66O - MyPathway: A multiple target, multiple basket study of targeted treatments in tissue-agnostic cohorts of patients (pts) with advanced solid tumors

Background

Targeted agents have activity against indicated tumors, but data are limited in other tumor types with relevant alterations. MyPathway (NCT02091141) is a tissue-agnostic, non-randomized, phase IIa multiple basket trial assessing targeted agent activity for advanced solid tumors with matched alterations but no FDA indication. We previously reported objective response rates (ORR) from MyPathway in pts with HER2 amplification and/or overexpression (23.3%; pertuzumab + trastuzumab [P+H]), tumor mutational burden ≥16 mut/Mb (TMB-H; 38.1%; atezolizumab), and ALK rearrangements and alterations (30% and 0%; alectinib). Here, we describe outcomes in HER2 subgroups and in the BRAF (vemurafenib ± cobimetinib [V±C]), Hedgehog (Hh; vismodegib), and EGFR (erlotinib) arms (data cutoff 24 Mar 2022).

Methods

Alterations were identified pre-enrollment in pts aged ≥18 years using routine assays. Primary endpoint was ORR. Safety was also assessed.

Results

MyPathway enrollment was between Apr 2014 and Jul 2020 (N=672). Pts had tumors with diverse alterations (e.g. amplifications, non-synonymous mutations) in HER2 (n=357), BRAF (n=70), ALK (n=21), TMB-H (n=174), Hh (n=37), or EGFR (n=13). Among pts with traditionally defined driver alterations, HER2 positive (IHC 3+ or ICH 2+/ISH+) (ORR 37%; 10 tumor types) and BRAF V600E (48% V; 36% V+C; 17 tumor types) showed common pan-tumor driver biology with some responsiveness to matched therapy; EGFR mutations did not, but number of pts was low (8% of 13 pts) (Table). Signal seeking explorations with relevant therapy showed an ORR of 7% (4/61) in pts with HER2 mutations without amplification and 11% (4/37) in pts with Hh alterations. No new safety signals were observed.

Conclusions

Targeted therapy in a tumor-agnostic setting is active. Routine assays can identify therapies with meaningful activity for pts with limited treatment options and high unmet medical need. Table: 66O

TEAE, treatment-emergent adverse event^an=27 treated with V and n=1 with V+C

Clinical trial identification

NCT02091141.

Editorial acknowledgement

Medical writing support provided by Ashfield MedComms, an Ashfield Health Company, and funded by F. Hoffmann-La Roche/Genentech.

Legal entity responsible for the study

F. Hoffmann-La Roche/Genentech.

Funding

F. Hoffmann-La Roche/Genentech.

Disclosure

C.F. Friedman: Non-Financial Interests, Advisory Board, Compensation waived: Merck, Genentech; Financial Interests, Other, Personal fees: Arch Oncology, Bristol Myers Squibb; Non-Financial Interests, Principal Investigator: Daiichi, Bristol Myers Squibb, Genentech/Roche, Merck, AstraZeneca. C. Swanton: Financial Interests, Research Grant: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Pfizer, Roche-Ventana, Invitae (previously Archer Dx Inc - collaboration in minimal residual disease sequencing technologies), Ono Pharmaceutical; Financial Interests, Leadership Role, Chief Clinician: Cancer Research UK; Financial Interests, Principal Investigator, Chief Investigator for the MeRmaiD 1 and 2 clinical trials: AstraZeneca; Financial Interests, Principal Investigator, Chief Investigator of the NHS Galleri trial: National Health Service (NHS); Financial Interests, Advisory Role: Amgen, AstraZeneca, Pfizer, Novartis, GlaxoSmithKline, MSD, Bristol Myers Squibb, Illumina, Genentech, Roche-Ventana, GRAIL, Medicxi, Metabomed, Bicycle Therapeutics, Roche Innovation Centre Shanghai, the Sarah Cannon Research Institute; Financial Interests, Stocks/Shares: Epic Bioscience, Bicycle Therapeutics; Financial Interests, Stocks/Shares, stock and co-founder: Achilles Therapeutics. D.R. Spigel: Financial Interests, Advisory Role: Roche/Genentech, Novartis, Celgene, Bristol Myers Squibb, AstraZeneca, Pfizer, Boehringer Ingelheim, AbbVie, Foundation Medicine, GlaxoSmithKline, Lilly, Merck, Moderna Therapeutics, Nektar, Takeda, Amgen, TRM Oncology, Precision Oncology, Evelo Therapeut, Illumina, PharmaMar, G1 Therapeutics, Neon Therapeutics, Celldex, Clovis Oncology, Daiichi Sankyo, EMD Serono, Acerta Pharma, Oncogenex, Astellas Pharma, GRAIL, Transgene, Aeglea Biotherapeutics, Tesaro, Ipsen, ARMO BioSciences, Amgen, Millennium, Genzyme, Intuitive Surgical, Purdue Pharma, Spectrum Pharmaceuticals, Sysmex. R. Bose: Financial Interests, Other, Consultant: Roche/Genentech; Financial Interests, Advisory Role, Received honoraria: Roche/Genentech, Foundation Medicine, Novartis; Financial Interests, Research Grant, Research funding: Puma Biotechnology. H.A. Burris: Financial Interests, Full or part-time Employment: HCA Healthcare/Sarah Cannon; Financial Interests, Stocks/Shares: HCA Healthcare/Sarah Cannon; Financial Interests, Funding, Research funding: Bristol Myers Squibb, Incyte, AstraZeneca, MedImmune, Macrogenics, Novartis, Boehringer Ingelheim, Lilly, Seattle Genetics, Merck, Agios, Jounce Therapeutics, Moderna Therapeutics, GlaxoSmithKline, Verastem, Tesaro, BioMed Valley Disc, TG Therapeutics, Vertex, eFFECTOR Therapeutics, Janssen, BioAtla, CicloMed, Harpoon Therapeutics, Arch, Arvinas, Revolution Medicines, Array BioPharma, Bayer, Kymab, Pfizer, Takeda/Millennium, Foundation Medicine, EMD Serono, ARMO BioSciences, CALGB, Hengrui Therapeutics, XBiotech, Zymeworks, Coordination Pharmaceuticals, NGM Biopharmaceuticals, Gossamer Bio, Ryvu Therapeutics, BioTheryX, BeiGene, Roche/Genentech, AbbVie; Financial Interests, Other, Consultant (uncompensated): Bayer, GRAIL, Novartis, Vincerx Pharma, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, TH Therapeutics, Incyte. W. Yu: Financial Interests, Full or part-time Employment: Genentech Inc.; Financial Interests, Full or part-time Employment: Genentech; Financial Interests, Stocks/Shares: Roche. W. Yu: Full or part-time Employment: Genentech Inc. J. Malato: Financial Interests, Full or part-time Employment: Genentech; Financial Interests, Stocks/Shares: Roche. R. Price: Financial Interests, Full or part-time Employment: Genentech; Financial Interests, