- Email: [email protected]
ADP-A2M4 (MAGE-A4) in patients with synovial sarcoma
abstracts 1669O
IMMUNOSARC: A collaborative Spanish (GEIS) and Italian (ISG) sarcoma groups phase I/II trial of sunitinib plus nivolumab in advanced soft tissue and bone sarcomas: Results of the phase IIsoft-tissue sarcoma cohort
Background: The combination of sunitinib (SU) and nivolumab (NI) showed to be safe in the previous phase I of IMMUNOSARC study. We present the results of the phase II of the combination of SU-NI in the advanced STS (pts) cohort. Methods: Pretreated progressing pts, ECOG 0-1, with UPS, synovial (SS), clear cell (CCS), angio(AS)/epithelioid hemangioendothelioma (EH), solitary fibrous tumor (SFT), epithelioid sarcoma (ES), extraskeletal myxoid chondrosarcoma (ECM) or alveolar soft part sarcoma (ASPS) were eligible. SU 37.5 mg/d as induction was given days 1-14 and then reduced to 25mg/d continuously. NI was administered at 3 mg/Kg every 2 weeks from week 3. SU-NI was maintained up to progression or intolerance. Primary end-point was progression-free survival rate (PFSR) at 6 months (m) by RECIST. Secondary end-points: overall survival (OS), objective response rate (ORR) by RECIST and CHOI and toxicity. Results: From Nov 2017 to Dec 2018, 50 eligible pts were included in 8 centres: (M/F 30/20), median age 45y (19-77). Diagnosis was: SS in 9 (18%), CCS in 7 (14%), SFT in 7 (14%), UPS in 6 (12%), ES in 6 (12%), AS in 5 (10%), ECM in 4 (8%), ASPS in 3 (6%) and other in 3 (6%). With a median FU of 6.1 m (0-13), 23 pts (46%) progressed based on RECIST with a median PFS of 5.9 m (95% IC 2.7-9.1) and 9 pts (18%) died, with median OS not reached yet. PFSR at 3 and 6 m based on local evaluation were 69% and 50% respectively and OS at 3 and 6 m were 86% and 77%. Based on central radiological review (RECIST, 43 evaluable pts), there were 1 CR (2.3%), 3 PR (7%), 26 SD (60%, 12 pts showing shrinkage) and 13 PD (30%). By CHOI (31 evaluable), there were 19 PR (61.3%), 8 SD (25.8%) and 4 PD (13%). Most relevant G3/4 toxicities were: AST increase 6 (11.8%), ALT increase 5 (9.8%), neutropenia 5 (9.8%), fatigue 3 (5,9%), thrombocytopenia 2 (3.9%), diarrhea 2 (3.9%), renal function impairment 2 (3.9%), without toxic deaths. Conclusions: The trial met its primary endpoint. SU-NI is an active combination for the treatment of advanced selected STS patients, with 50% of patients free of progression at 6m. Further exploration of immunomodulatory strategies is warranted in selected sarcoma subtypes. Clinical trial identification: NCT03277924. Legal entity responsible for the study: Grupo Espa~ nol de Investigaci on en Sarcomas (GEIS). Funding: Pfizer and BMS. Disclosure: J. Martin Broto: Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Honoraria (self): Bayer; Honoraria (self): Amgen; Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Eisai; Research grant / Funding (self): GlaxoSmithKline . N. Hindi: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Novartis. G.E. Grignani: Travel / Accommodation / Expenses: PharmaMar; Travel / Accommodation / Expenses: Lilly; Travel / Accommodation / Expenses: Novartis. A. Redondo: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy: Clovis; Research grant / Funding (institution): Eisai. C. Valverde: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Research grant / Funding (institution): Bluprint; Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (institution): Karyopharm; Research grant / Funding (institution): Decyphera; Research grant / Funding (institution): Incyte. A. Lopez Pousa: Travel / Accommodation / Expenses: PharmaMar. S. Stacchiotti: Research grant / Funding (institution): Pfizer . E. Palmerini: Advisory / Consultancy, Research grant / Funding (institution): Daiichi Sankyo; Advisory / Consultancy: Amgen; Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Research grant / Funding (institution): Bristol-Myers Squibb (BMS); Research grant / Funding (institution): Pfizer; Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Travel / Accommodation / Expenses: Takeda. D.S. Moura: Research grant / Funding (institution),
v684 | Sarcoma
Travel / Accommodation / Expenses: PharmaMar; Research grant / Funding (institution), Travel / Accommodation / Expenses: Eisai; Research grant / Funding (institution): Novartis. L. D’Ambrosio: Travel / Accommodation / Expenses: PharmaMar; Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy: PSI. J.A. Lopez Martin: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Celgene; Advisory / Consultancy: Novartis; Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties: PharmaMar; Advisory / Consultancy: Chobani; Advisory / Consultancy: Pfizer. All other authors have declared no conflicts of interest.
1670O
ADP-A2M4 (MAGE-A4) in patients with synovial sarcoma
B.A. Van Tine1, M.O. Butler2, D. Araujo3, M.L. Johnson4, J. Clarke5, D. Liebner6, K. Odunsi7, A.J. Olszanski8, S. Basu9, F. Brophy10, T. Holdich11, T. Trivedi10, R.G. Amado10, D.S. Hong12 1 Department of Medical Oncology and Hematology, Washington University School of Medicine, St. Louis, MO, USA, 2Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, ON, Canada, 3Sarcoma Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA, 4Medical Oncology, Sarah Cannon Research Institute-Cancer Centre, Nashville, TN, USA, 5Department of Medicine, Division of Medical Oncology, Duke University School of Medicine, Durham, NC, USA, 6Internal Medicine, Ohio State University, Columbus, OH, USA, 7Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, USA, 8Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA, 9Translational Sciences, Adaptimmune, Philadelphia, PA, USA, 10 Clinical Development, Adaptimmune, Philadelphia, PA, USA, 11Clinical Development, Adaptimmune Ltd, Abingdon, UK, 12Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA Background: This study (NCT03132922) evaluates safety, tolerability, and antitumor activity of ADP-A2M4, genetically engineered autologous specific peptide enhanced affinity receptor (SPEAR) T-cells directed towards a MAGE-A4 peptide expressed in the context of HLA-A*02. Here, we report on a subset of patients (pts) with synovial sarcoma (SS). Methods: In this first-in-human T-cell dose-escalation study, pts who are HLA-A*02þ (excluding *02:05, *02:07), have inoperable or metastatic MAGE-A4þ disease, and meet entry criteria are eligible for treatment. Following apheresis, T-cells are isolated, transduced with MAGE-A4c1032TCR, and expanded. The lymphodepletion chemotherapy increased in intensity as the study progressed, with max dose of 30 mg/m2/d fludarabine x 4 d and 1800 mg/m2/d cyclophosphamide x 2 d. During dose escalation, 3 pts with various tumor types received 0.1x109 (620%), 1x109 (range: 0.5 – 1.2 109), or 5x109 (range: 1.2 – 6 109) transduced cells and were monitored for dose-limiting toxicities (DLTs). During expansion, 30 pts (not only SS) will be treated with 1.2 – 10 x 109 transduced cells. Disease is assessed per RECIST by CT/MRI at wk 6, 12, 18, and 24, and every 3 mo for 2 yr, then every 6 mo or until progression. Correlative studies will investigate transduced cell persistence, phenotype, and function, and serum and tumor microenvironment factors. Results: No DLTs were reported. ADP-A2M4 was well tolerated, with adverse events consistent with chemotherapy or other immunotherapies. 10 pts with SS have been treated in cohort 3 and the expansion phase (30Apr19). Median T-cell dose was 9.7 x 109 (4.49 - 9.98 x 109). 8 pts have post-baseline tumor assessments. There are 3 confirmed partial responses (PR) (-86%, -44%, -54), and 1 unconfirmed PR (-31%) at wk 6. Best response was stable disease in 3 pts (-27% and -15%, ongoing, and þ12%, progressed) and progressive disease in 1. 2 pts have yet to be assessed. Ex vivo analysis of transduced cells from peripheral blood and tumor showed cells were cytolytic and activated in an antigen-specific manner. Conclusions: ADP-A2M4 induced clinical responses in pts with SS. Transduced T-cells expand upon exposure to antigen and are functional. Updated data from this ongoing study will be presented. Clinical trial identification: NCT03132922, First posted on April 28, 2017. Editorial acknowledgement: Debra Brocksmith, MB ChB, PhD, of Envision Pharma Group; contracted by Adaptimmune. Legal entity responsible for the study: Adaptimmune. Funding: Adaptimmune. Disclosure: B.A. Van Tine: Research grant / Funding (self): Pfizer; Research grant / Funding (self): Tracon; Research grant / Funding (self): Merck; Advisory / Consultancy: Epizyme; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy: CytRX; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen; Advisory / Consultancy: Immune Design; Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: Plexxicon; Advisory / Consultancy: Adaptimmune; Speaker Bureau / Expert testimony: Caris. M.O. Butler: Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Merck; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self): Roche; Advisory / Consultancy: Adaptimmune; Advisory / Consultancy: EMD Serono; Advisory / Consultancy: GSK; Advisory / Consultancy: Immunocore; Advisory / Consultancy: Immunovaccine; Research grant / Funding (institution): Takara Bio. M.L. Johnson: Research grant / Funding (institution): BerGenBio; Research grant / Funding (institution): Lilly; Research grant / Funding (institution), Travel / Accommodation / Expenses: EMD Serono; Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): Mirati Therapeutics; Research grant / Funding (institution): Genmab; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research
Volume 30 | Supplement 5 | October 2019
