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- Myriam Chalabi (Amsterdam, Netherlands)
- Filippo Pietrantonio (Milan, Italy)
LBA24 - KRYSTAL-1: Updated efficacy and safety of adagrasib (MRTX849) with or without cetuximab in patients with advanced colorectal cancer (CRC) harboring a KRASG12C mutation
- Samuel J. Klempner (Boston, United States of America)
Abstract
Background
KRASG12C mutations occur in 3–4% of CRC and are associated with shorter PFS and OS with standard chemotherapy. Adagrasib (ada), a selective and irreversible KRASG12C inhibitor, is optimized for a long half-life (23 h), dose-dependent PK, and CNS penetration. Durable inhibition of KRASG12C may be important in CRC, due to signaling pathways creating susceptibility to feedback reactivation of RAS. Preclinical data suggest dual EGFR/KRASG12C blockade may enhance inhibition of KRAS-dependent signalling and overcome adaptive feedback.
Methods
KRYSTAL-1 (NCT03785249) is a multicohort Ph 1/2 study evaluating safety and efficacy of ada in patients (pts) with KRASG12C-mutated advanced solid tumors. Ada (600 mg BID) and ada + cetuximab (cetux; 400 mg/m2 followed by 250 mg/m2 QW or 500 mg/m2 Q2W) were evaluated in pts with previously treated CRC, in Ph 2 and 1b cohorts, respectively. Responses were investigator assessed.
Results
As of Jun 16 2022, 44 pts received ada and 32 pts received ada + cetux. In the ada mono cohort (median follow-up 20.1 mo), median age was 59 yrs, 50% were female, median prior lines of systemic therapy was 3, 52% and 48% were ECOG PS 0 and 1, respectively. In 43 pts evaluable for efficacy, ORR was 19% (8/43), and DCR was 86% (37/43). Median DOR was 4.3 mo (95% CI 2.3–8.3) and median PFS was 5.6 mo (95% CI 4.1–8.3). In the ada + cetux cohort (median follow-up 17.5 mo), median age was 60 yrs, 53% were female, median prior lines of systemic therapy was 3, 44% and 56% were ECOG PS 0 and 1, respectively. In 28 pts evaluable for efficacy, ORR was 46% (13/28) and DCR was 100% (28/28). Median DOR was 7.6 mo (95% CI 5.7–NE) and median PFS was 6.9 mo (95% CI 5.4–8.1). Gr 1–2 and 3–4 TRAEs occurred in 59% and 34% of pts, respectively, in the ada cohort, and 84% and 16% of pts, respectively, in the ada + cetux cohort. No Gr 5 TRAE occurred.
Conclusions
Adagrasib is well tolerated as monotherapy and with cetuximab. Both showed clinical activity in heavily pretreated pts with KRASG12C-mutated CRC, with more sustained responses with the combination. Adagrasib + cetuximab is being investigated in 2L CRC in the Phase 3 KRYSTAL-10 trial (NCT04793958).
Clinical trial identification
NCT03785249.
Editorial acknowledgement
Third-party medical writing support, under the direction of the authors, was provided by Victoria Eyre-Brook of Ashfield MedComms, an Inizio company, and was funded by Mirati Therapeutics, Inc.
Legal entity responsible for the study
Mirati Therapeutics, Inc.
Funding
Mirati Therapeutics, Inc.
Disclosure
S.J. Klempner: Financial Interests, Personal, Advisory Board, Stomach Cancer Advisory Board: Eli Lilly, Merck, Bristol Myers Squibb, Astellas, Daiichi Sankyo, Pieris; Financial Interests, Personal, Advisory Board, One Time Advisory Board: Natera; Financial Interests, Personal, Advisory Board, Stomach cancer advisory board x 1: Mersana, Sanofi-Aventis; Financial Interests, Personal, Stocks/Shares, Stock Ownership: Turning Point Therapeutics; Financial Interests, Personal, Stocks/Shares, Early investor, company is not public: MBrace; Financial Interests, Institutional, Invited Speaker, National PI for trial: Leap Therapeutics; Financial Interests, Personal and Institutional, Invited Speaker, Local PI for trial, also served on advisory board as noted above: Astellas; Financial Interests, Institutional, Invited Speaker: Macrogenics; Financial Interests, Institutional, Invited Speaker, Trial PI: Silverback; Non-Financial Interests, Advisory Role, Medical-Scientific Advisory Board Member: Debbies Dream Foundation; Non-Financial Interests, Advisory Role, Member of Scientific Advisory Board: Hope for Stomach Cancer; Non-Financial Interests, Other, Member of Gastric and Esophageal NCCN Guideline Committees: NCCN. J. Weiss: Financial Interests, Advisory Board: Genmab, AstraZeneca, EMD Serono, Genentech, Inivata, Celgene, G1 Therapeutics, Jounce Therapeutics, AbbVie, Rakuten Medical, Nanobiotix, Azitra, Lilly, Blueprint Medicines, Pfizer, Jazz Pharmaceuticals, Boehringer Ingelheim, Regeneron; Financial Interests, Stocks/Shares: Nektar, Vessalon. M. Pelster: Financial Interests, Institutional, Principal Investigator: Arcus Biosciences, Astellas, Codiak