- Email: [email protected]
Results of the NLG2105 Phase I Trial Using the IDO Pathway Inhibitor Indoximod, in Combination with Radiation and Chemotherapy, for Children with Newly Diagnosed DIPG
abstracts
Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pierre Fabre; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bioncotech; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Regeneron; Advisory / Consultancy, Research grant / Funding (institution): Incyte; Non-remunerated activity/ies: Biosequence; Research grant / Funding (institution): Idera. P. Lopez-Casas: Full / Part-time employment: Bioncotech. M. Martin: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Puma; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Advisory / Consultancy: Tahio; Advisory / Consultancy: Pharmamar; Advisory / Consultancy: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Daiichi. D. Tersago: Full / Part-time employment: Bioncotech. M. Quintero: Full / Part-time employment, Officer / Board of Directors: Bioncotech. I. Melero: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Alligator; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy: Merck-Serono; Advisory / Consultancy: Genentech; Advisory / Consultancy: Genmab; Advisory / Consultancy: Incyte; Advisory / Consultancy: Tusk; Advisory / Consultancy: Numab; Advisory / Consultancy: Molecular Partners; Advisory / Consultancy: F Star; Advisory / Consultancy: Bayer; Advisory / Consultancy: AstraZeneca. All other authors have declared no conflicts of interest.
determined recommended phase-II dose (RP2D), and the study design called for phase I monitoring to confirm safety of this dose in DIPG patients. Results: Thirteen children (median age 9 years, range 5 to 20 years) with newly diagnosed DIPG were treated using this indoximod-based radio-chemo-immunotherapy regimen. The 12-month OS was 62% (8/13) and estimated median OS was 14.5 months (follow-up range 4.8 to 22 months) with 4 patients remaining in follow-up. This compares favorably to the expected 12-month OS of approximately 45% and median OS of approximately 10.8 months from published historical controls (Kilburn, et al; 2017). Two patients experienced near-complete responses until showing relapse at 7.6 months and 13.3 months of study therapy. Patients were followed with quantitative volumetric analyses of MRIs and serial measurements of peripheral blood inflammatory monocytes, T cell activation, and pro-inflammatory cytokines. The most common adverse events attributed to indoximod were thrombocytopenia, diarrhea, nausea, vomiting, and fatigue. Conclusion: Adding indoximod-based immunotherapy to conventional radiation and chemotherapy for up-front therapy of children with DIPG appears to be well tolerated with improved outcomes. Clinical trial identification: NLG2105, NCT02502708. Legal entity responsible for the study: NewLink Genetics Corporation. Funding: NewLink Genetics Corporation, Alex’s Lemonade Stand Foundation, Cannonball Kids cancer Foundation, Beloco Foundation, Eli’s Block Party Foundation, Hyundai Hope on Wheels Foundation, Northern Nevada Children’s Cancer Research Foundation, CAM Fund, Press On Foundation. Disclosure: T.S. Johnson: Research grant / Funding (institution): NewLink Genetics Corporation. E.P. Kennedy: Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: NewLink Genetics Corporation. N. Vahanian: Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: NewLink Genetics Corporation. D.H. Munn: Advisory / Consultancy, Shareholder / Stockholder / Stock options, Licensing / Royalties: NewLink Genetics Corporation. All other authors have declared no conflicts of interest.