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J. Martin Broto1, N. Hindi1, G.E. Grignani2, J. Martinez Trufero3, A. Redondo4, C. Valverde5, A. Lopez Pousa6, S. Stacchiotti7, E. Palmerini8, E. de Alava9, D.S. Moura10, H. Perez Vega11, P. Collini12, I. Otero13, P. Ledesma14, E. Marchesi15, L. D’Ambrosio2, J.A. Lopez Martin13 1 Instituto de Biomedicina de Sevilla, Seville, Spain, Hospital Universitario Virgen del Rocio, Seville, Spain, 2Medical Oncology, Istituto di Candiolo - FPO - IRCCS, Candiolo, Italy, 3Dept. Medical Oncology, Hospital Miguel Servet, Zaragoza, Spain, 4Dept. Oncologia Medica, Hospital Universitario La Paz, Madrid, Spain, 5Medical Oncology Dept., Vall d’Hebron University Hospital, Barcelona, Spain, 6Medical Oncology Dept., Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, 7Adult Mesenchymal Tumor Medical Oncology Unit, Dept. Cancer Medicine, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, Milan, Italy, 8Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy, 9Dept. Pathology, Hospital Universitario Virgen del Rocio, Seville, Spain, 10 Advanced Therapies and Biomarkers in Oncology Group, Instituto de Biomedicina de Sevilla, Seville, Spain, 11Radiology, Hospital Universitario Virgen del Rocio, Seville, Spain, 12 Department of Diagnostic Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, 13Medical Oncology, Hospital Universitario Doce de Octubrerio Doce de Octubre, Madrid, Spain, 14Clinical Research, Sofpromed, Palma de Mallorca, Spain, 15Clinical Research, Italian Sarcoma Group, Bologna, Italy
Annals of Oncology
abstracts
Annals of Oncology 1671O
Assessment of cardiotoxicity (CT) associated with doxorubicin (dox) in patients (pts) with advanced soft tissue sarcoma (STS) in a phase III randomized trial
R.L. Jones1, A. Wagner2, A. Kawai3, A. Shahir4, V. Soldatenkova5, J. Wright6, W.D. Tap7 Medical Oncology, Royal Marsden Hospital NHS Foundation Trust, London, UK, 2 Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA, 3Musculoskeletal Oncology Dept., National Cancer Center Hospital, Tokyo, Japan, 4Medical Oncology, Eli Lilly and Company, Erl Wood, UK, 5Medical Oncology, Eli Lilly and Company, Indianapolis, IN, USA, 6Medical Oncology, Eli Lilly and Company, Indianapolis, IN, USA, 7 Sarcoma Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA 1
Background: The ANNOUNCE trial evaluated the efficacy of the anti-PDGFR alpha antibody olaratumab þ dox versus placebo þ dox in adults with STS. CT was a secondary safety objective. Methods: Treatment included dox 75mg/m2 on Day 1 of a 21-day cycle for up to 8 cycles, with olaratumab/placebo on Days 1, 8 until progression. Use of the cardioprotectant dexrazoxane was allowed with any cycle and recommended with Cycle 5 and beyond. Pts were monitored for left ventricular ejection fraction (LVEF) decreases after 4, 6, 8 cycles and electrocardiogram (ECG) changes in cycles 1 to 9; both were then monitored every 3 months for 1 year, every 6 months for 1 year, then annually. Eligible pts had a LVEF of 50% at baseline, and were without QTc prolongation, active symptoms of cardiac arrhythmia/dysfunction, and prior anthracycline exposure or mediastinal/pericardial radiation. Results: Median age was 57 years. Medical history included cardiac disorders (n ¼ 33; 6.5%) and ECG abnormalities (n ¼ 1; 0.2%). Of the 506 treated pts from both arms, 504 (99.6%) had at least 1 dox dose, of which, 64.0% received at least 1 dose of dexrazoxane, with 61.0% of these pts starting before Cycle 6. Median dox exposure was 6 cycles/450mg/m2; median duration of CT evaluation was 28 weeks. One pt died due to acute cardiac failure after a cumulative dox dose of 441mg/m2. Adverse events (AEs) of cardiac dysfunction/decreased LVEF are summarized (Table). ECG abnormalities considered AEs occurred in 15 (3.0%) pts. Conclusions: The ANNOUNCE trial prospectively evaluated CT in a large cohort of dox-treated adults with STS, most of whom received dexrazoxane for cardioprotection. Although LVEF decreases were common with routine monitoring, symptomatic cardiac dysfunction was reported infrequently. Frequency of CT was similar in both arms. Longer safety follow-up may be warranted to determine the true rate of CT with higher cumulative doses of dox. Clinical trial identification: NCT02451943. Editorial acknowledgement: Karen Paulsrud, RPh, with Eli Lilly and Company, provided medical writing support. Legal entity responsible for the study: Eli Lilly and Company. Funding: Eli Lilly and Company. Disclosure: R.L. Jones: Advisory / Consultancy: Adaptimmune; Advisory / Consultancy: Blueprint; Advisory / Consultancy: Clinigen; Advisory / Consultancy: Eisai; Advisory / Consultancy: Epizyme; Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: Deciphera; Advisory / Consultancy: Immune Design; Advisory / Consultancy: Eli Lilly and Company; Advisory / Consultancy: Merck; Advisory / Consultancy: PharmaMar; Advisory / Consultancy: Tracon. A.J. Wagner: Advisory /