Biosciences, CytomX, Gritstone Oncology, HiberCell, Immune-Onc Therapeutics, Surface Oncology, SQZ Biotechnologies, ZielBio; Financial Interests, Institutional, Advisory Role: Bayer, Novartis, AstraZeneca. A. Spira: Financial Interests, Personal, Other, Consulting or Advisory Role: Incyte, Mirati Therapeutics, Gritstone Oncology, Jazz Pharmaceuticals, Janssen Research & Development, Mersana, Gritstone Bio, Daiichi Sankyo/AstraZeneca, Array Biopharma, Blueprint Medicines; Financial Interests, Personal, Other, Consulting or Advisory Role / Honoraria: Amgen, Novartis, Takeda, AstraZeneca/MedImmune, Merck, Bristol-Myers Squibb; Financial Interests, Personal, Other, Honoraria: CytomX Therapeutics, Janssen Oncology, Bayer; Financial Interests, Institutional, Officer, CEO: NEXT Oncology Virginia; Financial Interests, Personal, Stocks/Shares: Eli Lilly; Financial Interests, Institutional, Invited Speaker: LAM Therapeutics, Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Newlink Genetics, Incyte, AbbVie, Ignyta, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol-Myers Squibb, Loxo, Arch Therapeutics, Gritstone, Plexxikon, Amgen, Daiichi Sankyo, ADCT, Janssen Oncology, Mirati Therapeutics, Rubius, Synthekine, Mersana, Blueprint Medicines. M. Barve: Financial Interests, Stocks/Shares: Texas Oncology Physician Associates; Financial Interests, Funding: Mary Crowley Cancer Research. S.I. Ou: Financial Interests, Personal, Invited Speaker: Pfizer, Roche; Financial Interests, Personal, Advisory Board: JNJ/Janssen, Elevation Oncology; Financial Interests, Personal, Stocks/Shares: Turning Point Therapeutics, Elevation Oncology; Financial Interests, Institutional, Invited Speaker: Pfizer, Mirati, JNJ/jassen, Merus. T.A. Leal: Financial Interests, Advisory Board: Daiichi Sankyo, Beyond Spring Pharmaceuticals, BMS, Merck, Takeda, Genentech, Invision First Lung, AstraZeneca, Novocure, Jazz Pharmaceuticals, EMD Serono, Boehringer Ingelheim, Blueprint Medicines. T. Bekaii-Saab: Financial Interests, Advisory Board: Replimune Artiva, Imugene, Immuneering, Xilis, Sun Biopharma; Financial Interests, Research Grant: BMS, Agios, Arys, Arcus, Atreca, Boston Biomedical, Bayer, Eisai, Celgene, Lilly, Clovis, Seattle Genetics, Genentech, Novartis, Mirati, Merus, Abgenomics, Incyte, Pfizer; Financial Interests, Other, Data monitoring committees: Fibrogen, Suzhou Kintor, AstraZeneca, Exelixis, Merck/Eisai, PanCan, 1Globe; Financial Interests, Other, Inventions/patents: WO/2018/183488: human PD-1peptide vaccines and uses thereof –Licensed to Imugene, WO/2019/055687: methods and compositions for the treatment of cancer cachexia –Licensed to Recursion; Financial Interests, Advisory Role: Ipsen, Arcus, Pfizer, Seattle Genetics, Bayer, Genentech, Incyte, Eisai, Merck, Stemline, AbbVie, Boehringer Ingelheim, Janssen, Daichii Sankyo, Natera, TreosBio, Celularity, Exact Science, Sobi, Beigene, Kanaph, AstraZeneca, Deciphera, MJH Life Sciences, Aptitude Health, Illumina, Foundation Medicine. J.G. Christensen: Financial Interests, Advisory Board: Bridge Biosciences; Financial Interests, Officer: Mirati Therapeutics; Financial Interests, Full or part-time Employment: Mirati Therapeutics; Financial Interests, Stocks/Shares: Mirati Therapeutics. T. Kheoh: Financial Interests, Full or part-time Employment: Mirati Therapeutics; Financial Interests, Stocks/Shares: Mirati Therapeutics. K. Velastegui: Financial Interests, Full or part-time Employment: Mirati Therapeutics. H. Der Torossian: Financial Interests, Full or part-time Employment: Mirati Therapeutics; Financial Interests, Stocks/Shares: Mirati Therapeutics. R. Yaeger: Financial Interests, Advisory Board: Array Biopharma/ Pfizer, Mirati Therapeutics, Natera; Financial Interests, Research Grant: Array Biopharma/ Pfizer, Boehringer Ingelheim, Mirati Therapeutics.
315O - Sotorasib in combination with panitumumab in refractory KRAS G12C-mutated colorectal cancer: Safety and efficacy for phase Ib full expansion cohort
- Yasutoshi Kuboki (Kashiwa, Japan)
Abstract
Background
Sotorasib (Soto), a KRASG12C inhibitor, showed modest clinical activity as monotherapy in heavily pretreated patients (pts) with
Methods
CodeBreaK 101 (NCT04185883) subprotocol H includes dose exploration and expansion in multiple cohorts. Key eligibility criteria for the refractory mCRC cohort included progression on or after prior fluoropyrimidine, oxaliplatin, irinotecan and an anti-angiogenic agent. Primary endpoint is safety. Secondary endpoints include antitumor activity, progression-free survival (PFS), overall survival (OS), and pharmacokinetics (PK).
