- Email: [email protected]
PD) exposure-response characterization of GSK3359609 (GSK609) from INDUCE-1, a phase I open-label study
abstracts
Annals of Oncology 1971P
Pharmacokinetic/ pharmacodynamic (PK/PD) exposure-response characterization of GSK3359609 (GSK609) from INDUCE-1, a phase I open-label study
Background: GSK609 an agonist non-T cell depleting IgG4 monoclonal antibody (mAb) against inducible co-stimulatory receptor (ICOS) exhibits T cell mediated immune stimulating and anti-tumor activity. INDUCE-1 is the first in human study investigating GSK609 alone and in combinations which include pembrolizumab in select tumor types including recurrent/metastatic (R/M) HNSCC. Methods: Safety, PK, PD, and preliminary antitumor activity of GSK609 are being evaluated at doses from 0.001 to 10 mg/kg every 3 weeks (Q3W). Blood samples collected prior to dosing and on-study are evaluated for PK and PD effects on lymphocytes and ICOS receptor occupancy (RO). Tumor biopsies at Screening and Week 6 are evaluated for changes in tumor immune infiltrates (TIL) by a multiplexed immuno-fluorescence and gene expression platforms. Results: The GSK609 PK disposition shows low clearance, limited central volume of distribution, and mean systemic half-life of 19 days which is consistent with other humanized mAbs. Evidence of target engagement and tumor size reduction are observed in a R/M HNSCC expansion cohort (EC) at 0.3 mg/kg with 200 mg pembrolizumab. Dose and concentration-RO analyses suggest 0.1 mg/kg GSK609 maintains 70% RO on peripheral CD4þ and CD8þ T cells. Quantitative TIL evaluation of paired tumor biopsies demonstrates favorable immune microenvironment in the tumor at exposures observed in patients treated with 0.3mg/kg. TIL and tumor-based gene expression data demonstrate non-linear, dose-dependent changes in select immune activation markers. Exposure-response assessments reveal no difference in baseline-toWeek 9 target lesion change across exposures in the EC. Furthermore, cross-cohort pooled exposure-response analysis of Grade 2 AEs demonstrates similar safety outcomes across the exposures/doses. Additionally, population PK modeling suggests comparable exposures can be maintained by fixed dosing as well. Conclusions: The current data provide preliminary evidence of GSK609 target engagement and biological activity at clinically tolerable doses and support further exploration of the 0.3mg/kg or 24mg fixed dose. Clinical trial identification: NCT02723955 (Rel. 31March2016). Legal entity responsible for the study: GlaxoSmithKline. Funding: GlaxoSmithKline. Disclosure: M. Maio: Honoraria (self): BMS, MSD, Roche, Merck, Eli Lilly; Honoraria (institution), Patients’ fee to the University Hospital of Siena: BMS, MSD, AZ, Roche, Merck; Advisory / Consultancy: BMS, MSD, Roche, Merck, Eli Lilly; Travel / Accommodation / Expenses: BMS, MSD, Roche, Merck, Eli Lilly; Non-remunerated activity/ies, Press conferences: Merck, BMS. T. Bauer: Advisory / Consultancy, Self: Guardant Health; Loxo; Pfizer; Advisory / Consultancy, Institution: Ignyta; Moderna Therapeutics; Pfizer; Speaker Bureau / Expert testimony, Self: Bayer; Research grant / Funding (institution): Daiichi Sankyo; Medpacto, Inc.; Incyte; Mirati Therapeutics; MedImmune; Abbvie; AstraZeneca; Leap Therapeutics; MabVax; Stemline Therapeutics; Merck; Lilly; GlaxoSmithKline; Novartis, Pfizer; Genentech/Roche; Deciphera; Merrimack; Immunogen; Millennium; I; Travel / Accommodation / Expenses: Astellas Pharma; AstraZeneca; Celgene; Clovis Oncology; EMD Serono; Genentech; Lilly; Merck; Novartis; Pharmacyclics; Sysmex. D. Rischin: Advisory / Consultancy, All uncompensated : MSD, Regeneron, GSK, BMS; Research grant / Funding (institution): Regeneron, Roche, MSD, GSK, BMS; Travel / Accommodation / Expenses: MSD. V. Moreno: Advisory / Consultancy: Merck, BMS; Travel / Accommodation / Expenses: Regeneron/ Sanofi, BMS. J.M. Trigo Perez: Advisory / Consultancy: Regeneron/Sanofi, BMS; Speaker Bureau / Expert testimony: Regeneron/Sanofi, BMS; Travel / Accommodation / Expenses: Regeneron/Sanofi, BMS. M. Chisamore: Full / Part-time employment: Merck & Co. Inc; Shareholder / Stockholder / Stock options: Merck & Co. Inc. J. Sadik Shaik: Full / Part-time employment: GlaxoSmithKline; Shareholder / Stockholder / Stock options: GlaxoSmithKline. F. Rigat: Full / Part-time employment: GlaxoSmithKline; Shareholder / Stockholder / Stock options: GlaxoSmithKline. C. Ellis: Full / Parttime employment: GlaxoSmithKline; Shareholder / Stockholder / Stock options: GlaxoSmithKline. H. Chen: Full / Part-time employment: GlaxoSmithKline; Shareholder / Stockholder / Stock options: GlaxoSmithKline. R. Gagnon: Full / Part-time employment: GlaxoSmithKline; Shareholder / Stockholder / Stock options: GlaxoSmithKline. S. Scherer: Full / Part-time employment: GlaxoSmithKline; Shareholder / Stockholder / Stock options: GlaxoSmithKline. D. Turner: Full / Part-time employment: GlaxoSmithKline; Shareholder / Stockholder / Stock options: GlaxoSmithKline. S. Yadavilli: Full / Part-time employment: GlaxoSmithKline; Shareholder / Stockholder / Stock options: GlaxoSmithKline. M. Ballas: Full / Part-time employment: GlaxoSmithKline; Shareholder / Stockholder / Stock options: GlaxoSmithKline. A. Hoos: Full / Parttime employment: GlaxoSmithKline; Shareholder / Stockholder / Stock options: GlaxoSmithKline. E. Angevin: Advisory / Consultancy: Merck Sharp & Dohme, GlaxoSmithKline, Celgene Research, MedImmune; Travel / Accommodation / Expenses: AbbVie, Roche, Sanofi, Pfizer, MedImmune, Innate Pharma, Celgene, BMS; Research grant / Funding (institution): Abbvie, Aduro, Agios, Amgen,
Volume 30 | Supplement 5 | October 2019
1972P
In vitro functional interrogation of viable circulating tumor associated cells (C-TACs) for evaluating platin resistance
S. Schuster, D. Akolkar, S. Patil, D. Patil, V. Datta, A. Srinivasan, R. Datar Research and Innovations, Datar Cancer Genetics Limited, Nasik, India
1
Background: Platins are used extensively to treat Solid Organ Cancers like Ovarian, Breast, Colorectal, Lung, Pancreatic and Bladder Cancer. Eventually however, most cancer patients develop resistance to these treatments. As presently, no assay is available to non-invasively determine the onset of resistance to platinum drugs, the lethal evolution is usually silent. We show that apoptosis resistant Circulating Tumor Associated Cells (C-TACs) can be isolated and functionally interrogated in vitro to determine response / resistance to Platins in real time by chemo-sensitivity. Methods: We evaluated the chemo-sensitivity / resistance profile of C-TACs obtained from 256 patients with confirmed diagnosis of Breast, Ovarian, Colorectal, Pancreatic, or Lung cancer; 207 (80.8%) patients were refractory to Platins, 49 (19.2%) were treatment naı¨ve and 36 (14.0%) of C-TAC samples were compared with corresponding Tumor Derived Cells (TDCs). Results: Out of 256 samples of venous blood examined, more than 5000 C-TACs could be harvested in 244 (95.0%) samples. 182 (88.0%) samples from the refractory cohort showed chemo resistance to Platins, 16 (34.0%) of samples from treatment naı¨ve samples showed Platin resistance and 29 (85.2%) concurrently analyzed C-TAC samples showed chemo resistance to Platins corresponding to identical resistance in TDCs. Conclusions: Functional interrogation of C-TACs by in vitro chemo-sensitivity analysis provides an accurate non-invasive method to determine Platin resistance in solid organ cancers. Legal entity responsible for the study: The authors. Funding: Datar Cancer Genetics Limited. Disclosure: S. Schuster: Full / Part-time employment: Datar Cancer Genetics Limited. D. Akolkar: Full / Part-time employment: Datar Cancer Genetics Limited. S. Patil: Full / Part-time employment: Datar Cancer Genetics Limited. D. Patil: Full / Part-time employment: Datar Cancer Genetics Limited. V. Datta: Full / Part-time employment: Datar Cancer Genetics Limited. A. Srinivasan: Full / Part-time employment: Datar Cancer Genetics Limited. R. Datar: Officer / Board of Directors: Datar Cancer Genetics Limited.