Volume 30 | Supplement 5 | October 2019
doi:10.1093/annonc/mdz283 | v685
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grant / Funding (institution), Travel / Accommodation / Expenses, Additional travel from: Astellas, AstraZeneca, Boehringer Ingelheim, Clovis, Daiichi Sankyo, Bristol-Myers Squibb, Exelixis, Incyte, Merck, Sysmex Inostics, Vapotherm: Genentech; Research grant / Funding (institution): Stemcentrix; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Checkpoint Therapeutics; Research grant / Funding (institution): Array Biopharma; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): Apexigen; Research grant / Funding (institution), Travel / Accommodation / Expenses: AbbVie; Research grant / Funding (institution): Tarveda; Research grant / Funding (institution): Adaptimmune; Research grant / Funding (institution), Additional advisory for: Gelgene, Boehringer Ingelheim, Sanofi, LOXO, Calithera, Merck, Araxes Pharma, Mersana Therapeutics, BeiGene, Incyte, Guardant Health, Bristol-Myers Squibb, Ribon Therapeutics: Syndax; Research grant / Funding (institution), Additional grant funding from: Boehringer Ingelheim, Sanofi, Hengrui Therapuetics INC, Merck, Daiichi-Sankyo, Lycera, G1 Therapeutics, Dynavax, LOXO, Cytomx, BeiGene, Birdie, Corvus, Incyte, Genocea, Gritstone, Amgen, Bristol-Myers Squibb, Kadmon, Clovis, Acerta, OncoMed, Guardant Health, Takeda, Shattuck Labs, GSK: Neovia. J. Clarke: Research grant / Funding (self): MedPacto; Research grant / Funding (self): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (self): Eli Lilly; Research grant / Funding (self): Genentech; Research grant / Funding (self): Spectrum; Research grant / Funding (self): Adaptimmune; Research grant / Funding (self): Bayer; Research grant / Funding (self): AbbVie; Research grant / Funding (self): Moderna; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Guardant; Advisory / Consultancy: AstraZeneca. D. Liebner: Advisory / Consultancy: Foundation Medicine; Advisory / Consultancy: Blueprint Medicines. K. Odunsi: Research grant / Funding (self): ITeos Therapeutics. A.J. Olszanski: Advisory / Consultancy, Research grant / Funding (self): BristolMyers Squibb; Advisory / Consultancy: Merck; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Array; Advisory / Consultancy, Research grant / Funding (self): EMD Serono; Advisory / Consultancy: Iovance; Advisory / Consultancy: Novartis; Advisory / Consultancy, Research grant / Funding (self): Alkermes; Research grant / Funding (self): Adaptimmune; Research grant / Funding (self): Astellas; Research grant / Funding (self): Boston Biomedical; Research grant / Funding (self): Checkmate Pharmaceutics; Research grant / Funding (self): GSK; Research grant / Funding (self): Immunocore; Research grant / Funding (self): Intensity Therapeutics; Research grant / Funding (self): Kartos; Research grant / Funding (self): Kura; Research grant / Funding (self): Oncoceutics; Research grant / Funding (self): Targovax. S. Basu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Adaptimmune. F. Brophy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Adaptimmune. T. Holdich: Shareholder / Stockholder / Stock options, Full / Part-time employment: Adaptimmune. T. Trivedi: Shareholder / Stockholder / Stock options, Full / Part-time employment: Adaptimmune. R.G. Amado: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Adaptimmune. D.S. Hong: Research grant / Funding (self): AbbVie; Advisory / Consultancy, Research grant / Funding (self): Adaptimmune; Research grant / Funding (self): Amgen; Research grant / Funding (self): AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): Bayer; Research grant / Funding (self): Bristol-Myers Squibb; Research grant / Funding (self): Daiichi-Sankyo; Research grant / Funding (self): Eisai; Research grant / Funding (self): Fate Therapeutics; Advisory / Consultancy, Research grant / Funding (self): Genentech; Research grant / Funding (self), Travel / Accommodation / Expenses: Genmab; Research grant / Funding (self): Ignyta; Advisory / Consultancy, Research grant / Funding (self): Infinity; Research grant / Funding (self): Kite; Research grant / Funding (self): Kyowa; Research grant / Funding (self): Lilly; Research grant / Funding (self), Travel / Accommodation / Expenses: LOXO; Research grant / Funding (self): MedImmune; Research grant / Funding (self): Merck; Research grant / Funding (self), Additional grant funding from: miRNA, Molecular Templates, Mologen, NCI-CTEP, Novartics, Pfizer, Seattle Genetics, Takeda. Additional advisory consulting for: Alpha Insights, Axiom, Baxter, GLG, Group H, Guidepoint Global, Merrimack, Medscape, Numab, Pfizer, Seattle Genetics, Takeda, Trieza Therapeutics, WebMD; Travel support from MiRNA, AACR, ASCO, SITC; ownership interests in Molecular Match, OncoResponse, Presagia Inc: Mirati. All other authors have declared no conflicts of interest.
IMMUNOSARC: A collaborative Spanish (GEIS) and Italian (ISG) sarcoma groups phase I/II trial of sunitinib plus nivolumab in advanced soft tissue and bone sarcomas: Results of the phase IIsoft-tissue sarcoma cohort
Background: The combination of sunitinib (SU) and nivolumab (NI) showed to be safe in the previous phase I of IMMUNOSARC study. We present the results of the phase II of the combination of SU-NI in the advanced STS (pts) cohort. Methods: Pretreated progressing pts, ECOG 0-1, with UPS, synovial (SS), clear cell (CCS), angio(AS)/epithelioid hemangioendothelioma (EH), solitary fibrous tumor (SFT), epithelioid sarcoma (ES), extraskeletal myxoid chondrosarcoma (ECM) or alveolar soft part sarcoma (ASPS) were eligible. SU 37.5 mg/d as induction was given days 1-14 and then reduced to 25mg/d continuously. NI was administered at 3 mg/Kg every 2 weeks from week 3. SU-NI was maintained up to progression or intolerance. Primary end-point was progression-free survival rate (PFSR) at 6 months (m) by RECIST. Secondary end-points: overall survival (OS), objective response rate (ORR) by RECIST and CHOI and toxicity. Results: From Nov 2017 to Dec 2018, 50 eligible pts were included in 8 centres: (M/F 30/20), median age 45y (19-77). Diagnosis was: SS in 9 (18%), CCS in 7 (14%), SFT in 7 (14%), UPS in 6 (12%), ES in 6 (12%), AS in 5 (10%), ECM in 4 (8%), ASPS in 3 (6%) and other in 3 (6%). With a median FU of 6.1 m (0-13), 23 pts (46%) progressed based on RECIST with a median PFS of 5.9 m (95% IC 2.7-9.1) and 9 pts (18%) died, with median OS not reached yet. PFSR at 3 and 6 m based on local evaluation were 69% and 50% respectively and OS at 3 and 6 m were 86% and 77%. Based on central radiological review (RECIST, 43 evaluable pts), there were 1 CR (2.3%), 3 PR (7%), 26 SD (60%, 12 pts showing shrinkage) and 13 PD (30%). By CHOI (31 evaluable), there were 19 PR (61.3%), 8 SD (25.8%) and 4 PD (13%). Most relevant G3/4 toxicities were: AST increase 6 (11.8%), ALT increase 5 (9.8%), neutropenia 5 (9.8%), fatigue 3 (5,9%), thrombocytopenia 2 (3.9%), diarrhea 2 (3.9%), renal function impairment 2 (3.9%), without toxic deaths. Conclusions: The trial met its primary endpoint. SU-NI is an active combination for the treatment of advanced selected STS patients, with 50% of patients free of progression at 6m. Further exploration of immunomodulatory strategies is warranted in selected sarcoma subtypes. Clinical trial identification: NCT03277924. Legal entity responsible for the study: Grupo Espa~ nol de Investigaci on en Sarcomas (GEIS). Funding: Pfizer and BMS. Disclosure: J. Martin Broto: Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Honoraria (self): Bayer; Honoraria (self): Amgen; Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Eisai; Research grant / Funding (self): GlaxoSmithKline . N. Hindi: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Novartis. G.E. Grignani: Travel / Accommodation / Expenses: PharmaMar; Travel / Accommodation / Expenses: Lilly; Travel / Accommodation / Expenses: Novartis. A. Redondo: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy: Clovis; Research grant / Funding (institution): Eisai. C. Valverde: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Research grant / Funding (institution): Bluprint; Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (institution): Karyopharm; Research grant / Funding (institution): Decyphera; Research grant / Funding (institution): Incyte. A. Lopez Pousa: Travel / Accommodation / Expenses: PharmaMar. S. Stacchiotti: Research grant / Funding (institution): Pfizer . E. Palmerini: Advisory / Consultancy, Research grant / Funding (institution): Daiichi Sankyo; Advisory / Consultancy: Amgen; Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Research grant / Funding (institution): Bristol-Myers Squibb (BMS); Research grant / Funding (institution): Pfizer; Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Travel / Accommodation / Expenses: Takeda. D.S. Moura: Research grant / Funding (institution),
v684 | Sarcoma
Travel / Accommodation / Expenses: PharmaMar; Research grant / Funding (institution), Travel / Accommodation / Expenses: Eisai; Research grant / Funding (institution): Novartis. L. D’Ambrosio: Travel / Accommodation / Expenses: PharmaMar; Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy: PSI. J.A. Lopez Martin: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Celgene; Advisory / Consultancy: Novartis; Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties: PharmaMar; Advisory / Consultancy: Chobani; Advisory / Consultancy: Pfizer. All other authors have declared no conflicts of interest.
