{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T16:32:35Z","timestamp":1783355555101,"version":"3.54.6"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T00:00:00Z","timestamp":1656460800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T00:00:00Z","timestamp":1656460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100016957","name":"Mirati Therapeutics, Inc.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100016957","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Invest New Drugs"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Sitravatinib (MGCD516), a spectrum-selective receptor tyrosine kinase inhibitor targeting <jats:italic>TAM<\/jats:italic> (<jats:italic>TYRO3<\/jats:italic>, <jats:italic>AXL<\/jats:italic>, <jats:italic>MERTK<\/jats:italic>) and split kinase family receptors, has demonstrated preclinical anti-tumor activity and modulation of tumor microenvironment. This first-in-human phase 1\/1b study included sitravatinib dose exploration and anti-tumor activity evaluation in selected patients with advanced solid tumors. Primary objectives included assessment of safety, pharmacokinetics and clinical activity of sitravatinib. Secondary objectives included identifying doses for further investigation and exploring molecular markers for patient selection. In phase 1, 32 patients received 10\u2013200 mg, while phase 1b dose expansion comprised 161 patients (150 mg n = 99, 120 mg n = 62). Maximum tolerated dose was determined as 150 mg daily. Dose-limiting toxicity was reported in 4\/28 evaluable phase 1 patients (three at 200 mg, one at 80 mg). In phase 1b, 120 mg was defined as the recommended dose due to tolerability. Treatment-related adverse events (TRAEs) were experienced by 174\/193 patients (90.2%); grade \u2265 3 TRAEs in 103 patients (53.4%). Most common TRAEs were diarrhea, fatigue, hypertension and nausea; TRAEs led to treatment discontinuation in 26 patients (13.5%) and death in one patient. Sitravatinib was steadily absorbed and declined from plasma with a terminal elimination half-life of 42.1\u201351.5 h following oral administration. Overall objective response rate was 11.8% in phase 1b, 13.2% in patients with non-small cell lung cancer (NSCLC) and 4.2% in patients with NSCLC with prior checkpoint inhibitor experience. Sitravatinib demonstrated manageable safety and modest clinical activity in solid tumors. NCT02219711 (first posted August 14, 2014).<\/jats:p>","DOI":"10.1007\/s10637-022-01274-y","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T14:04:47Z","timestamp":1656511487000},"page":"990-1000","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["First-in-human phase 1\/1b study to evaluate sitravatinib in patients with advanced solid tumors"],"prefix":"10.1007","volume":"40","author":[{"given":"Todd","family":"Bauer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byong Chul","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Heist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyudmila","family":"Bazhenova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Werner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Goel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Wan","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Adkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D.","family":"Carvajal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajjai","family":"Alva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Eaton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Christensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia","family":"Neuteboom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Chao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubham","family":"Pant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,29]]},"reference":[{"key":"1274_CR1","doi-asserted-by":"publisher","first-page":"3491","DOI":"10.3390\/ijms19113491","volume":"19","author":"T