Results
As of March 25, 2022, 40 pts (75% female, median age 57.5 years) were enrolled and received oral Soto 960 mg daily and Pmab 6 mg/kg IV every 2 weeks. Median prior lines of therapy was 2. Treatment-related adverse events (TRAEs) of any grade occurred in 37 (92.5%) pts. Grade 3 TRAEs occurred in 9 (22.5%) pts; related to Soto and Pmab in 6 (15%) and 8 (20%) pts, respectively. No TRAEs were Grade >3 or resulted in treatment discontinuation. Safety findings were consistent with known profiles of Soto and Pmab. Confirmed ORR was 30% (95% CI: 16.6, 46.5). Disease control rate was 90% (95% CI: 76.3, 97.2). Tumor shrinkage of any magnitude was observed in 35 (87.5%) pts. Soto PK exposures were consistent to those observed in monotherapy studies.
Conclusions
This dataset provides further evidence of safety and tolerability for the combination of Soto and Pmab in heavily pretreated pts with
Clinical trial identification
NCT04185883.
Editorial acknowledgement
Medical writing support was provided by Tim Harrison, PharmD (Amgen Inc.).
Legal entity responsible for the study
Amgen Inc.
Funding
Amgen Inc.
Disclosure
Y. Kuboki: Financial Interests, Institutional, Writing Engagements: Amgen; Financial Interests, Institutional, Research Grant: Taiho, Astellas, Lilly, Takeda, Daiichi Sankyo, AstraZeneca, Boehringer Ingelheim, Chugai, Genmab, GlaxoSmithKline, Incyte, AbbVie; Financial Interests, Personal, Other, Consulting fees: Taiho, Takeda, Boehringer Ingelheim, Amgen; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Taiho, Ono, Lilly, Bristol-Myers Squibb. R. Yaeger: Financial Interests, Personal, Advisory Role: Natera, Array BioPharma/Pfizer, Mirati Therapeutics; Financial Interests, Institutional, Research Grant: Array BioPharma/Pfizer, Boehringer Ingelheim, Mirati Therapeutics. M.G. Fakih: Financial Interests, Institutional, Research Grant: Genentech, Verastem; Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Bayer Corporation, HalioDX, Incyte Corporation, Mirati, Pfizer, Inc., PsiOxus, Taiho Oncology, Zhuhai Yufan Biotech; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Amgen, Inc., Guardant360; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: Amgen, Inc., Bayer Corporation, GlaxoSmithKline, Nouscom, Roche/Genentech, Seattle Genetics; Financial Interests, Institutional, Other, Study-related drugs supplied to my institution: Bristol Myers Squibb. J.H. Strickler: Financial Interests, Personal, Advisory Board: SeaGen, AstraZenca, Amgen, Pfizer, Bayer, AbbVie, Natera, Viatris, Inivata, Silverback Therapeutics; Financial Interests, Personal, Other, Consulting: Mereo, GSK, Pionyr Immunotherapeutics; Financial Interests, Institutional, Invited Speaker: SeaGen, Roche Genentech, AbbVie, AstraZeneca, Amgen, AStar D3, Sanofi, Curegenix, Nektar, Leap Therapeutics, Daiichi Sankyo, Erasca, Gossamer Bio, Silverback Therapeutics. T. Masuishi: Financial Interests, Institutional, Research Grant: MSD, Daiichi Sankyo, Ono, Novartis, Amgen, Syneos Health Clinical, Boehringer Ingelheim, Pfizer, Cimic Shift Zero, Eli Lilly; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Takeda, Chugai, Merck BioPharma, Taiho, Bayer, Lilly Japan, Yakult Honsha, Sanofi, Daiichi Sankyo, Ono, Bristol-Myers Squibb. E.J. Kim: Financial Interests, Institutional, Research Grant: NGM, Erytech, Fibrogen, Eureka, Merck, BMS, Astellas, Boston Biomedical, AZ, Celgene, Halozyme, Samumed, Epicentrx; Financial Interests, Personal, Other, Consulting fees: Eisai, Taiho, Celgene, Lilly; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: Lilly. C.M. Bestvina: Financial Interests, Institutional, Research Grant: AstraZeneca, BMS; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, CVS, Genentech, Jazz, JNJ, Novartis, Pfizer, Regeneron/Sanofi, Seattle Genetics, Takeda; Financial Interests, Personal, Other, Speakers Fee: Merck; Financial Interests, Personal, Other, Support for attending meetings and/or travel: EMD Serono. C.J. Langer: Financial Interests, Personal, Advisory Role: Abbott Biotherapeutics, ARIAD, AstraZeneca, Bayer/Onyx, Bristol-Myers Squibb, Cancer Support Community, Celgene, Clarient, Clovis Oncology, Genentech/Roche, Gilead Sciences, Lilly/ImClone, Merck, Novocure, Pfizer, Takeda; Financial Interests, Institutional, Research Grant: Advantagene, ARIAD, Celgene, Clovis Oncology, Genentech/Roche, GlaxoSmithKline, Inovio Pharmaceuticals, Lilly, Merck, Stem