102P 101P
Results of the NLG2105 phase I trial using the IDO pathway inhibitor indoximod, in combination with radiation and chemotherapy, for children with newly diagnosed DIPG
T.S. Johnson1, D. Aguilera2, A. Al-Basheer3, Z. Berrong4, R.C. Castellino2, B.R. Eaton5, N. Esiashvili5, N. Foreman6, I.M. Heger7, E.P. Kennedy8, N. Vahanian8, W. Martin3, R. Pacholczyk4, E. Ring1, R.F. Sadek9, A. Smith10, M. Shimoda4, T.J. Macdonald2, D.H. Munn1 1 Georgia Cancer Center and Department of Pediatrics, Augusta University, Augusta, GA, USA, 2Aflac Cancer & Blood Disorders Center at Children’s Healthcare of Atlanta and Department of Pediatrics, Emory University, Atlanta, GA, USA, 3Georgia Cancer Center and Department of Radiation Oncology, Augusta University, Augusta, GA, USA, 4 Georgia Cancer Center, Augusta University, Augusta, GA, USA, 5Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA, USA, 6 Department of Pediatrics, Children’s Hospital Colorado, Aurora, CO, USA, 7Pediatric Neurosurgery Program, Medical City Children’s Hospital, Dallas, TX, USA, 8NewLink Genetics Corporation, NewLink Genetics Corporation, Ames, IA, USA, 9Georgia Cancer Center and Department of Population Health Sciences, Augusta University, Augusta, GA, USA, 10Department of Pediatrics, Arnold Palmer Hospital for Children, Orlando, AL, USA Background: We conducted a phase Ib dose-confirmation study of indoximod with radiation, followed by indoximod with cyclic temozolomide therapy, to evaluate safety and overall survival (OS) in children with newly diagnosed DIPG (diffuse intrinsic pontine glioma). Indoximod is a small-molecule inhibitor of the IDO pathway that reverses immune suppression imposed by tumor microenvironments. DIPG is a uniformly fatal orphan disease with no curative treatment options. Methods: Children age 3 to 21 years, with newly diagnosed DIPG were eligible for treatment with oral indoximod (38.4 mg/kg/day divided BID, throughout) combined with fractionated conformal radiation therapy (54 Gy in 30 fractions), followed by cyclic oral chemo-immunotherapy using indoximod combined with temozolomide (200 mg/ m2/day, days 1-5 of each 28-day cycle). The indoximod dose was the previously
xi38 | Therapeutic Development
Results from a phase II trial of pembrolizumab (P) plus gemcitabine (Gem) in patients (pts) with HER2-negative advanced breast cancer (ABC): GEICAM/2015-04 (PANGEA-Breast) study
L. de la Cruz Merino1, J. Cruz2, J.L. Alonso3, V. Quiroga Garcia4, F. Moreno Anton5, R. Andres6, M. Santiesteban7, M. Ramos Vazquez8, M. Gion Cortes9, J. Corte´s10, N. Palazon Carrion11, I. Ceballos Lenza12, A. Soto13, M. Casas14, S. Benito15, S. Bezares Montes16, E. Holgado17 1 Medical Oncology, Hospital Universitario Virgen Macarena, Seville, Spain, 2Medical Oncology, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain, 3Medical Oncology, IMIB-Hospital Clınico Universitario Virgen de la Arrixaca, Murcia, Spain, 4 Medical Oncology, Badalona Applied Research Group in Oncology (B-ARGO Group), Catalan Institute of Oncology (ICO Badalona), Hospital Germans Trias i Pujol, Badalona, Spain, 5Medical Oncology, Hospital Clinico Universitario San Carlos, Madrid, Spain, 6Medical Oncology, Hospital Clinico Universitario Lozano Blesa, Zaragoza, Spain, 7 Medical Oncology, Clınica Universidad de Navarra, Pamplona, Spain, 8Medical Oncology, Centro Oncologico de Galicia, A Coru~ na, Spain, 9Medical Oncology, Hospital Universitario Ramon y Cajal, Madrid, Spain, 10Medical Oncology, IOB Institute of Oncology; Vall dHebron Institute of Oncology, Barcelona, Spain, 11Clinical Oncology, Hospital Universitario Virgen Macarena, Seville, Spain, 12Oncology, Hospital Universitario de Canarias, San Cristobal De La Laguna, Spain, 13Medical Oncology, Hospital Clinico Universitario Virgen de la Arrixaca, El Palmar, Spain, 14Statistics, GEICAM Spanish Breast Cancer Group, San Sebastian De Los Reyes, Spain, 15Clinical Operations, GEICAM-Spanish Breast Cancer Research Group, San Sebastian De Los Reyes, Spain, 16Scientific Department, GEICAM, San Sebastian De Los Reyes, Madrid, Spain, 17Medical Oncolgoy, IOB Institute of Oncology, Hospital Ruber Juan Bravo, Madrid, Spain Background: This trial is based on a combination strategy with two immunostimulatory agents in the search of synergism that may induce responses with long-term clinical benefit in ABC pts. Safety data from the run-in-phase were published in ESMO IO 2018. Here, we report the results from the phase II part of the study. Methods: HER2-negative ABC pts previously treated with anthracyclines and taxanes (unless contraindicated), 4 chemotherapy lines and/or 2 hormone therapy lines,
Volume 30 | Supplement 11 | December 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_11/mdz451.010/5675198 by Vanderbilt Univ Library user on 31 December 2019
Conclusion: BO-112 combined with anti PD-1 shows a manageable safety profile, direct antitumor effects and innate and adaptive immune system activation. Efficacy analyses suggest potential to reverse primary resistance to anti-PD1 treatment. Studies in other indications, including combination with radiotherapy, are planned. Clinical trial identification: NCT02828098. Legal entity responsible for the study: Bioncotech Therapeutics. Funding: Bioncotech Therapeutics. Disclosure: I. Marquez-Rodas: Advisory / Consultancy, Research grant / Funding (institution),
Annals of Oncology
Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pierre Fabre; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bioncotech; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Regeneron; Advisory / Consultancy, Research grant / Funding (institution): Incyte; Non-remunerated activity/ies: Biosequence; Research grant / Funding (institution): Idera. P. Lopez-Casas: Full / Part-time employment: Bioncotech. M. Martin: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Puma; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Advisory / Consultancy: Tahio; Advisory / Consultancy: Pharmamar; Advisory / Consultancy: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Daiichi. D. Tersago: Full / Part-time employment: Bioncotech. M. Quintero: Full / Part-time employment, Officer / Board of Directors: Bioncotech. I. Melero: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Alligator; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy: Merck-Serono; Advisory / Consultancy: Genentech; Advisory / Consultancy: Genmab; Advisory / Consultancy: Incyte; Advisory / Consultancy: Tusk; Advisory / Consultancy: Numab; Advisory / Consultancy: Molecular Partners; Advisory / Consultancy: F Star; Advisory / Consultancy: Bayer; Advisory / Consultancy: AstraZeneca. All other authors have declared no conflicts of interest.