1670O
ADP-A2M4 (MAGE-A4) in patients with synovial sarcoma
B.A. Van Tine1, M.O. Butler2, D. Araujo3, M.L. Johnson4, J. Clarke5, D. Liebner6, K. Odunsi7, A.J. Olszanski8, S. Basu9, F. Brophy10, T. Holdich11, T. Trivedi10, R.G. Amado10, D.S. Hong12 1 Department of Medical Oncology and Hematology, Washington University School of Medicine, St. Louis, MO, USA, 2Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, ON, Canada, 3Sarcoma Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA, 4Medical Oncology, Sarah Cannon Research Institute-Cancer Centre, Nashville, TN, USA, 5Department of Medicine, Division of Medical Oncology, Duke University School of Medicine, Durham, NC, USA, 6Internal Medicine, Ohio State University, Columbus, OH, USA, 7Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, USA, 8Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA, 9Translational Sciences, Adaptimmune, Philadelphia, PA, USA, 10 Clinical Development, Adaptimmune, Philadelphia, PA, USA, 11Clinical Development, Adaptimmune Ltd, Abingdon, UK, 12Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA Background: This study (NCT03132922) evaluates safety, tolerability, and antitumor activity of ADP-A2M4, genetically engineered autologous specific peptide enhanced affinity receptor (SPEAR) T-cells directed towards a MAGE-A4 peptide expressed in the context of HLA-A*02. Here, we report on a subset of patients (pts) with synovial sarcoma (SS). Methods: In this first-in-human T-cell dose-escalation study, pts who are HLA-A*02þ (excluding *02:05, *02:07), have inoperable or metastatic MAGE-A4þ disease, and meet entry criteria are eligible for treatment. Following apheresis, T-cells are isolated, transduced with MAGE-A4c1032TCR, and expanded. The lymphodepletion chemotherapy increased in intensity as the study progressed, with max dose of 30 mg/m2/d fludarabine x 4 d and 1800 mg/m2/d cyclophosphamide x 2 d. During dose escalation, 3 pts with various tumor types received 0.1x109 (620%), 1x109 (range: 0.5 – 1.2 109), or 5x109 (range: 1.2 – 6 109) transduced cells and were monitored for dose-limiting toxicities (DLTs). During expansion, 30 pts (not only SS) will be treated with 1.2 – 10 x 109 transduced cells. Disease is assessed per RECIST by CT/MRI at wk 6, 12, 18, and 24, and every 3 mo for 2 yr, then every 6 mo or until progression. Correlative studies will investigate transduced cell persistence, phenotype, and function, and serum and tumor microenvironment factors. Results: No DLTs were reported. ADP-A2M4 was well tolerated, with adverse events consistent with chemotherapy or other immunotherapies. 10 pts with SS have been treated in cohort 3 and the expansion phase (30Apr19). Median T-cell dose was 9.7 x 109 (4.49 - 9.98 x 109). 8 pts have post-baseline tumor assessments. There are 3 confirmed partial responses (PR) (-86%, -44%, -54), and 1 unconfirmed PR (-31%) at wk 6. Best response was stable disease in 3 pts (-27% and -15%, ongoing, and þ12%, progressed) and progressive disease in 1. 2 pts have yet to be assessed. Ex vivo analysis of transduced cells from peripheral blood and tumor showed cells were cytolytic and activated in an antigen-specific manner. Conclusions: ADP-A2M4 induced clinical responses in pts with SS. Transduced T-cells expand upon exposure to antigen and are functional. Updated data from this ongoing study will be presented. Clinical trial identification: NCT03132922, First posted on April 28, 2017. Editorial acknowledgement: Debra Brocksmith, MB ChB, PhD, of Envision Pharma Group; contracted by Adaptimmune. Legal entity responsible for the study: Adaptimmune. Funding: Adaptimmune. Disclosure: B.A. Van Tine: Research grant / Funding (self): Pfizer; Research grant / Funding (self): Tracon; Research grant / Funding (self): Merck; Advisory / Consultancy: Epizyme; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy: CytRX; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen; Advisory / Consultancy: Immune Design; Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: Plexxicon; Advisory / Consultancy: Adaptimmune; Speaker Bureau / Expert testimony: Caris. M.O. Butler: Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Merck; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self): Roche; Advisory / Consultancy: Adaptimmune; Advisory / Consultancy: EMD Serono; Advisory / Consultancy: GSK; Advisory / Consultancy: Immunocore; Advisory / Consultancy: Immunovaccine; Research grant / Funding (institution): Takara Bio. M.L. Johnson: Research grant / Funding (institution): BerGenBio; Research grant / Funding (institution): Lilly; Research grant / Funding (institution), Travel / Accommodation / Expenses: EMD Serono; Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): Mirati Therapeutics; Research grant / Funding (institution): Genmab; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research
Volume 30 | Supplement 5 | October 2019