Yamaoka","year":"2018","unstructured":"Yamaoka T, Kusumoto S, Ando K, Ohba M, Ohmori T (2018) Receptor tyrosine kinase-targeted cancer therapy. Int J Mol Sci 19:3491. https:\/\/doi.org\/10.3390\/ijms19113491","journal-title":"Int J Mol Sci"},{"key":"1274_CR2","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1111\/imr.12522","volume":"276","author":"YT Akalu","year":"2017","unstructured":"Akalu YT, Rothlin CV, Ghosh S (2017) TAM receptor tyrosine kinases as emerging targets of innate immune checkpoint blockade for cancer therapy. Immunol Rev 276:165\u2013177. https:\/\/doi.org\/10.1111\/imr.12522","journal-title":"Immunol Rev"},{"key":"1274_CR3","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1038\/nrc3627","volume":"13","author":"HL Goel","year":"2013","unstructured":"Goel HL, Mercurio AM (2013) VEGF targets the tumour cell. Nat Rev Cancer 13:871\u2013882. https:\/\/doi.org\/10.1038\/nrc3627","journal-title":"Nat Rev Cancer"},{"key":"1274_CR4","doi-asserted-by":"publisher","first-page":"4093","DOI":"10.18632\/oncotarget.6547","volume":"7","author":"PP Patwardhan","year":"2016","unstructured":"Patwardhan PP, Ivy KS, Musi E, de Stanchina E, Schwartz GK (2016) Significant blockade of multiple receptor tyrosine kinases by MGCD516 (sitravatinib), a novel small molecule inhibitor, shows potent anti-tumor activity in preclinical models of sarcoma. Oncotarget 7:4093\u20134109. https:\/\/doi.org\/10.18632\/oncotarget.6547","journal-title":"Oncotarget"},{"key":"1274_CR5","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.124184","volume":"3","author":"W Du","year":"2018","unstructured":"Du W, Huang H, Sorrelle N, Brekken RA (2018) Sitravatinib potentiates immune checkpoint blockade in refractory cancer models. JCI Insight 3:e124184. https:\/\/doi.org\/10.1172\/jci.insight.124184","journal-title":"JCI Insight"},{"key":"1274_CR6","unstructured":"Clinicaltrials.gov (2020) Phase 1\/1b Study of MGCD516 in Patients With Advanced Cancer. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02219711. Updated January 30, 2020. Accessed October 21, 2021"},{"key":"1274_CR7","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.1200\/jco.2012.45.7903","volume":"31","author":"Y Ji","year":"2013","unstructured":"Ji Y, Wang S-J (2013) Modified toxicity probability interval design: a safer and more reliable method than the 3 + 3 design for practical phase I trials. J Clin Oncol 31:1785\u20131791. https:\/\/doi.org\/10.1200\/jco.2012.45.7903","journal-title":"J Clin Oncol"},{"key":"1274_CR8","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/1479-5876-5-32","volume":"5","author":"SE DePrimo","year":"2007","unstructured":"DePrimo SE, Bello CL, Smeraglia J, Baum CM, Spinella D, Rini BI et al (2007) Circulating protein biomarkers of pharmacodynamic activity of sunitinib in patients with metastatic renal cell carcinoma: modulation of VEGF and VEGF-related proteins. J Transl Med 5:32. https:\/\/doi.org\/10.1186\/1479-5876-5-32","journal-title":"J Transl Med"},{"key":"1274_CR9","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1007\/s00280-015-2779-7","volume":"76","author":"JY Bruce","year":"2015","unstructured":"Bruce JY, Scully PC, Carmichael LL, Eickhoff JC, Perlman SB, Kolesar JM et al (2015) Pharmacodynamic study of axitinib in patients with advanced malignancies assessed with (18)F-3\u2019deoxy-3\u2019fluoro-L-thymidine positron emission tomography\/computed tomography. Cancer Chemother Pharmacol 76:187\u2013195. https:\/\/doi.org\/10.1007\/s00280-015-2779-7","journal-title":"Cancer Chemother Pharmacol"},{"key":"1274_CR10","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s12967-015-0747-y","volume":"14","author":"R Leibowitz-Amit","year":"2016","unstructured":"Leibowitz-Amit R, Pintilie M, Khoja L, Azad AA, Berger R, Laird AD et al (2016) Changes in plasma biomarkers following treatment with cabozantinib in