1973P
Targeting ARG2 as a novel therapeutic approach for cancer
M.M. Grzybowski, J. Pe˛czkowicz-Szyszka, P. Wolska, P.S. Sta nczak, M. Welzer, E. Nikolaev, A.M. Siwi nska, R. Błaszczyk, B. Borek, M. Dzie˛gielewski, A. Gzik, J. Nowicka, J. Brzezi nska, K. Je˛drzejczak, J. Chrzanowski, A. Gołe˛biowski, J. Olczak, K. Dzwonek, P. Dobrza nski Department of Biology, OncoArendi Therapeutics SA, Warsaw, Poland Background: Immunotherapies are considered the most promising therapeutic approach for cancer and the immunosuppressive activity of ARG1 has been recognized as an important mechanism of the tumor immune evasion. This prompted the development of arginase inhibitors, which in preclinical models, enhanced antitumor immunity as a monotherapy and in combination with other immune checkpoint inhibitors. On the other hand, ARG2, but not ARG1, is highly expressed in neoplastic cells in many tumors and its expression is correlated with malignant phenotype. Preclinical studies confirmed that ARG2 promotes the proliferation of cancer cells and the growth of tumor xenografts independently of its immunosuppressive activity. Generation of polyamines to facilitate the growth of hypoxic and nutrient-deprived tumors, as well as specific metabolic adaptations including increased reliance on protein catabolism are the major mechanisms underlying the tumorigenic activity of ARG2. Hence, the tumor cell intrinsic activity of ARG2 represents an attractive intracellular target for novel therapies with arginase inhibitors. Methods: The compound activity was determined using human ARG1 and ARG2, and in CHO-K cells expressing ARG1 and ARG2. ARG1 and ARG2 expression in cancer cell lines and dissected tumors was assessed by WB and qPCR. CellTiter-Glo was used to assess the antiproliferative activity of the compound. In vivo antitumor activity was evaluated in murine CT26 (syngeneic) and human K562 (xenograft) subcutaneous mouse models. Results: The expression of the endogenous ARG2 was confirmed in multiple human cancer cell lines and xenografts. We developed a highly potent dual ARG1 and ARG2 inhibitor, OATD-02, with a good cellular activity. We demonstrated that OATD-02 inhibited proliferation of multiple human cancer cell lines expressing ARG2 and suppressed the growth of human xenografts. OATD-02 also strongly inhibited the growth of the syngeneic CT26 tumors. Conclusions: OATD-02, a potent ARG1 and ARG2 inhibitor, exerts its antitumor efficacy not only by the reactivation of the immune response but also by directly suppressing the ARG2-dependent proliferation of cancerous cells. Thus, OATD-02 is a very promising compound for the treatment of hypoxic tumors which are particularly resistant to therapies.