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J. Martin Broto1, N. Hindi1, G.E. Grignani2, J. Martinez Trufero3, A. Redondo4, C. Valverde5, A. Lopez Pousa6, S. Stacchiotti7, E. Palmerini8, E. de Alava9, D.S. Moura10, H. Perez Vega11, P. Collini12, I. Otero13, P. Ledesma14, E. Marchesi15, L. D’Ambrosio2, J.A. Lopez Martin13 1 Instituto de Biomedicina de Sevilla, Seville, Spain, Hospital Universitario Virgen del Rocio, Seville, Spain, 2Medical Oncology, Istituto di Candiolo - FPO - IRCCS, Candiolo, Italy, 3Dept. Medical Oncology, Hospital Miguel Servet, Zaragoza, Spain, 4Dept. Oncologia Medica, Hospital Universitario La Paz, Madrid, Spain, 5Medical Oncology Dept., Vall d’Hebron University Hospital, Barcelona, Spain, 6Medical Oncology Dept., Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, 7Adult Mesenchymal Tumor Medical Oncology Unit, Dept. Cancer Medicine, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, Milan, Italy, 8Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy, 9Dept. Pathology, Hospital Universitario Virgen del Rocio, Seville, Spain, 10 Advanced Therapies and Biomarkers in Oncology Group, Instituto de Biomedicina de Sevilla, Seville, Spain, 11Radiology, Hospital Universitario Virgen del Rocio, Seville, Spain, 12 Department of Diagnostic Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, 13Medical Oncology, Hospital Universitario Doce de Octubrerio Doce de Octubre, Madrid, Spain, 14Clinical Research, Sofpromed, Palma de Mallorca, Spain, 15Clinical Research, Italian Sarcoma Group, Bologna, Italy
Annals of Oncology
abstracts
Annals of Oncology 1671O
Assessment of cardiotoxicity (CT) associated with doxorubicin (dox) in patients (pts) with advanced soft tissue sarcoma (STS) in a phase III randomized trial
R.L. Jones1, A. Wagner2, A. Kawai3, A. Shahir4, V. Soldatenkova5, J. Wright6, W.D. Tap7 Medical Oncology, Royal Marsden Hospital NHS Foundation Trust, London, UK, 2 Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA, 3Musculoskeletal Oncology Dept., National Cancer Center Hospital, Tokyo, Japan, 4Medical Oncology, Eli Lilly and Company, Erl Wood, UK, 5Medical Oncology, Eli Lilly and Company, Indianapolis, IN, USA, 6Medical Oncology, Eli Lilly and Company, Indianapolis, IN, USA, 7 Sarcoma Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA 1
Background: The ANNOUNCE trial evaluated the efficacy of the anti-PDGFR alpha antibody olaratumab þ dox versus placebo þ dox in adults with STS. CT was a secondary safety objective. Methods: Treatment included dox 75mg/m2 on Day 1 of a 21-day cycle for up to 8 cycles, with olaratumab/placebo on Days 1, 8 until progression. Use of the cardioprotectant dexrazoxane was allowed with any cycle and recommended with Cycle 5 and beyond. Pts were monitored for left ventricular ejection fraction (LVEF) decreases after 4, 6, 8 cycles and electrocardiogram (ECG) changes in cycles 1 to 9; both were then monitored every 3 months for 1 year, every 6 months for 1 year, then annually. Eligible pts had a LVEF of 50% at baseline, and were without QTc prolongation, active symptoms of cardiac arrhythmia/dysfunction, and prior anthracycline exposure or mediastinal/pericardial radiation. Results: Median age was 57 years. Medical history included cardiac disorders (n ¼ 33; 6.5%) and ECG abnormalities (n ¼ 1; 0.2%). Of the 506 treated pts from both arms, 504 (99.6%) had at least 1 dox dose, of which, 64.0% received at least 1 dose of dexrazoxane, with 61.0% of these pts starting before Cycle 6. Median dox exposure was 6 cycles/450mg/m2; median duration of CT evaluation was 28 weeks. One pt died due to acute cardiac failure after a cumulative dox dose of 441mg/m2. Adverse events (AEs) of cardiac dysfunction/decreased LVEF are summarized (Table). ECG abnormalities considered AEs occurred in 15 (3.0%) pts. Conclusions: The ANNOUNCE trial prospectively evaluated CT in a large cohort of dox-treated adults with STS, most of whom received dexrazoxane for cardioprotection. Although LVEF decreases were common with routine monitoring, symptomatic cardiac dysfunction was reported infrequently. Frequency of CT was similar in both arms. Longer safety follow-up may be warranted to determine the true rate of CT with higher cumulative doses of dox. Clinical trial identification: NCT02451943. Editorial acknowledgement: Karen Paulsrud, RPh, with Eli Lilly and Company, provided medical writing support. Legal entity responsible for the study: Eli Lilly and Company. Funding: Eli Lilly and Company. Disclosure: R.L. Jones: Advisory / Consultancy: Adaptimmune; Advisory / Consultancy: Blueprint; Advisory / Consultancy: Clinigen; Advisory / Consultancy: Eisai; Advisory / Consultancy: Epizyme; Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: Deciphera; Advisory / Consultancy: Immune Design; Advisory / Consultancy: Eli Lilly and Company; Advisory / Consultancy: Merck; Advisory / Consultancy: PharmaMar; Advisory / Consultancy: Tracon. A.J. Wagner: Advisory /