metastatic castration-resistant prostate cancer: a post hoc analysis of an extension cohort of a phase II trial. J Transl Med 14:12. https:\/\/doi.org\/10.1186\/s12967-015-0747-y","journal-title":"J Transl Med"},{"key":"1274_CR11","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1056\/NEJMoa2005653","volume":"383","author":"A Drilon","year":"2020","unstructured":"Drilon A, Oxnard GR, Tan DSW, Loong HHF, Johnson M, Gainor J et al (2020) Efficacy of selpercatinib in RET fusion\u2013positive non\u2013small-cell lung cancer. N Engl J Med 383:813\u2013824. https:\/\/doi.org\/10.1056\/NEJMoa2005653","journal-title":"N Engl J Med"},{"key":"1274_CR12","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1056\/NEJMoa2004407","volume":"383","author":"PK Paik","year":"2020","unstructured":"Paik PK, Felip E, Veillon R, Sakai H, Cortot AB, Garassino MC et al (2020) Tepotinib in non\u2013small-cell lung cancer with MET exon 14 skipping mutations. N Engl J Med 383:931\u2013943. https:\/\/doi.org\/10.1056\/NEJMoa2004407","journal-title":"N Engl J Med"},{"key":"1274_CR13","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.3390\/cancers13061195","volume":"13","author":"P Aehnlich","year":"2021","unstructured":"Aehnlich P, Powell RM, Peeters MJW, Rahbech A, thor Straten P (2021) TAM receptor inhibition\u2013implications for cancer and the immune system. Cancers (Basel) 13:1195. https:\/\/doi.org\/10.3390\/cancers13061195","journal-title":"Cancers (Basel)"},{"key":"1274_CR14","doi-asserted-by":"publisher","first-page":"978","DOI":"10.3389\/fimmu.2018.00978","volume":"9","author":"J Yang","year":"2018","unstructured":"Yang J, Yan J, Liu B (2018) Targeting VEGF\/VEGFR to modulate antitumor immunity. Front Immunol 9:978. https:\/\/doi.org\/10.3389\/fimmu.2018.00978","journal-title":"Front Immunol"},{"key":"1274_CR15","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003476","volume":"9","author":"M Oliva","year":"2021","unstructured":"Oliva M, Chepeha D, Araujo DV, Diaz-Mejia JJ, Olson P, Prawira A et al (2021) Antitumor immune effects of preoperative sitravatinib and nivolumab in oral cavity cancer: SNOW window-of-opportunity study. J Immunother Cancer 9:e003476. https:\/\/doi.org\/10.1136\/jitc-2021-003476","journal-title":"J Immunother Cancer"},{"key":"1274_CR16","doi-asserted-by":"publisher","first-page":"6569","DOI":"10.1200\/JCO.2020.38.15_suppl.6569","volume":"38","author":"M Oliva","year":"2020","unstructured":"Oliva M, Araujo DV, Chepeha DB, Prawira A, Spreafico A, Bratman SV et al (2020) SNOW: sitravatinib and nivolumab in oral cavity cancer (OCC) window of opportunity study. J Immunother Cancer 38:6569\u20136569. https:\/\/doi.org\/10.1200\/JCO.2020.38.15_suppl.6569","journal-title":"J Immunother Cancer"},{"issue":"suppl_5","key":"1274_CR17","doi-asserted-by":"publisher","first-page":"S949","DOI":"10.1016\/j.annonc.2021.08.1796","volume":"32","author":"TA Leal","year":"2021","unstructured":"Leal TA, Berz D, Rybkin I, Iams WT, Bruno D, Blakely C et al (2021) 11910 \u2013 MRTX-500: phase II trial of sitravatinib (sitra) + nivolumab (nivo) in patients (pts) with non-squamous (NSQ) non-small cell lung cancer (NSCLC) progressing on or after prior checkpoint inhibitor (CPI) therapy. Ann Oncol 32(suppl_5):S949\u2013S1039","journal-title":"Ann Oncol"},{"key":"1274_CR18","unstructured":"Clinicaltrials.gov (2021) Phase 3 Study of Sitravatinib Plus Nivolumab vs Docetaxel in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer (SAPPHIRE). https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03906071. Updated September 30, 2021. Accessed October 21, 2021"},{"key":"1274_CR19","unstructured":"Clinicaltrials.gov (2021) Tislelizumab in Combination With Sitravatinib in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04921358. Updated September 21, 2021. Accessed October 21, 2021."