncology, Institut Curie, Paris, France, 9Physicians Laboratory, Avera Cancer Institute, Sioux Falls, SD, USA, 10Worldwide Innovative Network (WIN), Villejuif, France, 11 Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA, 12ARC Foundation for cancer research, Villejuif, France, 13Shraga Segal Department of Microbiology, Immunology and Genetics, Ben-Gurion University of the Negev, Beer-Sheva, Israel, 14Bowden WIN Laboratory, Bowden WIN Laboratory, Murrieta, CA, USA, 15Medical Oncology Service (Lung Cancer Unit), Vall d’Hebron University Hospital, Barcelona, Spain, 16Medical Oncology, Avera Cancer Institute, Sioux Falls, SD, USA Background: In prior published work, the Worldwide Innovative Network (WIN) Consortium described the Simplified Interventional Mapping System (SIMS) algorithm, based on the hypothesis that both genomic and transcriptomic data are important for matching to a tri-therapy regimen. To account for variation in transcription levels between different tissues, gene by gene tumor RNA levels are normalized against RNA levels in analogous biopsied normal tissue. SPRING is the first trial to assess a SIMS-based tri-therapy regimen in advanced NSCLC. Methods: Patients with metastatic NSCLC (no EGFR or ALK alterations; no ROS1 alteration if tested; PD-L1 unrestricted; 2 prior therapy lines) were treated with avelumab, palbociclib, and axitinib (3 þ 3 dose escalation design). After consent, biopsies of tumor and normal endobronchial mucosa were obtained on all patients for analysis on a central genomics/transcriptomics platform and retrospective SIMS algorithm validation. A safety monitoring committee reviews study conduct at least weekly. Results: Twelve patients have been treated (3 at dose level 1; 6, dose level 2; 3, dose level 3). Three dose-limiting toxicities (DLTs) at least possibly drug related occurred: 1 DLT at dose level 2 (Grade 3 (G3) infusion reaction); 2 DLTs at dose level 3 (G3 hand/foot syndrome and a G5 respiratory failure). The partial response (PR) rate was 44% (4/9 patients who have reached restaging including 2/3 patients at dose level 1; two PRs are in patients who failed prior pembrolizumab). The maximum tolerated dose was avelumab 10 mg/kg IV q2weeks, axitinib 5 mg po bid, palbociclib 75 mg po daily (7 days off; 21 days on) (dose level 2). Conclusions: The tri-therapy combination of avelumab, axitinib, and palbociclib is tolerable with early evidence of activity including in NSCLC patients who failed a prior checkpoint inhibitor. Expansion cohorts are being added to further explore safety of a recommended phase II dose. Transcriptomic and genomic correlates of response are being assessed. Clinical trial identification: NCT03386929; First posted: December 29, 2017. Legal entity responsible for the study: Worldwide Innovative Network (WIN) Association - WIN Consortium. Funding: ARC Foundation for Cancer Research and Pfizer. Disclosure: B. Solomon: Travel / Accommodation / Expenses: Elekta. A. Callejo: Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boerhinger; Speaker Bureau / Expert testimony: Sanofi; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS; Speaker Bureau / Expert testimony: KYOWA KIRIN ; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Celgene. J. Bar: Honoraria (self), Advisory / Consultancy: Roche; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution):
v648 | NSCLC, Metastatic
AstraZeneca; Advisory / Consultancy: Genentech; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: AbbVie; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy: Takeda; Advisory / Consultancy: Vascular Biogenics; Research grant / Funding (institution): MedImmune. G. Berchem: Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Celgene. L. Bazhenova: Advisory / Consultancy: Takeda; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: AbbVie; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Loxo Oncology; Shareholder / Stockholder / Stock options: Epic Sciences; Research grant / Funding (institution): Beyondspring Pharma. P. Saintigny: Honoraria (self), Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Honoraria (self), Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Research grant / Funding (self), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): HTG Diagnostics. E. Raymond: Full / Part-time employment: Genoscience; Full / Part-time employment: Scor; Advisory / Consultancy: Pharmaengine; Travel / Accommodation / Expenses: Merck. N. Girard: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Hoffmann-La Roche; Advisory / Consultancy: Lilly; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Takeda; Advisory / Consultancy: GSK; Advisory / Consultancy: AbbVie. R. Sulaiman: Full / Part-time employment: Physicians Laboratory . E. Rubin: Travel / Accommodation / Expenses: Roche. V. Lazar: Licensing / Royalties: Worldwide Innovative Network Association. E. Felip: Advisory / Consultancy, Speaker Bureau / Expert testimony: ABBVIE; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: Blue Print Medicines; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy: Guardant Health; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck MGaA; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp & Domme; Advisory / Consultancy, Speaker Bureau / Expert testimony: NOVARTIS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy: JANSSEN; Research grant / Funding (institution): Fundation Merck Salud; Research Grant / Funding (Institution): Grant For Oncology Innovation Emd Serono. A. Onn: Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca. B. LeylandJones: Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testimony: Exelixis; Speaker Bureau / Expert testimony: Genentech; Speaker Bureau / Expert testimony: Puma; Travel / Accommodation / Expenses: NFCR; Travel / Accommodation / Expenses: AkesoGen. R. Kurzrock: Shareholder / Stockholder / Stock options, Co-founder: CureMatch; Shareholder / Stockholder / Stock options: IDbyDNA; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Soluventis; Advisory / Consultancy: Gaido; Advisory / Consultancy: Loxo Oncology; Advisory / Consultancy: Xbiotech; Advisory / Consultancy: Acurate Therapeutics; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy: NeoMed; Research grant / Funding (institution): uardant Health; Research grant / Funding (institution): Grifols; Research grant / Funding (institution): Konica Minolta; Research grant / Funding (institution): OmniSeq; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Sequenom; Research grant / Funding (institution): Foundation Medicine. All other authors have declared no conflicts of interest.
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Preliminary results from phase Ib study of spartalizumab plus chemotherapy for advanced non-small cell lung cancer (NSCLC)
A. Santoro1, P. Garrido Lopez2, D.S.W. Tan3, L. Paz-Ares4, F. Shepherd5, A. Bearz6, F. Barlesi7, J.F. Vansteenkiste8, T.M. Kim9, T.R. Overbeck10, I.I. Rybkin11, E. Felip12, W. Zhou13, L. Santarpia14, S. Eddy15, E.S. Schaefer16 1 Dept. of Oncology and Hematology, Istituto Clinico Humanitas, Rozzano, Italy, 2Dept. of Medical Oncology, Hospital Ram on Y Cajal, Madrid, Spain, 3Dept. of Division of Medical Oncology, National Cancer Center Singapore, Singapore, 4Dept. of Medical Oncology, University Hospital 12 de Octubre, Madrid, Spain, 5Dept. of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada, 6 Dept. of Medical Oncology, Centro di Riferimento Oncologico - CRO, Aviano, Italy, 7 Dept. of Multidisciplinary Oncology and Therapeutic Innovations, Aix Marseille University, CNRS, Inserm, Crcm, APHM, Cepcm, CLIP, Marseille, France, 8Dept. of Respiratory Oncology, University Hospital KU Leuven, Leuven, Belgium, 9Dept. of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea, 10Dept. of Medical Oncology and Heamatology, University Medicine Goettingen, Go¨ttingen, Germany, 11Henry Ford Cancer Institute, Henry Ford Health System, Detriot, MI, USA, 12 Dept. of Medical Oncology Service, Vall d’Hebron University Hospital, Barcelona, Spain, 13Dept. of Biostatistics, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, 14Global Drug Development Unit, Novartis Pharma AG, Basel, Switzerland, 15 Clinical Development, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, 16 Dept. of Medical Oncology, Highlands Oncology Group, Fayetteville, AR, USA Background: Spartalizumab (PDR001) is an anti-PD-1 monoclonal antibody that is been explored in different tumor types. Preliminary safety and efficacy results from Groups B (B) and C (C) of a phase Ib study investigating spartalizumab with platinumbased chemotherapy in PD-L1 unselected advanced NSCLC (NCT03064854) are reported here. Methods: Treatment-naive, stage IIIB/IV NSCLC, EGFR/ALK/ROS-1(-) pts, PS 0-1, were assigned to B (non-squamous NSCLC) or C (squamous/non-squamous NSCLC) for 4 cycles (21 day/cycle) of spartalizumab (initial dose – 300 mg Q3W) þ pemetrexed 500 mg/m2 þ cisplatin 75 mg/m2 followed by maintenance spartalizumab þ pemetrexed (in B), or 4 cycles of spartalizumab (initial dose – 300 mg Q3W) þ paclitaxel 200 mg/m2 þ carboplatin AUC 6 followed by maintenance with spartalizumab (in C).
