LBA27 - Additional analyses of MOUNTAINEER: A phase II study of tucatinib and trastuzumab for HER2-positive mCRC

Background

HER2 amplification/overexpression (HER2+) occurs in ∼3-5% of patients (pts) with metastatic colorectal cancer (mCRC). The primary analysis of MOUNTAINEER (NCT03043313) in cohorts A+B treated with tucatinib (TUC) + trastuzumab (Tras) was previously reported and showed tolerability and a confirmed objective response rate (cORR) per blinded independent central review (BICR) of 38.1%. Here, additional results of TUC monotherapy (cohort C) are reported.

Methods

have been reported in a prior presentation (Strickler et al. ESMO-WCGI 2022 abstract no. LBA-2). Eligible pts had HER2+ (per local IHC, ISH, or NGS testing) RAS WT mCRC refractory to standard of care. Pts who initially received TUC monotherapy could cross over and receive TUC + Tras for radiographic progression or stable disease by 12 weeks. Prespecified analyses for cohort C include ORR by 12 weeks and disease control rate (DCR) by BICR; cORR by BICR for crossover pts, and safety for monotherapy and crossover pts.

Results

As of 28 Mar 2022, 86 pts received ≥1 dose of study treatment in cohorts A+B and 30 pts in cohort C. The ORR by week 12 in cohort C was 3.3% (95% CI, 0.1, 17.2) with DCR of 80.0%. Twenty-eight of 30 pts (93.0%) crossed over to received TUC + Tras, with cORR of 17.9% (95% CI, 6.1, 36.9). The most common AEs with TUC monotherapy were diarrhoea (33.3%), abdominal pain (20.0%), and fatigue (20.0%), which were grade (gr) 1 or 2; the most common gr ≥3 events were ALT/AST increase (6.7% for both). The most common AE for post-crossover pts was diarrhoea (35.7%) which was gr 1 or 2; the most common gr ≥3 events were ALT/AST increase (7.1% and 10.7%, respectively). There were no fatal AEs with TUC monotherapy or TUC + Tras.

Conclusions

TUC monotherapy and TUC + Tras after crossover were well tolerated, consistent with the primary analysis. Disease stabilization was observed in most pts on TUC monotherapy; radiographic responses increased slightly after Tras addition. Monotherapy, crossover, and response data from the primary analysis show that concurrent initiation of dual HER2 blockade with TUC + Tras achieves optimal clinical benefit.

Clinical trial identification

NCT03043313.

Editorial acknowledgement

Under guidance of the authors, assistance in medical writing was provided by Irene Park, PhD, of Seagen Inc. and was funded by Seagen Inc. in accordance with Good Publication Practice (GPP3) guidelines.

Legal entity responsible for the study

Seagen Inc.

Funding

This study was sponsored by Seagen Inc., Bothell WA, USA. in collaboration with Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.