doi:10.1093/annonc/mdz268 | v793
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz268.098/5577190 by guest on 24 October 2019
M. Maio1, S.L. Groenland2, T. Bauer3, D. Rischin4, I. Gardeazabal5, V. Moreno6, J.M. Trigo Perez7, M. Chisamore8, J. Sadik Shaik9, F. Rigat10, C. Ellis11, H. Chen12, R. Gagnon12, S. Scherer13, D. Turner9, S. Yadavilli13, M. Ballas11, A. Hoos11, E. Angevin14 1 Center for Immuno-Oncology, Instituto Toscano Tumori, Azienda Ospedaliera Universitaria Senese - Santa Maria delle Scotte, Siena, Italy, 2Pharmacy & Pharmacology Department, Netherlands Cancer Institute/Antoni van Leeuwenhoek hospital (NKI-AVL), Amsterdam, Netherlands, 3Hematology/Oncology, Sarah Cannon Research Institute, Nashville, TN, USA, 4Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia, 5Medical Oncology Dept., Vall d’Hebron University Hospital, Barcelona, Spain, 6Clinical Research Phase 1 Trials Unit, START Madrid-FJD, Madrid, Spain, 7Medical Oncology, Hospital Universitario Virgen de la Victoria, Malaga, Spain, 8Oncology Early Clinical Development, Merck Sharp & Dohme Corp. USA, Whitehouse Station, NJ, USA, 9Clinical Pharmacology, GlaxoSmithKline, Collegeville, PA, USA, 10Clinical Statistics, GlaxoSmithKline, Stevenage, UK, 11Oncology Clinical Development, GlaxoSmithKline USA, Collegeville, PA, USA, 12 Clinical Statistics, GlaxoSmithKline, Collegeville, PA, USA, 13Clinical Biomarkers, GlaxoSmithKline USA, Collegeville, PA, USA, 14Drug Development Department (DITEP), Gustave Roussy - Cancer Campus, Villejuif, France
Argen-x, Astex, AstraZeneca, Aveo pharmaceuticals, Bayer, Beigene, Blueprint, BMS, Boeringer Ingelheim, Celgene, Chugai, Clovis, Daiichi Sankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, Gamamabs, Genentech, Gortec, GSK, H3 bio. All other authors have declared no conflicts of interest.
Annals of Oncology 1971P
Pharmacokinetic/ pharmacodynamic (PK/PD) exposure-response characterization of GSK3359609 (GSK609) from INDUCE-1, a phase I open-label study
Background: GSK609 an agonist non-T cell depleting IgG4 monoclonal antibody (mAb) against inducible co-stimulatory receptor (ICOS) exhibits T cell mediated immune stimulating and anti-tumor activity. INDUCE-1 is the first in human study investigating GSK609 alone and in combinations which include pembrolizumab in select tumor types including recurrent/metastatic (R/M) HNSCC. Methods: Safety, PK, PD, and preliminary antitumor activity of GSK609 are being evaluated at doses from 0.001 to 10 mg/kg every 3 weeks (Q3W). Blood samples collected prior to dosing and on-study are evaluated for PK and PD effects on lymphocytes and ICOS receptor occupancy (RO). Tumor biopsies at Screening and Week 6 are evaluated for changes in tumor immune infiltrates (TIL) by a multiplexed immuno-fluorescence and gene expression platforms. Results: The GSK609 PK disposition shows low clearance, limited central volume of distribution, and mean systemic half-life of 19 days which is consistent with other humanized mAbs. Evidence of target engagement and tumor size reduction are observed in a R/M HNSCC expansion cohort (EC) at 0.3 mg/kg with 200 mg pembrolizumab. Dose and concentration-RO analyses suggest 0.1 mg/kg GSK609 maintains 70% RO on peripheral CD4þ and CD8þ T cells. Quantitative