Volume 30 | Supplement 5 | October 2019
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line. Gemcitabine was given as second-line in 9 pts. Epirubicin was always administered with the same schedule at 20 mg/m2 day 1, 8, 15 every 28 until disease progression/ intolerance. Results: Overall response rate was as follows: 4 PR (18 %), 10 SD (45 %) and 8 PD (40%). Median time to progression was 5 months (range 3 – 11). No life threatening event occurred. No grade 3-4 toxicities were observed. Liver toxicity grade 1-2 in 2 pts (10%), thrombocytopenia grade 1 in 2 pts (9%), neutropenia grade 1-2 in 8 pts (40 %), fatigue grade 2 in 7 pts (32%), nausea grade 1 in 4 pts (20%). Conclusions: Epirubicin has a modest clinical activity in pre-treated elderly patients with MPM in progression after one or two regimens, with an acceptable toxicity profile. It could be considered as a palliative treatment. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Annals of Oncology
abstracts
Annals of Oncology
Arqule; Speaker Bureau / Expert Testimony: Takeda, BMS, Roche, AbbVie, Amgen, Celgene, Servier, Gilead, Astrazeneca, Pfizer, Arqule, Lilly, Sandoz, Eisai, Novartis, Bayer, MSD. P. Garrido Lopez: Advisory / Consultancy: Roche, MSD, BMS, Boerhinger Ingelheim, Pfizer, AbbVie, Guardant Health, Novartis, Lilly, AstraZeneca, Janssen, Sysmex, Blueprint Medicines, Takeda; Speaker Bureau / Expert testimony: Roche, MSD, BMS, Pfizer, Novartis, Boerhinger Ingelheim, Rovi; Research grant / Funding (institution), For Clinical Trails: Roche, MSD, BMS, Takeda, Lilly, Pfizer, Novartis, PharmaMar, Celgene, Sanofi, GSK, Theradex Oncology, BluePrint Medicines; Research grant / Funding (institution), For Contracted Research: Guardant Health, Sysmex. D.S.W. Tan: Honoraria (self): Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche, Takeda ; Advisory / Consultancy: Novartis, Bayer, Boehringer Ingelheim, Celgene, AstraZeneca, Eli-lily, Loxo; Research grant / Funding (self): Novartis, AstraZeneca, GlaxoSmithKline, Bayer, Pfizer ; Travel / Accommodation / Expenses: Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche,Takeda . L. Paz-Ares: Honoraria (self): Roche, Novartis, Pfizer, Lilly, BMS, MSD, Merck, Boehringer Ing., AstraZeneca, Amgen, Sanofi, PharmaMar, Takeda; Leadership role: Genomica. F. Shepherd: Honoraria (self): Novartis, AstraZeneca, Roche, BMS, Merck, EMD Serono; Advisory / Consultancy: Novartis, AstraZeneca, Roche, BMS, Merck, EMD Serono; Shareholder / Stockholder / Stock options: AstraZeneca. A. Bearz: Advisory / Consultancy: Takeda; Boehringer Ingelheim, Roche , MSD, Novartis; Speaker Bureau / Expert testimony: Takeda; Boehringer Ingelheim, Roche , MSD; Pfizer; Research grant / Funding (institution): AstraZeneca. F. Barlesi: Honoraria (self): AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer–Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer and Takeda; Research grant / Funding (institution): AbbVie, ACEA, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer–Ingelheim, Eisai, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Genentech, Ipsen, Ignyta, Innate Pharma, Loxo, Novartis, MedImmune, Merck, MSD, Pierre Fabre, Pfizer, Sanofi-Aventis; Non-remunerated activity/ies: Principal Investigator for AstraZeneca, BMS, Merck, Pierre Fabre and F. Hoffmann-La Roche, Ltd, sponsored trials (or ISR). J.F. Vansteenkiste: Honoraria (self), Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD, Roche, Apotex; Research grant / Funding (institution): MSD. T.M. Kim: Research grant / Funding (institution): Alpha Biopharma, AstraZeneca/MedImmune, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, and Yuhan ; Research grant / Funding (self): AstraZeneca ; Non-remunerated activity/ies, Advisory / Consultancy: AstraZeneca, Novartis, Sanofi, and Bayer . T.R. Overbeck: Advisory / Consultancy, Consulting fees: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Medac, MSD, Novartis, Roche/ Genentech; Research grant / Funding (institution), sponsored research agreements: AstraZeneca, Eli Lilly, Roche/Genentech, Sanofi-Aventis; Travel / Accommodation / Expenses, Travel Support: AstraZeneca, Boehringer Ingelheim, Eli Lilly and Roche/Genentech. I.I. Rybkin: Research grant / Funding (institution): Merck, AbbVie, ARMO Biosciences, Beyond Spring Pharmaceutical, BristolMyers Squibb, Novartis, Mirati Therapeutical Inc., Nilogen, Inc., Pfizer, Polaris Group, Syndax Inc., Xcovery Inc., BerGenBio AS, Incyte Corporation, AstraZeneca, Amgen; Advisory / Consultancy: AstraZeneca. E. Felip: Advisory / Consultancy: AbbVie, AstraZeneca, Blue Print Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Guardant Helath, Janssen, Medscape, Merck Kgaa, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda, Touchtime; Speaker Bureau / Expert Testimony: AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Kgaa, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda; Research Grant / Funding (Self): Fundaci on Merck Salud Grant For Oncology Innovation Emd Serono. W. Zhou: Full / Parttime employment: Novartis. L. Santarpia: Full / Part-time employment: Novartis. S. Eddy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. All other authors have declared no conflicts of interest.