Disclosure

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. A. Cercek: Financial Interests, Personal, Other, Consulting: Array Biopharma, Bayer, Proteus; Financial Interests, Institutional, Research Grant: AbbVie, Rgenix, Seagen Inc., Tesaro. S. Siena: Financial Interests, Personal, Other, Consulting: Amgen, Bayer, Bristol-Myers Squibb, CheckmAb, Clovis Oncology, Daiichi Sankyo, Incyte, Merck, Novartis, Seagen Inc., Roche/Genentech; Financial Interests, Personal, Ownership Interest, Equity ownership: Guardant, Myriad; Financial Interests, Personal, Royalties: Amgen; Financial Interests, Institutional, Research Grant: MSD Oncology; Financial Interests, Personal, Other, Travel expenses: Amgen, Bayer, Roche. T. André: Financial Interests, Personal, Advisory Board, Advosiry Board on February 12, 2021: Astellas pharma; Financial Interests, Personal, Advisory Board, Advisory Board on February 2021: Kaleido Biosciences; Financial Interests, Personal, Invited Speaker, and advisory board: Amgen; Financial Interests, Personal, Invited Speaker, Ivited speaker in a symposuim december 2020: AstraZeneca; Financial Interests, Personal, Advisory Board, and consultant fees and consultant contract: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board, Advisory board in January 2020: Clovis; Financial Interests, Personal, Advisory Board, Advisory board in january 2020: Gritstone Oncology; Financial Interests, Personal, Advisory Board: Haliodx; Financial Interests, Personal, Advisory Board, and consultant fees/consultant contract and invited speaker: MSD Oncology; Financial Interests, Personal, Invited Speaker, and other: Pierre Fabre; Financial Interests, Personal, Invited Speaker, in an symposuim in 2020: Roche; Financial Interests, Personal, Invited Speaker, in a meeting in 2019: Ventana; Financial Interests, Personal, Invited Speaker, In a educational meeting in 2019: Sanofi; Financial Interests, Personal, Advisory Board, in a symposuim in 2020: Servier; Financial Interests, Personal, Expert Testimony, Consultant with personnal fees and invited speaker: Servier; Financial Interests, Personal, Advisory Board, in 2019: GSK; Financial Interests, Personal, Invited Speaker, in 2020 and 2021: GSK; Financial Interests, Personal, Expert Testimony, consultant contract: Seagen; Financial Interests, Personal, Invited Speaker, Virtual symposuimLecture: 1 MSI-H CRC: Implementation of Immunotherapy in clinical practice (30 minutes) – (this will be pre-recorded)Q&A – Live Q&A – (10 minutes) (on July 2, 2021): MSD Oncology; Financial Interests, Personal, Invited Speaker, June 2022: Sanofi; Financial Interests, Personal, Expert Testimony, Contract: Merck & Co., Inc, Gritstone Oncologie; Financial Interests, Personal, Advisory Board, Contrat: BMS; Financial Interests, Institutional, Other, Investigator and scientific comitee president: Gercor Academic group; Financial Interests, Institutional, Invited Speaker, PI Garnet study: GSK; Financial Interests, Institutional, Invited Speaker, Keynote 164 and 171 and 811: MSD; Financial Interests, Institutional, Invited Speaker, BMS CA209-8HW, BMS CA209-142, BMS CA209-577: BMS; Financial Interests, Institutional, Invited Speaker, SPOTLIGHT study: Astellas; Financial Interests, Personal, Invited Speaker, and internationnal PI: Servier; Non-Financial Interests, Invited Speaker, Vice President: Gercor group; Non-Financial Interests, Invited Speaker, Member of scientific commitee: ARCADFoundation. K. Ng: Financial Interests, Personal, Other, Consulting: Bayer, Genentech/Roche, Lilly, Seagen Inc., Tarrex Biopharma, X-Biotix Therapeutics; Financial Interests, Institutional, Research Grant: Celgene, Genentech/Roche, Gilead, Pharmavite, Revolution Medicines, Trovagene. E. Van Cutsem: Financial Interests, Personal, Advisory Board: AbbVie, Astellas, AstraZeneca, Bayer, Beigene, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Halozyme, GSK, Helsinn, Incyte, Ipsen, Janssen Research, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Pierre Fabre, Roche, Seagen Inc., Servier, Sirtex, Terumo, Taiho, TRIGR, Zymeworks; Financial Interests, Institutional, Research Grant: Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Seagen Inc., Servier. C. Wu: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Array Biopharma, Pfizer; Financial Interests, Personal, Invited Speaker: PrecisCA; Financial Interests, Institutional, Invited Speaker, PI for investigator initiated clinical trial: Vaccinex; Financial Interests, Institutional, Invited Speaker, local