CentRx, Trizell; Other: Amgen, Lilly, Peregrine Pharmaceuticals, Synta; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol-Myers Squibb, Genentech/Roche, Lilly/ImClone, Merck, Takeda Science Foundation. J.C. Krauss: Financial Interests, Institutional, Invited Speaker, Site PI for clinical trial: Sumitomo Dainippon Pharma Oncology, Inc., Novartis Pharmaceuticals Corporation, Amgen, Inc., Merck Sharp & Dohme Res. Labs TO Nsabp Foundation; Financial Interests, Institutional, Invited Speaker, Site PI for clinical Trial: Hutchison Medipharma Limited TO Syneos Health, LLC, Ignyta, Inc. TO Quintiles, Inc; Financial Interests, Institutional, Invited Speaker, Site PI for Clinical Trial: Isofol Medical AB; Financial Interests, Institutional, Invited Speaker, Site PI for a clinical trial: AbbVie, Inc., Bristol-Myers Squibb, MedImmune, Pfizer, Daiichi Sankyo Company, Ltd TO Syneos Health, LLC. S. Puri: Financial Interests, Personal, Other, Consulting fees: AstraZeneca, G1 Therapeutics. P. Cardona: Financial Interests, Personal, Stocks/Shares: Amgen; Financial Interests, Personal, Full or part-time Employment: Amgen. E. Chan: Financial Interests, Personal, Stocks/Shares: Amgen; Financial Interests, Personal, Full or part-time Employment: Amgen. Q. Tran: Financial Interests, Personal, Stocks/Shares: Amgen; Financial Interests, Personal, Full or part-time Employment: Amgen. D.S. Hong: Financial Interests, Personal, Other, Consultancy role: Amgen; Financial Interests, Institutional, Research Grant: Amgen, AbbVie, Adaptimmune, Adlai-Nortye, AstraZeneca, Bayer, Daiichi Sankyo, Deciphera, Eisai, Endeavor, Erasca, F. Hoffmann-La Roche, Fate Therapeutics, Genentech, Genmab, Ignyta, Infinity, Kite, Kyowa Kirin, Lilly, LOXO, Merck, Medimmune, Mirati, Mologen, Navier, NCI-CTEP, Novartis, Numab, Pfizer, Pyramid Bio, SeaGen, Takeda, TCR2, Teckro, Turning Point Therapeutics, VM Oncology, Bristol-Myers Squibb; Financial Interests, Personal, Other, Consulting: Adaptimmune, Alpha Insights, Acuta, Alkermes, Aumbiosciences, Axiom, Baxter, Bayer, Boxer Capital, BridgeBio, COR2ed, COG, Cowen, Ecor1, Gennao Bio, Genentech, Gilead, GLG, Group H, Guidepoint, HCW Precision, Immunogen, Infinity, Janssen, Liberium, MedaCorp, Medscape, Numab, Oncologia Brasil, Pfizer, Pharma Intelligence, POET Congress, Prime Oncology, RAIN, Seattle Genetics, ST Cube, Takeda, Tavistock, Trieza Therapeutics, Turning Point, WebMD, YingLing Pharma, Ziopharm; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Bayer, Genmab, AACR, ASCO, SITC, Telperian; Financial Interests, Personal, Advisory Role: Molecular Match; Financial Interests, Personal, Other, Founder Advisor: OncoResponse, Telperian.
Invited Discussant LBA24 and 315O
- Maria Elena Elez Fernandez (Barcelona, Spain)
Q&A
- All Speakers (Lugano, Switzerland)
LBA25 - FRESCO-2: A global phase III multiregional clinical trial (MRCT) evaluating the efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer
- N. Arvind Dasari (Houston, United States of America)
Abstract
Background
Effective treatment options are limited for patients (pts) with refractory metastatic colorectal cancer (mCRC). Fruquintinib (F), a highly selective, potent, oral tyrosine kinase inhibitor of VEGFR-1, -2, and -3, was approved in China in the 3L+ mCRC setting based on results from the FRESCO trial (NCT02314819). FRESCO-2 (NCT04322539) evaluated F in more heavily pre-treated pts reflecting current global practices.
Methods
FRESCO-2 was a randomized, double-blind, placebo (P)-controlled, phase 3 MRCT conducted in the US, Europe, Japan & Australia, comparing F + best supportive care (BSC) with P + BSC. F or P was given 5 mg PO, QD, 3 wks on, 1 wk off, in 28-d cycles. Key criteria: Prior chemotherapy, anti-VEGF therapy, and, if
Results
From 2Sep2020 to 14Dec2021, 691 pts were randomized; F:461 vs P:230. Baseline characteristics were balanced. F significantly improved OS (median: 7.4 m vs 4.8 m P; HR=0.66; [95% CI: 0.55, 0.80]; p<0.001) & PFS (median: 3.7 m vs 1.8 m P; HR=0.32; [95% CI: 0.27, 0.39]; p<0.001). The median duration of follow-up was 11.3 m F vs 11.2 m P. Subsequent anti-cancer therapies were 29.4% F vs 34.3% P. DCR was 55.5% F vs 16.1% P & ORR was 1.5% F vs 0% P. Grade ≥3 adverse events were 62.7% F vs 50.4% P; those occurring in ≥5% on F were hypertension (13.6% vs 0.9% P), asthenia (7.7% vs 3.9% P) & hand-foot syndrome (6.4% vs 0% P).