determined recommended phase-II dose (RP2D), and the study design called for phase I monitoring to confirm safety of this dose in DIPG patients. Results: Thirteen children (median age 9 years, range 5 to 20 years) with newly diagnosed DIPG were treated using this indoximod-based radio-chemo-immunotherapy regimen. The 12-month OS was 62% (8/13) and estimated median OS was 14.5 months (follow-up range 4.8 to 22 months) with 4 patients remaining in follow-up. This compares favorably to the expected 12-month OS of approximately 45% and median OS of approximately 10.8 months from published historical controls (Kilburn, et al; 2017). Two patients experienced near-complete responses until showing relapse at 7.6 months and 13.3 months of study therapy. Patients were followed with quantitative volumetric analyses of MRIs and serial measurements of peripheral blood inflammatory monocytes, T cell activation, and pro-inflammatory cytokines. The most common adverse events attributed to indoximod were thrombocytopenia, diarrhea, nausea, vomiting, and fatigue. Conclusion: Adding indoximod-based immunotherapy to conventional radiation and chemotherapy for up-front therapy of children with DIPG appears to be well tolerated with improved outcomes. Clinical trial identification: NLG2105, NCT02502708. Legal entity responsible for the study: NewLink Genetics Corporation. Funding: NewLink Genetics Corporation, Alex’s Lemonade Stand Foundation, Cannonball Kids cancer Foundation, Beloco Foundation, Eli’s Block Party Foundation, Hyundai Hope on Wheels Foundation, Northern Nevada Children’s Cancer Research Foundation, CAM Fund, Press On Foundation. Disclosure: T.S. Johnson: Research grant / Funding (institution): NewLink Genetics Corporation. E.P. Kennedy: Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: NewLink Genetics Corporation. N. Vahanian: Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: NewLink Genetics Corporation. D.H. Munn: Advisory / Consultancy, Shareholder / Stockholder / Stock options, Licensing / Royalties: NewLink Genetics Corporation. All other authors have declared no conflicts of interest.
102P 101P
Results of the NLG2105 phase I trial using the IDO pathway inhibitor indoximod, in combination with radiation and chemotherapy, for children with newly diagnosed DIPG
T.S. Johnson1, D. Aguilera2, A. Al-Basheer3, Z. Berrong4, R.C. Castellino2, B.R. Eaton5, N. Esiashvili5, N. Foreman6, I.M. Heger7, E.P. Kennedy8, N. Vahanian8, W. Martin3, R. Pacholczyk4, E. Ring1, R.F. Sadek9, A. Smith10, M. Shimoda4, T.J. Macdonald2, D.H. Munn1 1 Georgia Cancer Center and Department of Pediatrics, Augusta University, Augusta, GA, USA, 2Aflac Cancer & Blood Disorders Center at Children’s Healthcare of Atlanta and Department of Pediatrics, Emory University, Atlanta, GA, USA, 3Georgia Cancer Center and Department of Radiation Oncology, Augusta University, Augusta, GA, USA, 4 Georgia Cancer Center, Augusta University, Augusta, GA, USA, 5Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA, USA, 6 Department of Pediatrics, Children’s Hospital Colorado, Aurora, CO, USA, 7Pediatric Neurosurgery Program, Medical City Children’s Hospital, Dallas, TX, USA, 8NewLink Genetics Corporation, NewLink Genetics Corporation, Ames, IA, USA, 9Georgia Cancer Center and Department of Population Health Sciences, Augusta University, Augusta, GA, USA, 10Department of Pediatrics, Arnold Palmer Hospital for Children, Orlando, AL, USA Background: We conducted a phase Ib dose-confirmation study of indoximod with radiation, followed by indoximod with cyclic temozolomide therapy, to evaluate safety and overall survival (OS) in children with newly diagnosed DIPG (diffuse intrinsic pontine glioma). Indoximod is a small-molecule inhibitor of the IDO pathway that reverses immune suppression imposed by tumor microenvironments. DIPG is a uniformly fatal orphan disease with no curative treatment options. Methods: Children age 3 to 21 years, with newly diagnosed DIPG were eligible for treatment with oral indoximod (38.4 mg/kg/day divided BID, throughout) combined with fractionated conformal radiation therapy (54 Gy in 30 fractions), followed by cyclic oral chemo-immunotherapy using indoximod combined with temozolomide (200 mg/ m2/day, days 1-5 of each 28-day cycle). The indoximod dose was the previously