Volume 30 | Supplement 5 | October 2019
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Efficacy results of selective AXL inhibitor bemcentinib with pembrolizumab following chemo in patients with NSCLC
nolas5, S. Ponce Aix6, J.M. Trigo Perez1, E. Felip2, P. Brunsvig3, A. Helland4, N. Vi~ E. Carcereny Costa7, M. Domine Gomez8, E. Arriola9, R. Garcia Campelo10, J. Spicer11, J.R. Thompson12, A.L. Ortega Granados13, R.J. Holt14, J.B. Lorens15, M. Shoaib16, A. Siddiqui16, E.V. Schmidt17, M.J. Chisamore18, M.G. Krebs19 1 Medical Oncology, Hospital Universitario Virgen de la Victoria, M alaga, Spain, 2 Medical Oncology Service (Lung Cancer Unit), Vall d’Hebron University Hospital, Barcelona, Spain, 3Department of Oncology, Oslo University Hospital, Oslo, Norway, 4 Radium Hospital/Oncology, University of Oslo, Institute of Clinical Medicine, Oslo, Norway, 5Department of Medical Oncology, Hospital Clinic y Provincial de Barcelona, Barcelona, Spain, 6Medical Oncology, University Hospital 12 De Octubre, Madrid, Spain, 7 Department of Medical Oncology, Catalan Institute of Oncology (ICO Badalona), Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain, 8Medical Oncology, University Hospital "Fundacion Jimenez Diaz", Madrid, Spain, 9Department of Medical Oncology, Hospital del Mar, Barcelona, Spain, 10Medical Oncology Service, CHUAC Complexo Hospitalario Universitario A Coru~ na, A Coru~ na, Spain, 11Oncology, King’s College London, Guy’s Hospital, London, UK, 12Division of Hematology and Oncology, Medical College of Wisconsin Affiliated Hospitals, Menomonee Falls, WI, USA, 13 Oncologıa Me´dica, Complejo Hospitalario de Jaen Universidad de Jaen, Jaen, Spain, 14 Research & Development, BerGenBio ASA, Bergen, Norway, 15Management, BerGenBio ASA, Bergen, Norway, 16Medical Affairs & Monitor, BerGenBio ASA, Bergen, Norway, 17 Clinical Oncology, Merck & Co., Inc., Kenilworth, NJ, USA, 18Oncology Clinical Research, Merck & Co., Inc., Rahway, NJ, USA, 19Manchester Academic Health Sciences Centre, The Christie NHS Foundation Trust and The University of Manchester, Manchester, UK Background: The RTK AXL is implicated in epithelial-to-mesenchymal transition, negative regulation of anti-tumor immunity and resistance to multiple therapies including CPIs. Bemcentinib is a first-in-class, oral, highly selective and potent AXL inhibitor which has been demonstrated to enhance anti-PD1 therapy in the pre-clinical setting. Methods: This PhII trial enrolled 48 advanced lung adenocarcinoma pts with progression on or after 1 prior line of PLT-based chemotherapy. Primary endpoint was ORR according to RECIST 1.1. Additional endpoints included efficacy according to biomarker expression, DCR, PFS, OS and safety. Tumor biopsies were analyzed for AXL by IHC, and PD-L1 expression (22C3 pharmDx). Additional biomarker analysis was also performed. Results: In May 2019, Cohort A was fully recruited: median age 65 (range 39-82) yrs, 61% male, 76% smokers or ex-smokers. Pts had completed a median of 3 treatment cycles. 15 pts were ongoing. Out of 32 pts with available PD-L1, 17 (53%) had TPS <1%, 13 (41%) had TPS 1-49%, and 2 (6%) had TPS >50%. Out of 33 patients with available AXL IHC, 19 (58%) expressed AXL on their tumors. Among pts who had at least 1 evaluable post-baseline scan: ORR was 10/38 (26%) overall, 6/16 (38%) in AXL positive pts (compared to 2/13 (15%) in AXL negative pts), and 7/30 (23%) in pts with TPS 0-49%. 