Conclusions
F had a significant and clinically meaningful improvement in OS in pts with refractory mCRC. F was well tolerated, with a safety profile consistent with the established profile for F monotherapy. FRESCO-2 results are consistent with FRESCO and should support a new treatment option in refractory mCRC.
Clinical trial identification
NCT04322539.
Editorial acknowledgement
Editorial support in the preparation of this abstract was provided by Team 9 Science, a Vaniam Group agency, funded by HUTCHMED International.
Legal entity responsible for the study
Hutchison Medipharma Limited.
Funding
Hutchison Medipharma Limited.
Disclosure
N.A. Dasari: Financial Interests, Institutional, Research Grant: Hutchmed, Guardant Health, Natera Inc, Eisai, Crinetics, AAA / Novartis; Financial Interests, Personal, Advisory Board: Hutchmed, Crinetics, Voluntis, AAA / Novartis, Personalis Inc. S. Lonardi: Financial Interests, Personal, Advisory Board: Amgen, merck serono, lilly, Servier, AstraZeneca, MSD, Incyte, Daiichi-Sankyo, Bristol-Myers Squibb, Mirati; Financial Interests, Personal, Invited Speaker: Pierre-Fabre, GlaxoSmithKline, Roche; Financial Interests, Institutional, Invited Speaker: Amgen, Merck Serono, Bayer, Roche, Lilly, AstraZeneca, Bristol -Myers Squibb. R. Garcia-Carbonero: Financial Interests, Personal, Advisory Board: AAA, Advanz Pharma, Amgen, Bayer, BMS, HMP, Ipsen, Merck, Midatech, MSD, Novartis, Pharma Mar, Pierre Fabre, Servier; Financial Interests, Institutional, Research Grant: BMS, MSD, Pfizer; Non-Financial Interests, Leadership Role, Global PI of investigator-initiated clinical trials (AXINET, NICENEC, PEMBROLA): BMS, MSD, Pfizer; Other, Honoraria received by spouse for advisory board or invited speaker roles: Abbie, AstraZeneca, Bayer, Boehringer, BMS, Genomica, Lilly, MSD, Merck, Novartis, Pfizer, PharmaMar, Roche, Sanofi, Servier, Takeda. M.E. Elez Fernandez: Financial Interests, Personal, Advisory Board: Hoffman La - Roche, Servier, Amgen, Merck Serono, Sanofi, Bayer, Pierre Fabre, MSD; Financial Interests, Personal, Invited Speaker: Organon, Novartis; Financial Interests, Institutional, Funding: Hoffmann-La Roche Ltd, Sanofi Aventis Recherche & Développement, Amgen Inc., Boehringer Ingelheim, Novartis Farmacéutica SA, Bristol-Myers Squibb International Corporation, BeiGene, HalioDX SAS, Janssen-Cilag SA, Merck Health KGAA, Merck Sharp & Dohme de España SA, PharmaMar SA, Servier, Taiho Pharma USA Inc, Hutchison MediPharma International, Menarini, Merus NV, Pfizer, Mirati, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, Celgene International SARL, Debiopharm International SA, Genentech Inc, MedImmune; Non-Financial Interests, Other, Coordinator of the SEOM +MIR Section of Residents and Young Assistants: Sociedad Española de Oncología Médica (SEOM); Non-Financial Interests, Other, Speaker of the ESMO Academy: European Society for Medical Oncology (ESMO); Non-Financial Interests, Other, Volunteer member of the ASCO Annual Meeting Scientific Program Committee: Developmental Therapeutics – Immunotherapy: American Society of Clinical Oncology (ASCO); Other, Travel, accommodations, expenses: Roche, Merck Serono, Sanofi, Amgen, Array BioPharma, Servier, Bristol Myers Squibb. T. Yoshino: Financial Interests, Personal, Invited Speaker: Chugai, Merck Biopharma, Bayer, Ono, MSD; Financial Interests, Institutional, Invited Speaker: Ono, Sanofi, Daiichi Sankyo, Chugai, Pfizer; Financial Interests, Institutional, Research Grant: Taiho, MSD, Ono, Amgen, Genomedia, Sysmex, Daiichi Sankyo, Chugai, Boehringer Ingelheim. A.F. Sobrero: Financial Interests, Personal, Advisory Board: servier, bms, msd, incyte; Financial Interests, Personal, Invited Speaker: Bayer, Pierre Fabre, Merck, Amgen, Sanofi; Financial Interests, Personal, Stocks/Shares: Bayer. J.C. Yao: Financial Interests, Personal, Advisory Board: Ipsen, Chiasma Pharma, Amgen, Critics; Financial Interests, Personal, Other, Consultancy: Hutchison Medi Pharma; Financial Interests, Personal, Invited Speaker: Medscape; Financial Interests, Institutional, Invited Speaker: Advanced Accelerator Applications International, Novartis. P. García Alfonso: Financial Interests, Institutional, Research Grant: Roche, Lilly, Sanofi, Merck, Amgen, Servier, Pierre Fabre; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche, Lily, Sanofi, Merck, Amgen, Servier, Pierre Fabre; Financial Interests, Personal, Sponsor/Funding, Travel: Roche, Lily, Sanofi, Merck, Amgen, Servier, Pierre Fabre; Financial Interests, Personal, Advisory Board: Roche, Lily, Sanofi, Merck, Amgen, Servier, Pierre Fabre. A. Sartore Bianchi: Financial Interests, Personal, Other, Consulting Fees: Amgen, Bayer, Novartis, Servier; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Amgen, Bayer; Financial Interests, Personal, Advisory Board: Amgen, Bayer, Novartis, Servier. J. Tomasek: Financial Interests, Personal, Other, Consulting: Servier, Bristol Myers Squibb, Amgen, Pierre Fabre, Merck; Financial Interests, Personal, Invited Speaker: Servier, Bristol Myers Squibb, Amgen, Pierre Fabre, Merck; Financial Interests, Personal, Other, Travel: Merck, Novartis. G. Chong: Other, Personal and Institutional, Funding, Research Funding: HutchMed International Corp., Isofol, BMS, Regeneron, Pharmacyclics, Bayer, Merck Serono, AstraZeneca, Incyte; Other, Personal, Other, Consulting Fees: BMS. Z. Yang: Financial Interests, Personal, Full or part-time Employment: HUTCHMED International Corporation. W. Schelman: Financial Interests, Personal, Stocks/Shares: HutchMed International Corp.; Financial Interests, Personal, Full or part-time Employment: HutchMed International Corp.. M. Kania: Financial Interests, Personal, Full or part-time Employment: Hutchison MediPharma International Inc., ; Financial Interests, Personal, Stocks/Shares: Hutchison MediPharma International Inc., . J. Tabernero: Financial Interests, Personal, Advisory Board, scientific consultancy role: Orion Biotechnology, Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daichii Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc., HalioDX SAS, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics, TheraMyc, Hutchinson MediPharma International, Scandion Oncology, Ona Therapeutics, Sotio Biotech, Inspirna Inc, Scorpion Therapeutics; Financial Interests, Personal, Invited Speaker, educational collaboration: Medscape Education, Physicians Education Resource (PER), PeerView Institute for Medical Education, Imedex; Financial Interests, Personal, Invited Speaker, educacional collaboration: MJH Life Sciences; Financial Interests, Personal, Other, Stocks: Oniria Therapeuics; Financial Interests, Institutional, Research Grant, ACRCelerate: Colorectal Cancer Stratified: Fundación Científica de la Asociación Española Contra el Cáncer; Financial Interests, Institutional, Research Grant, OPTIMISTICC: Opportunity to Investigate the Microbiome’s Impact on Science and Treatment In Colorectal Cancer: Cancer Research UK; Financial Interests, Institutional, Funding, Clinical Trials & Research: Amgen Inc, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc, Janssen-Cilag International NV, Merck Health KGAA, Merck, Sharp & Dohme de España, SA, Novartis Farmacéutica SA, PharmaMar SA, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA, Inc, BeiGene, Boehringer Ingelheim, HalioDX SAS, Hutchinson Medipharma, MedImmune, Menarini, Merus N V, Pfizer, Mirati; Non-Financial Interests, Invited Speaker, Board of Directors: Cancer Core Europe, Spanish Association Against Cancer -AECC; Non-Financial Interests, Invited Speaker, General Assembly: Horizon Europe Cancer Mission; Non-Financial Interests, Leadership Role, External Scientific Committee: Institute for Health Research INCLIVA – Clinical Hospital of Valencia, IdiSNA –Universidad de Navarra; Non-Financial Interests, Leadership Role, Scientific Advisory Board: Spanish National Cancer Research Centre (CNIO); Non-Financial Interests, Advisory Role, International Scientific Evaluation Committee: Bosch Health Campus (BHC); Non-Financial Interests, Advisory Role, Review Board: National Decade Against Cancer (NCT) - German Consortium for Translational Cancer Research (DKTK); Non-Financial Interests, Advisory Role, Scientific Advisory Board: Karolinska Comprehensive Cancer Centre; Non-Financial Interests, Advisory Role, International Review Committee (IRC): Oncode Institute; Non-Financial Interests, Advisory Role, Scientific Advisory Board (SAB): Oslo University Hospital Comprehensive Cancer Centre (OUH CCC); Non-Financial Interests, Leadership Role, Governance Advisory Committee: European Organization for Research and Treatment of Cancer -EORTC; Non-Financial Interests, Leadership Role, Vice Chairman: World Innovative Networking (WIN) Consortium in Personalized Cancer Medicine; Non-Financial Interests, Other, Coordinating PI & Steering Committee Member. Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutical LP, Boehringer Ingelheim, MedImmune, Menarini, Merck Healthcare KGAA, Merck, Sharp & Dohme de España SA, Pfizer, Servier; Non-Financial Interests, Principal Investigator, Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutics LP, BeiGene, Boehringer Ingelheim, Debiopharm International SA, Bristol-Myers Squibb International Corporation, Celgene International SARL, F. Hoffmann-La Roche Ltd, Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, MedImmune, Menarini, Merck Healthcare KGAA, Merck, Sharp & Dohme de España SA, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc; Non-Financial Interests, Other, Steering Committee Member. Clinical Trials & Research: Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, Merus NV, Taiho Pharma USA Inc; Non-Financial Interests, Other, Coordinating PI. Clinical Trials & Research: Mirati; Non-Financial Interests, Member: AACR, ASCO, EACR, EORTC, SEOM; Other, President: Oncology Master Plan – Catalonia Department of Health; Other, Other, Advisory Committee: Advisory Committee on Pharmaceutical Provision Financing under the Spanish National Health System. C. Eng: Financial Interests, Institutional, Research Grant, To Vanderbilt Ingram Cancer Center: Pfizer, Elevar, Merck, Gritstone; Financial Interests, Personal, Other, Consulting: Bayer, GSK, Halio Dx, Boston Scientific. All other authors have declared no conflicts of interest.