PI for phase 3 clinical trial: Boston Biomedical Inc; Financial Interests, Institutional, Invited Speaker: Lycera, Seagen, Symphogen, Rapt Therapeutics, INBRX; Non-Financial Interests, Advisory Role, Safety monitoring committee: Seagen. A.S. Paulson: Financial Interests, Personal, Invited Speaker, Medical education, non-branded, industry sponsored: Ideo Oncology; Financial Interests, Personal, Advisory Board: Amgen, BMS, Eisai, Ipsen, Incyte, Exelixis, AAA, Pfizer, QED, Lilly, Mirati, Hutchinson, Astellas; Financial Interests, Personal, Stocks/Shares: alexion, Actinium, Aptose; Financial Interests, Invited Speaker: Ipsen, Hutchinson, BMS, Exelixis, hutchinson med, Taiho, Lilly, AstraZeneca, Incyte, Seattle Genetics, Deciphera, Tempus, Zentalis, G1 therapeutics, Merck, Camurus, Novartis, Surface, Relay Therapeutics; Financial Interests, Institutional, Invited Speaker: Mirati, Bayer. J. Hubbard: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Institutional, Advisory Board: Incyte, Bayer, BeiGene; Financial Interests, Institutional, Invited Speaker: Boston Biomedical, Senhwa Biosciences, Bayer, Merck, Taiho Pharmaceutical, TreoBio, Hutchison MediPharma, Seattle Genetics, Tovogene, TriOncology, Incyte, Pionyr, G1 Therapeutics, eFFECTOR Therapeutics, Roche. A. Coveler: Financial Interests, Institutional, Invited Speaker: Seagen, AbGenomics, Novocure, Amgen, Actuate Therapeutics, Surface Oncology, Nucana, Nextrast. C. Fountzilas: Financial Interests, Institutional, Research Grant: Pfizer Inc, Taiho Oncology, Merck Sharp & Dohme Corp., National Comprehensive Cancer Network; Financial Interests, Institutional, Invited Speaker: Seattle Genetics, Inc., TransThera Biosciences, AstraZeneca, Aravive, Inc., Merck Sharp & Dohme Corp., Puma Biotechnology, Kadmon, Astellas Pharma, Pfizer Inc, Dragonfly Therapeutics, MedImmune, LLC., Hoosier Cancer Research Network, Incyte Corporation, Rafael Pharmaceuticals, Kinex Phamaceuticals, Syndax Pharmaceuticals, SWOG, National Cancer Institute, Erythech Pharma, Lilly, Corcept Therapeutics, Ipsen. A. Kardosh: Financial Interests, Personal, Advisory Board: Exelixus; Financial Interests, Personal, Full or part-time Employment: OHSU. P.M. Kasi: Financial Interests, Personal, Advisory Board, Consultancy/Advisory Board: Foundation Medicine, Natera Oncology, AstraZeneca, Merck MSD, Tempus, Bayer, Lilly, Delicath Systems, QED Therapeutics, Servier, Taiho Oncology, Exact Sciences, Eisai; Financial Interests, Institutional, Advisory Board, Consultancy/Advisory Board: Taiho, Ipsen; Financial Interests, Institutional, Funding, Investigator initiated trial cooperative group PI trial support and funding: Tersera; Financial Interests, Institutional, Funding, Investigator initiated trial trial support and funding: Boston Scientific. H.J. Lenz: Financial Interests, Personal, Advisory Board, Advisory Role and Lectures: Bayer; Financial Interests, Personal, Advisory Board, Advisory ROle and Lectures: Merck; Financial Interests, Personal, Advisory Board, Advisory Role and lecture: ROche; Financial Interests, Personal, Advisory Board: Jazz Pharmaceuticals, oncocyte, Orion, Astellas, BMS; Financial Interests, Personal, Advisory Board, Scientific Advisory Board: 3T Biosscience; Financial Interests, Personal, Advisory Board, Advisory Board: Fulgent. K.K. Ciombor: Financial Interests, Personal, Advisory Board: Pfizer, Merck, Lilly/Loxo, Replimune, Personalis; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Institutional, Invited Speaker: Genentech, Merck, Incyte, Seagen, BMS, Nucana, Daiichi Sankyo, Calithera, Array. M.E. Elez Fernandez: Financial Interests, Personal, Advisory Board: Hoffman La - Roche, Bristol Myers Squibb, Servier, Amgen, Merck Serono, Array Biopharma, Sanofi, Bayer; Financial Interests, Institutional, Research Grant: Hoffman La-Roche, Sanofi Aventis, Amgen, Merck Serono, MSD, Boehringer Ingelheim, AbbVie, Pierre-Fabre, Novartis, Bristol-Myers Squibb, GlaxoSmithKline, Medimmune, Array Pharmaceuticals, AstraZeneca. D.L. Bajor: Financial Interests, Personal, Other, Consulting: Avoro Capital, BridgeBio Pharma, Cardinal Health, Tempus; Financial Interests, Institutional, Research Grant: Apixigen, Bristol-Myers Squibb/Celgene, Calithera Biosciences, GlaxoSmithKline, Rafael Pharma, Seagen Inc., Tesaro. M. Stecher: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Stocks/Shares: Seagen Inc. W. Feng: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Stocks/Shares: Seagen Inc. T. 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