Volume 30 | Supplement 5 | October 2019
doi:10.1093/annonc/mdz283 | v685
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grant / Funding (institution), Travel / Accommodation / Expenses, Additional travel from: Astellas, AstraZeneca, Boehringer Ingelheim, Clovis, Daiichi Sankyo, Bristol-Myers Squibb, Exelixis, Incyte, Merck, Sysmex Inostics, Vapotherm: Genentech; Research grant / Funding (institution): Stemcentrix; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Checkpoint Therapeutics; Research grant / Funding (institution): Array Biopharma; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): Apexigen; Research grant / Funding (institution), Travel / Accommodation / Expenses: AbbVie; Research grant / Funding (institution): Tarveda; Research grant / Funding (institution): Adaptimmune; Research grant / Funding (institution), Additional advisory for: Gelgene, Boehringer Ingelheim, Sanofi, LOXO, Calithera, Merck, Araxes Pharma, Mersana Therapeutics, BeiGene, Incyte, Guardant Health, Bristol-Myers Squibb, Ribon Therapeutics: Syndax; Research grant / Funding (institution), Additional grant funding from: Boehringer Ingelheim, Sanofi, Hengrui Therapuetics INC, Merck, Daiichi-Sankyo, Lycera, G1 Therapeutics, Dynavax, LOXO, Cytomx, BeiGene, Birdie, Corvus, Incyte, Genocea, Gritstone, Amgen, Bristol-Myers Squibb, Kadmon, Clovis, Acerta, OncoMed, Guardant Health, Takeda, Shattuck Labs, GSK: Neovia. J. Clarke: Research grant / Funding (self): MedPacto; Research grant / Funding (self): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (self): Eli Lilly; Research grant / Funding (self): Genentech; Research grant / Funding (self): Spectrum; Research grant / Funding (self): Adaptimmune; Research grant / Funding (self): Bayer; Research grant / Funding (self): AbbVie; Research grant / Funding (self): Moderna; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Guardant; Advisory / Consultancy: AstraZeneca. D. Liebner: Advisory / Consultancy: Foundation Medicine; Advisory / Consultancy: Blueprint Medicines. K. Odunsi: Research grant / Funding (self): ITeos Therapeutics. A.J. Olszanski: Advisory / Consultancy, Research grant / Funding (self): BristolMyers Squibb; Advisory / Consultancy: Merck; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Array; Advisory / Consultancy, Research grant / Funding (self): EMD Serono; Advisory / Consultancy: Iovance; Advisory / Consultancy: Novartis; Advisory / Consultancy, Research grant / Funding (self): Alkermes; Research grant / Funding (self): Adaptimmune; Research grant / Funding (self): Astellas; Research grant / Funding (self): Boston Biomedical; Research grant / Funding (self): Checkmate Pharmaceutics; Research grant / Funding (self): GSK; Research grant / Funding (self): Immunocore; Research grant / Funding (self): Intensity Therapeutics; Research grant / Funding (self): Kartos; Research grant / Funding (self): Kura; Research grant / Funding (self): Oncoceutics; Research grant / Funding (self): Targovax. S. Basu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Adaptimmune. F. Brophy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Adaptimmune. T. Holdich: Shareholder / Stockholder / Stock options, Full / Part-time employment: Adaptimmune. T. Trivedi: Shareholder / Stockholder / Stock options, Full / Part-time employment: Adaptimmune. R.G. Amado: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Adaptimmune. D.S. Hong: Research grant / Funding (self): AbbVie; Advisory / Consultancy, Research grant / Funding (self): Adaptimmune; Research grant / Funding (self): Amgen; Research grant / Funding (self): AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): Bayer; Research grant / Funding (self): Bristol-Myers Squibb; Research grant / Funding (self): Daiichi-Sankyo; Research grant / Funding (self): Eisai; Research grant / Funding (self): Fate Therapeutics; Advisory / Consultancy, Research grant / Funding (self): Genentech; Research grant / Funding (self), Travel / Accommodation / Expenses: Genmab; Research grant / Funding (self): Ignyta; Advisory / Consultancy, Research grant / Funding (self): Infinity; Research grant / Funding (self): Kite; Research grant / Funding (self): Kyowa; Research grant / Funding (self): Lilly; Research grant / Funding (self), Travel / Accommodation / Expenses: LOXO; Research grant / Funding (self): MedImmune; Research grant / Funding (self): Merck; Research grant / Funding (self), Additional grant funding from: miRNA, Molecular Templates, Mologen, NCI-CTEP, Novartics, Pfizer, Seattle Genetics, Takeda. Additional advisory consulting for: Alpha Insights, Axiom, Baxter, GLG, Group H, Guidepoint Global, Merrimack, Medscape, Numab, Pfizer, Seattle Genetics, Takeda, Trieza Therapeutics, WebMD; Travel support from MiRNA, AACR, ASCO, SITC; ownership interests in Molecular Match, OncoResponse, Presagia Inc: Mirati. All other authors have declared no conflicts of interest.