TIL evaluation of paired tumor biopsies demonstrates favorable immune microenvironment in the tumor at exposures observed in patients treated with 0.3mg/kg. TIL and tumor-based gene expression data demonstrate non-linear, dose-dependent changes in select immune activation markers. Exposure-response assessments reveal no difference in baseline-toWeek 9 target lesion change across exposures in the EC. Furthermore, cross-cohort pooled exposure-response analysis of Grade 2 AEs demonstrates similar safety outcomes across the exposures/doses. Additionally, population PK modeling suggests comparable exposures can be maintained by fixed dosing as well. Conclusions: The current data provide preliminary evidence of GSK609 target engagement and biological activity at clinically tolerable doses and support further exploration of the 0.3mg/kg or 24mg fixed dose. Clinical trial identification: NCT02723955 (Rel. 31March2016). Legal entity responsible for the study: GlaxoSmithKline. Funding: GlaxoSmithKline. Disclosure: M. Maio: Honoraria (self): BMS, MSD, Roche, Merck, Eli Lilly; Honoraria (institution), Patients’ fee to the University Hospital of Siena: BMS, MSD, AZ, Roche, Merck; Advisory / Consultancy: BMS, MSD, Roche, Merck, Eli Lilly; Travel / Accommodation / Expenses: BMS, MSD, Roche, Merck, Eli Lilly; Non-remunerated activity/ies, Press conferences: Merck, BMS. T. Bauer: Advisory / Consultancy, Self: Guardant Health; Loxo; Pfizer; Advisory / Consultancy, Institution: Ignyta; Moderna Therapeutics; Pfizer; Speaker Bureau / Expert testimony, Self: Bayer; Research grant / Funding (institution): Daiichi Sankyo; Medpacto, Inc.; Incyte; Mirati Therapeutics; MedImmune; Abbvie; AstraZeneca; Leap Therapeutics; MabVax; Stemline Therapeutics; Merck; Lilly; GlaxoSmithKline; Novartis, Pfizer; Genentech/Roche; Deciphera; Merrimack; Immunogen; Millennium; I; Travel / Accommodation / Expenses: Astellas Pharma; AstraZeneca; Celgene; Clovis Oncology; EMD Serono; Genentech; Lilly; Merck; Novartis; Pharmacyclics; Sysmex. D. Rischin: Advisory / Consultancy, All uncompensated : MSD, Regeneron, GSK, BMS; Research grant / Funding (institution): Regeneron, Roche, MSD, GSK, BMS; Travel / Accommodation / Expenses: MSD. V. Moreno: Advisory / Consultancy: Merck, BMS; Travel / Accommodation / Expenses: Regeneron/ Sanofi, BMS. J.M. Trigo Perez: Advisory / Consultancy: Regeneron/Sanofi, BMS; Speaker Bureau / Expert testimony: Regeneron/Sanofi, BMS; Travel / Accommodation / Expenses: Regeneron/Sanofi, BMS. M. Chisamore: Full / Part-time employment: Merck & Co. Inc; Shareholder / Stockholder / Stock options: Merck & Co. Inc. J. Sadik Shaik: Full / Part-time employment: GlaxoSmithKline; Shareholder / Stockholder / Stock options: GlaxoSmithKline. F. Rigat: Full / Part-time employment: GlaxoSmithKline; Shareholder / Stockholder / Stock options: GlaxoSmithKline. C. Ellis: Full / Parttime employment: GlaxoSmithKline; Shareholder / Stockholder / Stock options: GlaxoSmithKline. H. Chen: Full / Part-time employment: GlaxoSmithKline; Shareholder / Stockholder / Stock options: GlaxoSmithKline. R. Gagnon: Full / Part-time employment: GlaxoSmithKline; Shareholder / Stockholder / Stock options: GlaxoSmithKline. S. Scherer: Full / Part-time employment: GlaxoSmithKline; Shareholder / Stockholder / Stock options: GlaxoSmithKline. D. Turner: Full / Part-time employment: GlaxoSmithKline; Shareholder / Stockholder / Stock options: GlaxoSmithKline. S. Yadavilli: Full / Part-time employment: GlaxoSmithKline; Shareholder / Stockholder / Stock options: GlaxoSmithKline. M. Ballas: Full / Part-time employment: GlaxoSmithKline; Shareholder / Stockholder / Stock options: GlaxoSmithKline. A. Hoos: Full / Parttime employment: GlaxoSmithKline; Shareholder / Stockholder / Stock options: GlaxoSmithKline. E. Angevin: Advisory / Consultancy: Merck Sharp & Dohme, GlaxoSmithKline, Celgene Research, MedImmune; Travel / Accommodation / Expenses: AbbVie, Roche, Sanofi, Pfizer, MedImmune, Innate Pharma, Celgene, BMS; Research grant / Funding (institution): Abbvie, Aduro, Agios, Amgen,
Volume 30 | Supplement 5 | October 2019
1972P
In vitro functional interrogation of viable circulating tumor associated cells (C-TACs) for evaluating platin resistance
S. Schuster, D. Akolkar, S. Patil, D. Patil, V. Datta, A. Srinivasan, R. Datar Research and Innovations, Datar Cancer Genetics Limited, Nasik, India
1
Background: Platins are used extensively to treat Solid Organ Cancers like Ovarian, Breast, Colorectal, Lung, Pancreatic and Bladder Cancer. Eventually however, most cancer patients develop resistance to these treatments. As presently, no assay is available to non-invasively determine the onset of resistance to platinum drugs, the lethal evolution is usually silent. We show that apoptosis resistant Circulating Tumor Associated Cells (C-TACs) can be isolated and functionally interrogated in vitro to determine response / resistance to Platins in real time by chemo-sensitivity. Methods: We evaluated the chemo-sensitivity / resistance profile of C-TACs obtained from 256 patients with confirmed diagnosis of Breast, Ovarian, Colorectal, Pancreatic, or Lung cancer; 207 (80.8%) patients were refractory to Platins, 49 (19.2%) were treatment naı¨ve and 36 (14.0%) of C-TAC samples were compared with corresponding Tumor Derived Cells (TDCs). Results: Out of 256 samples of venous blood examined, more than 5000 C-TACs could be harvested in 244 (95.0%) samples. 182 (88.0%) samples from the refractory cohort showed chemo resistance to Platins, 16 (34.0%) of samples from treatment naı¨ve samples showed Platin resistance and 29 (85.2%) concurrently analyzed C-TAC samples showed chemo resistance to Platins corresponding to identical resistance in TDCs. Conclusions: Functional interrogation of C-TACs by in vitro chemo-sensitivity analysis provides an accurate non-invasive method to determine Platin resistance in solid organ cancers. Legal entity responsible for the study: The authors. Funding: Datar Cancer Genetics Limited. Disclosure: S. Schuster: Full / Part-time employment: Datar Cancer Genetics Limited. D. Akolkar: Full / Part-time employment: Datar Cancer Genetics Limited. S. Patil: Full / Part-time employment: Datar Cancer Genetics Limited. D. Patil: Full / Part-time employment: Datar Cancer Genetics Limited. V. Datta: Full / Part-time employment: Datar Cancer Genetics Limited. A. Srinivasan: Full / Part-time employment: Datar Cancer Genetics Limited. R. Datar: Officer / Board of Directors: Datar Cancer Genetics Limited.