316O - Genomic mechanisms of acquired resistance of patients (pts) with BRAF V600E-mutant (mt) metastatic colorectal cancer (mCRC) treated in the BEACON study
- Scott Kopetz (Houston, United States of America)
Abstract
Background
In the randomized phase III BEACON study (NCT02928224), encorafenib + cetuximab ± binimetinib regimens improved overall survival and objective response rate vs standard of care (control) in pts with previously treated
Methods
Plasma samples were collected at baseline and end of treatment (EOT) and were analyzed using GuardantOMNI to evaluate somatic alterations, including nonsynonymous mutations, amplification (focal/amplified), and rearrangements. Genomic changes were evaluated at individual pt level to characterize acquired alterations.
Results
To explore mechanisms of resistance, paired baseline and EOT samples were evaluated from 320/665 (48.1%) pts in this analysis.
Conclusions
ctDNA analyses revealed that MAPK pathway reactivation is a common mechanism of resistance for
Clinical trial identification
NCT02928224.
Editorial acknowledgement
Medical writing support was provided by Alexus Kolb, PhD, from Caudex and was funded by Pfizer.
Legal entity responsible for the study
BEACON CRC was sponsored by Pfizer in collaboration with Merck KGaA, ONO Pharmaceutical, and Pierre Fabre.
Funding
Pfizer in collaboration with Merck KGaA, ONO Pharmaceutical, and Pierre Fabre.
Disclosure
S. Kopetz: Financial Interests, Personal, Advisory Board: Roche, EMD Serono, Merck, Novartis, Lilly, Boehringer Ingelheim, Boston Biomedical, AstraZeneca, Bayer, Pierre Fabre, Redx Pharma, Ipsen, Daiichi, Natera, HalioDx, Jacobio, Pfizer, Repare Therapeutics, GlaxoSmithKline, Jazz, Xilis, Abbvie, Gilead, Mirati, Flame, Servier, Carina, Bicara, Endeavor BioMedicines, Numab Pharma, Janssen; Financial Interests, Personal, Other, Research: Inivata; Financial Interests, Personal, Stocks/Shares: Lutris, Iylon, Navire, Xilis. D.A. Murphy: Financial Interests, Personal, Stocks/Shares: Pfizer; Financial Interests, Personal, Full or part-time Employment: Pfizer. J. Pu: Non-Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer. R. Yaeger: Financial Interests, Personal, Advisory Role: Array BioPharma, Mirati, Natera; Financial Interests, Institutional, Funding, Research Funding: Array BioPharma, Boehringer Ingelheim, Mirati, Pfizer. F. Ciardiello: Financial Interests, Personal, Advisory Board: Roche, Merck Serono, Servier, Pierre Fabre, Pfizer; Financial Interests, Institutional, Research Grant: Merck Serono, Roche, Amgen; Financial Interests, Institutional, Invited Speaker: Pfizer, Pierre Fabre, Servier. J. Desai: Financial Interests, Personal, Advisory Role: Amgen, Bayer, BeiGene, Eisai, GlaxoSmithKline, Pierre Fabre; Financial Interests, Institutional, Funding, Research Funding: AstraZeneca/MedImmune, BeiGene, Bionomics, Bristol Myers Squibb, GlaxoSmithKline, Lilly, Novartis, Roche. E. Van Cutsem: Financial Interests, Personal, Advisory Board, Advisory board and/or Speaking: AbbVie, Array, Astellas, AstraZeneca, Bayer, Beigene, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Daiichi, Halozyme, GSK, Helsinn, Incyte, Ipsen, Janssen Research, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Pierre Fabr; Financial Interests, Institutional, Funding, research grant paid to institution: Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier. H.S. Wasan: Financial Interests, Personal, Advisory Board, Advisory Boards and Invited Speaker: Incyte, Pierre Fabre, Servier, Bayer, Roche/Genentech/ FM AG, SIRTEX medical ERYTECH, Celgene, Array BioPharma, Merck KGaA: BMS; Financial Interests, Personal, Invited Speaker, Trial steering committee and advisory: Zymeworks; Financial Interests, Personal and Institutional, Invited Speaker, Trial PI steering committee and advisory: Sirtex Medical; Financial Interests, Personal, Other, Consultancy for Submission for UK approval (BSI): ONCOSL; Non-Financial Interests, Advisory Role, Trial steering committee: Pfizer; Non-Financial Interests, Advisory Role, UK NICE submission: Bayer, Pierre Fabre. T. Yoshino: Financial Interests, Personal, Invited Speaker: Chugai, Merck Biopharma, Bayer, Ono, MSD; Financial Interests, Institutional, Invited Speaker: Ono, Sanofi, Daiichi Sankyo, Chugai, Pfizer; Financial Interests, Institutional, Research Grant: Taiho, MSD, Ono, Amgen, Genomedia, Sysmex, Daiichi Sankyo, Chugai, Boehringer Ingelheim. B. Alkuzweny: Financial Interests, Personal, Full