xi38 | Therapeutic Development
Results from a phase II trial of pembrolizumab (P) plus gemcitabine (Gem) in patients (pts) with HER2-negative advanced breast cancer (ABC): GEICAM/2015-04 (PANGEA-Breast) study
L. de la Cruz Merino1, J. Cruz2, J.L. Alonso3, V. Quiroga Garcia4, F. Moreno Anton5, R. Andres6, M. Santiesteban7, M. Ramos Vazquez8, M. Gion Cortes9, J. Corte´s10, N. Palazon Carrion11, I. Ceballos Lenza12, A. Soto13, M. Casas14, S. Benito15, S. Bezares Montes16, E. Holgado17 1 Medical Oncology, Hospital Universitario Virgen Macarena, Seville, Spain, 2Medical Oncology, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain, 3Medical Oncology, IMIB-Hospital Clınico Universitario Virgen de la Arrixaca, Murcia, Spain, 4 Medical Oncology, Badalona Applied Research Group in Oncology (B-ARGO Group), Catalan Institute of Oncology (ICO Badalona), Hospital Germans Trias i Pujol, Badalona, Spain, 5Medical Oncology, Hospital Clinico Universitario San Carlos, Madrid, Spain, 6Medical Oncology, Hospital Clinico Universitario Lozano Blesa, Zaragoza, Spain, 7 Medical Oncology, Clınica Universidad de Navarra, Pamplona, Spain, 8Medical Oncology, Centro Oncologico de Galicia, A Coru~ na, Spain, 9Medical Oncology, Hospital Universitario Ramon y Cajal, Madrid, Spain, 10Medical Oncology, IOB Institute of Oncology; Vall dHebron Institute of Oncology, Barcelona, Spain, 11Clinical Oncology, Hospital Universitario Virgen Macarena, Seville, Spain, 12Oncology, Hospital Universitario de Canarias, San Cristobal De La Laguna, Spain, 13Medical Oncology, Hospital Clinico Universitario Virgen de la Arrixaca, El Palmar, Spain, 14Statistics, GEICAM Spanish Breast Cancer Group, San Sebastian De Los Reyes, Spain, 15Clinical Operations, GEICAM-Spanish Breast Cancer Research Group, San Sebastian De Los Reyes, Spain, 16Scientific Department, GEICAM, San Sebastian De Los Reyes, Madrid, Spain, 17Medical Oncolgoy, IOB Institute of Oncology, Hospital Ruber Juan Bravo, Madrid, Spain Background: This trial is based on a combination strategy with two immunostimulatory agents in the search of synergism that may induce responses with long-term clinical benefit in ABC pts. Safety data from the run-in-phase were published in ESMO IO 2018. Here, we report the results from the phase II part of the study. Methods: HER2-negative ABC pts previously treated with anthracyclines and taxanes (unless contraindicated), 4 chemotherapy lines and/or 2 hormone therapy lines,
Volume 30 | Supplement 11 | December 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_11/mdz451.010/5675198 by Vanderbilt Univ Library user on 31 December 2019
Conclusion: BO-112 combined with anti PD-1 shows a manageable safety profile, direct antitumor effects and innate and adaptive immune system activation. Efficacy analyses suggest potential to reverse primary resistance to anti-PD1 treatment. Studies in other indications, including combination with radiotherapy, are planned. Clinical trial identification: NCT02828098. Legal entity responsible for the study: Bioncotech Therapeutics. Funding: Bioncotech Therapeutics. Disclosure: I. Marquez-Rodas: Advisory / Consultancy, Research grant / Funding (institution),
Annals of Oncology