}],"container-title":["Investigational New Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10637-022-01274-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10637-022-01274-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10637-022-01274-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,11]],"date-time":"2023-03-11T04:49:08Z","timestamp":1678510148000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10637-022-01274-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,29]]},"references-count":19,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["1274"],"URL":"https:\/\/doi.org\/10.1007\/s10637-022-01274-y","relation":{},"ISSN":["0167-6997","1573-0646"],"issn-type":[{"value":"0167-6997","type":"print"},{"value":"1573-0646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,29]]},"assertion":[{"value":"20 April 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 June 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 June 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by an institutional review board at each participating site and was conducted in accordance with Good Clinical Practice guidelines, defined by the International Conference on Harmonisation. All patients provided written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics statement"}},{"value":"TMB declares Consulting or advisory role: Guardant Health, Loxo, Pfizer, Exelixis, Blueprint Medicines, Foundation Medicine, Bayer, AstraZeneca; Consulting or advisory role to institution: Ignyta, Moderna Therapeutics, Pfizer; Speakers\u2019 bureau: Bayer, Bristol-Myers Squibb, Eli Lilly; Research funding to institution: Daiichi Sankyo, Medpacto, Inc., Incyte, Mirati Therapeutics, Inc., MedImmune, Abbvie, AstraZeneca, Leap Therapeutics, MabVax, Stemline Therapeutics, Merck, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, Genentech\/Roche, Deciphera, Merrimack, Immunogen, Millennium, Ignyta, Calithera Biosciences, Kolltan Pharmaceuticals, Principa Biopharma, Peleton, Immunocore, Roche, Aileron Therapeutics, Bristol-Myers Squibb, Amgen, Moderna Therapeutics, Sanofi, Boehringer Ingelheim, Astellas Pharma, Five Prime Therapeutics, Jacobio, Top Alliance BioScience, Loxo, Janssen, Clovis Oncology, Takeda, Karyopharm Therapeutics, Onyx, Phosplatin Therapeutics, Foundation Medicine, ARMO BioSciences; Travel, accommodation, expenses: Astellas Pharma, AstraZeneca, Celgene, Clovis Oncology, EMD Serono, Genentech, Eli Lilly, Merck, Novartis, Pharmacyclics, Sysmex, Pfizer BCC declares Research funding: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, Abbvie, Medpacto, GIInnovation, Eli Lilly, Blueprint Medicines, Interpark Bio Convergence Corp.; Consulting role: Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Bristol Myers Squibb, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint Medicines; Stock ownership: TheraCanVac Inc., Gencurix Inc., Bridgebio Therapeutics, KANAPH Therapeutic Inc., Cyrus Therapeutics, Interpark Bio Convergence Corp.; Scientific Advisory Board: KANAPH Therapeutic Inc., Brigebio Therapeutics, Cyrus Therapeutics, Guardant Health, Joseah BIO; Board of director: Gencurix Inc., Interpark Bio Convergence Corp.; Royalty: Champions Oncology; Founder: DAAN Biotherapeutics. RH declares Consulting: Abbvie, Novartis, EMD Serono, Daichii Sankyo; Research funding to institution, not to self: Abbvie, Agios, Corvus, Daichii Sankyo, Exelixis, Mirati Therapeutics, Inc., Novartis, Eli Lilly, Turning Point. LB declares Data Monitoring Committee: ORIC; Advisory board: Turning Point Therapeutics, Daichi, Bristol Myers Squibb, Janssen, Merck, Regeneron, Bayer, Takeda, Boehringer Ingleheim, Novartis, Genentech and Sanofi; Scientific committee: Neuvogen; Research funding to institution: Beyondspring. TLW declares research funding to institution from: AbbVie, AstraZeneca, Clovis Oncology, Genmab, GlaxoSmithKline-Tesaro, Mersana, Repare, Roche-Genentech. SG was funded by Mirati Therapeutics, Inc. to conduct this