or part-time Employment: Pfizer. T. Xie: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer. X. Zhang: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer; Financial Interests, Personal, Royalties: Johns Hopkins University. J. Tabernero: Financial Interests, Personal, Advisory Board, scientific consultancy role: Orion Biotechnology, Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daichii Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc., HalioDX SAS, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics, TheraMyc, Ona Therapeutics, Hutchinson MediPharma International, Avvinity, Scandion Oncology, Sotio Biotech, Inspirna Inc; Financial Interests, Personal, Invited Speaker, educational collaboration: Medscape Education, Physicians Education Resource (PER), PeerView Institute for Medical Education, Imedex; Financial Interests, Personal, Invited Speaker, educacional collaboration: MJH Life Sciences; Financial Interests, Institutional, Research Grant, ACRCelerate: Colorectal Cancer Stratified: Fundación Científica de la Asociación Española Contra el Cáncer; Financial Interests, Institutional, Research Grant, OPTIMISTICC: Opportunity to Investigate the Microbiome’s Impact on Science and Treatment In Colorectal Cancer: Cancer Research UK; Financial Interests, Institutional, Funding, Clinical Trials & Research: Amgen Inc, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb International Corporation, Genentech Inc, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Janssen-Cilag International NV, Merck Health KGAA, Merck, Sharp & Dohme de España, SA, Novartis Farmacéutica SA, PharmaMar SA, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA, Inc, BeiGene, Boehringer Ingelheim, HalioDX SAS, Hutchinson Medipharma, Pfizer, MedImmune, Menarini, Merus N V, Mirati; Non-Financial Interests, Invited Speaker, Board of Directors: Cancer Core Europe, Spanish Association Against Cancer -AECC; Non-Financial Interests, Invited Speaker, General Assembly: Horizon Europe Cancer Mission; Non-Financial Interests, Advisory Role, Scientific Advisory Board: Karolinska Comprehensive Cancer Centre; Non-Financial Interests, Leadership Role, External Scientific Committee: Institute for Health Research INCLIVA – Clinical Hospital of Valencia, IdiSNA –Universidad de Navarra; Non-Financial Interests, Leadership Role, Scientific Advisory Board: Spanish National Cancer Research Centre (CNIO); Non-Financial Interests, Advisory Role, International Scientific Evaluation Committee: Bosch Health Campus (BHC); Non-Financial Interests, Advisory Role, Review Board: National Decade Against Cancer (NCT) - German Consortium for Translational Cancer Research (DKTK); Non-Financial Interests, Advisory Role, International Review Committee (IRC): Oncode Institute; Non-Financial Interests, Advisory Role, Scientific Advisory Board (SAB): Oslo University Hospital Comprehensive Cancer Centre (OUH CCC); Non-Financial Interests, Leadership Role, Governance Advisory Committee: European Organization for Research and Treatment of Cancer -EORTC; Non-Financial Interests, Principal Investigator, Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutics LP, BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, MedImmune, Menarini, Merck Healthcare KGAA, Merck, Sharp & Dohme de España SA, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc; Non-Financial Interests, Leadership Role, Vice Chairman: World Innovative Networking (WIN) Consortium in Personalized Cancer Medicine; Non-Financial Interests, Other, Coordinating PI & Steering Committee Member. Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutical LP, Boehringer Ingelheim, MedImmune, Menarini, Merck Healthcare KGAA, Merck, Sharp & Dohme de España SA, Pfizer, Servier; Non-Financial Interests, Other, Steering Committee Member. Clinical Trials & Research: Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc., Hutchinson Medipharma, HalioDX SAS, Janssen-Cilag International NV, Merus NV, Taiho Pharma USA Inc; Non-Financial Interests, Other, Coordinating PI. Clinical Trials & Research: Mirati; Non-Financial Interests, Member: AACR, ASCO, EACR, EORTC, SEOM; Other, Other, President: Oncology Master Plan – Catalonia Department of Health; Other, Other, Advisory Committee: Advisory Committee on Pharmaceutical Provision Financing under the Spanish National Health System.
Invited Discussant LBA25 and 316O
- Filippo Pietrantonio (Milan, Italy)
Q&A
- All Speakers (Lugano, Switzerland)