12-mo OS was 54% overall (2 pts lost to follow up). mOS overall was 12.2 mos (95% CI 6.2 – NR). In pts with AXL positive tumors, mOS was 12.2 mos (2.0 – NR) and in AXL negative 12.7 mos (5.6 – NR). In PD-L1 negative pts, mOS was 12.4 mos (5.6-NR). Most common TRAEs (occurring in > 10% of pts) were transaminase increases (35%), asthenia/fatigue (30%), diarrhea (26%), nausea (13%), anemia (11%), and decreased appetite (11%). All cases of transaminase increase were reversible and resolved. 13 pts (28%) had TRAEs grade > 3, all of which were resolved or resolving at the time of writing. No treatment-related deaths were reported. Conclusions: The combination of bemcentinib and pembro was well tolerated and showed promising efficacy in previously treated IO-naı¨ve NSCLC pts, particularly in those with AXL positive disease, including PD-L1 negative pts. mOS of > 12 mos is favorable compared with historical references in the NSCLC second-line setting. Clinical trial identification: NCT03184571. Legal entity responsible for the study: BerGenBio ASA. Funding: BerGenBio ASA. Disclosure: J.M. Trigo Perez: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD. E. Felip: Advisory / Consultancy, Speaker Bureau / Expert testimony: AbbVie; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Blueprint Medicines; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Guardant Health; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Medscape; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck KGaA; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp & Dohme; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Touchtime. A. Helland: Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: PierreFabre; Speaker Bureau / Expert testimony: Pfizer. E. Arriola: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding
doi:10.1093/annonc/mdz260 | v649
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Primary endpoints are recommended dose for expansion (RDE) and ORR by investigator assessment. Results: At data cutoff of 15 May 2019, 38 pts in B and 33 pts in C were treated; 14 pts (36.8%) in B and 4 pts (12.1%) in C are still receiving treatment. Primary reason for discontinuation was progressive disease: 13 of 38 pts (34.2%) in B and 25 of 33 pts (75.8%) in C. DLTs were grade 4 hyponatremia and grade 2 posterior reversible encephalopathy syndrome in B (2 pts) and grade 4 neutropenic colitis in C (1 pt). RDE of spartalizumab in combination with platinum-based chemotherapy for both groups was 300 mg Q3W. Most common AEs (50%, any grade) were nausea (73.7%) and neutropenia (50%) in B; neutropenia (57.6%) and anemia (54.5%) in C. ORR and complete response rate were 50% and 5.3% in B, and 51.5% and 3% in C. Median DOR (months; 95% CI) by investigator assessment was 13.8 (4.9, NE) in B and 8.2 (5.1, 15.4) in C. Median PFS (months; 95% CI) by investigator assessment was 10.4 (5.4, 15.0) in B and 6.3 (4.1, 10.1) in C. Responses were observed at different PD-L1 expression levels with higher rate in PD-L1 tumor proportion score (TPS) 50%. Assessment of additional immune biomarkers is ongoing. Conclusions: RDE of spartalizumab in combination with platinum-based chemotherapy is 300 mg Q3W. Safety profile and preliminary clinical activity are consistent with prior experience with spartalizumab, other immune checkpoint inhibitors and chemotherapy treatments administered. Clinical trial identification: NCT03064854. Editorial acknowledgement: Shiva Krishna Rachamadugu, Novartis Healthcare Pvt Ltd, Hyderabad, India. Legal entity responsible for the study: Novartis Pharmaceuticals Corporation. Funding: Novartis Pharmaceuticals Corporation. Disclosure: A. Santoro: Advisory / Consultancy: BMS, Servier, Gilead, Pfizer, Eisai, Bayer, Msd,