trial (to the institution). DWK declares research funding to institution from: Alpha Biopharma, Amgen, AstraZeneca\/MedImmune, Boehringer Ingelheim, Bridge BioTherapeutics, Chong Keun Dang, Daiichi-Sankyo, GlaxoSmithKline, Hanmi, Janssen, Merus, Mirati Therapeutics, Inc., MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche\/Genentech, Takeda, Turning Point Therapeutics, Xcovery, Yuhan; Travel and accommodation support for advisory board meeting attendance from: Amgen, Daiichi-Sankyo. DA declares Consulting or scientific advisory board support: Vaccinex, Merck, Blueprint Medicines, Boehringer Ingelheim, Cue Biopharma, Kura Oncology, Eisai, Exelixus, twoXAR, Immunitas, Natco Pharma, TargImmune Therapeutics, and Xilio; Institutional research support: Vaccinex, Pfizer, Eli Lilly, Merck, Celgene\/Bristol Myers Squibb, Novartis, AstraZeneca, Atara Bio, Blueprint Medicine, Celldex, Enzychem, Kura, Exelixis, Innate, Sensei, Debiopharm International, ISA Therapeutics, Gilead Sciences, BeiGene, Roche, Hookpia Biotech, Adlai Nortye USA, Rubius Therapeutics, Epizyme, and Matrix Biomed. RDC declares Consulting: Alkermes, Bristol Myers Squibb, Castle Biosciences, Ideaya, Immunocore, InxMed, Iovance, Merck, Novartis, Oncosec, Pierre Fabre, PureTech Health, Regeneron, Sanofi Genzyme, Sorrento Therapeutics, Trisalus; Clinical\/Scientific Advisory Boards: Aura Biosciences, Chimeron, Rgenix; Research Funding to Columbia University: Amgen, Astellis, AstraZeneca, Bristol Myers Squibb, Corvus, Ideaya, Immunocore, Iovance, Merck, Mirati Therapeutics, Inc., Novartis, Pfizer, Plexxikon, Regeneron, Roche\/Genentech. AA declares to be an advisory board member\/consultant for: Merck, Sharp & Dohme Corp, Bristol Myers Squibb, AstraZeneca, Genentech, Roche, Pfizer, Progenics, Prometheus; Travel\/Accommodations\/Expenses: Merck Sharp & Dohme Corp, Bristol Myers Squibb; Research funding through institution: Merck Sharp & Dohme Corp, AstraZeneca, Bristol Myers Squibb, Astellas, Seattle Genetics, Genentech, Pfizer, Progenics, Prometheus, Eli Lilly, ASCO, Celgene, Harpoon Therapeutics. KDE declares research support for clinical trials from Mirati Therapeutics, Inc. JSW declares research funding to institution from: Agenus, AstraZeneca, AstraZeneca\/MedImmune, Bicycle therapeutics, BioNTech, Boehringer Ingelheim, Celgene, CicloMed, Clovis Oncology, Cyteir, Daiichi Sankyo, Genentech\/Roche, GlaxoSmithKline, H3 Biomedicine, Hutchison MediPharma, Ignyta, Jacobio, Janssen Research & Development, Klus Pharma, Kymab, Loxo, LSK BioPharma, Macrogenics, Merck, Moderna Therapeutics, Phoenix Pharmaceuticals, Prelude Therapeutics, QiLu Pharmaceutical, Revolution Medicines, Ribon Therapeutics, Syndax, Stemline Therapeutics, Taiho Pharmaceutical, Tesaro, TopAlliance BioSciences Inc, Xencor, Artios, Erasca, Inc., immuno-Gen, Cullinan Oncology, Immuno-Onc, Bayer Health, Biosplice, Zymeworks, BioTheryX, TeneoBio, Nurix, IgM Biosciences, Aevi Genomic Medicine, PureTech, StingThera, Forty Seven, Treadwell Therapeutics, MabSpace Biosciences, Novartis, Olema Oncology, Seven and Eight Biopharmaceuticals, ORIC Pharmaceuticals, Relay Therapeutics, Black Diamond Therapeutics. YL is a full-time employee of Mirati Therapeutics, Inc. XY is a full-time employee of Mirati Therapeutics, Inc. and owns Mirati stocks. JGC is an employee, shareholder and executive officer at Mirati Therapeutics, Inc. STCN is a former employee of Mirati Therapeutics, Inc. and owns Mirati stocks. RCC is a full-time employee of Mirati Therapeutics, Inc. SP declares Clinical Trials Research (paid to institution) from: Arcus, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Holy Stone Healthcare Co., Tyme, Ipsen, Mirati Therapeutics, Inc., Novartis, Xencor, Astellas, Janssen; Advisory Board\/Consultant: 4D Pharma, Xencor, Ipsen, Zymeworks, Amal Therapeutics, Novartis.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}