1973P
Targeting ARG2 as a novel therapeutic approach for cancer
M.M. Grzybowski, J. Pe˛czkowicz-Szyszka, P. Wolska, P.S. Sta nczak, M. Welzer, E. Nikolaev, A.M. Siwi nska, R. Błaszczyk, B. Borek, M. Dzie˛gielewski, A. Gzik, J. Nowicka, J. Brzezi nska, K. Je˛drzejczak, J. Chrzanowski, A. Gołe˛biowski, J. Olczak, K. Dzwonek, P. Dobrza nski Department of Biology, OncoArendi Therapeutics SA, Warsaw, Poland Background: Immunotherapies are considered the most promising therapeutic approach for cancer and the immunosuppressive activity of ARG1 has been recognized as an important mechanism of the tumor immune evasion. This prompted the development of arginase inhibitors, which in preclinical models, enhanced antitumor immunity as a monotherapy and in combination with other immune checkpoint inhibitors. On the other hand, ARG2, but not ARG1, is highly expressed in neoplastic cells in many tumors and its expression is correlated with malignant phenotype. Preclinical studies confirmed that ARG2 promotes the proliferation of cancer cells and the growth of tumor xenografts independently of its immunosuppressive activity. Generation of polyamines to facilitate the growth of hypoxic and nutrient-deprived tumors, as well as specific metabolic adaptations including increased reliance on protein catabolism are the major mechanisms underlying the tumorigenic activity of ARG2. Hence, the tumor cell intrinsic activity of ARG2 represents an attractive intracellular target for novel therapies with arginase inhibitors. Methods: The compound activity was determined using human ARG1 and ARG2, and in CHO-K cells expressing ARG1 and ARG2. ARG1 and ARG2 expression in cancer cell lines and dissected tumors was assessed by WB and qPCR. CellTiter-Glo was used to assess the antiproliferative activity of the compound. In vivo antitumor activity was evaluated in murine CT26 (syngeneic) and human K562 (xenograft) subcutaneous mouse models. Results: The expression of the endogenous ARG2 was confirmed in multiple human cancer cell lines and xenografts. We developed a highly potent dual ARG1 and ARG2 inhibitor, OATD-02, with a good cellular activity. We demonstrated that OATD-02 inhibited proliferation of multiple human cancer cell lines expressing ARG2 and suppressed the growth of human xenografts. OATD-02 also strongly inhibited the growth of the syngeneic CT26 tumors. Conclusions: OATD-02, a potent ARG1 and ARG2 inhibitor, exerts its antitumor efficacy not only by the reactivation of the immune response but also by directly suppressing the ARG2-dependent proliferation of cancerous cells. Thus, OATD-02 is a very promising compound for the treatment of hypoxic tumors which are particularly resistant to therapies.
doi:10.1093/annonc/mdz268 | v793
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz268.098/5577190 by guest on 24 October 2019
M. Maio1, S.L. Groenland2, T. Bauer3, D. Rischin4, I. Gardeazabal5, V. Moreno6, J.M. Trigo Perez7, M. Chisamore8, J. Sadik Shaik9, F. Rigat10, C. Ellis11, H. Chen12, R. Gagnon12, S. Scherer13, D. Turner9, S. Yadavilli13, M. Ballas11, A. Hoos11, E. Angevin14 1 Center for Immuno-Oncology, Instituto Toscano Tumori, Azienda Ospedaliera Universitaria Senese - Santa Maria delle Scotte, Siena, Italy, 2Pharmacy & Pharmacology Department, Netherlands Cancer Institute/Antoni van Leeuwenhoek hospital (NKI-AVL), Amsterdam, Netherlands, 3Hematology/Oncology, Sarah Cannon Research Institute, Nashville, TN, USA, 4Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia, 5Medical Oncology Dept., Vall d’Hebron University Hospital, Barcelona, Spain, 6Clinical Research Phase 1 Trials Unit, START Madrid-FJD, Madrid, Spain, 7Medical Oncology, Hospital Universitario Virgen de la Victoria, Malaga, Spain, 8Oncology Early Clinical Development, Merck Sharp & Dohme Corp. USA, Whitehouse Station, NJ, USA, 9Clinical Pharmacology, GlaxoSmithKline, Collegeville, PA, USA, 10Clinical Statistics, GlaxoSmithKline, Stevenage, UK, 11Oncology Clinical Development, GlaxoSmithKline USA, Collegeville, PA, USA, 12 Clinical Statistics, GlaxoSmithKline, Collegeville, PA, USA, 13Clinical Biomarkers, GlaxoSmithKline USA, Collegeville, PA, USA, 14Drug Development Department (DITEP), Gustave Roussy - Cancer Campus, Villejuif, France
Argen-x, Astex, AstraZeneca, Aveo pharmaceuticals, Bayer, Beigene, Blueprint, BMS, Boeringer Ingelheim, Celgene, Chugai, Clovis, Daiichi Sankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, Gamamabs, Genentech, Gortec, GSK, H3 bio. All other authors have declared no conflicts of interest.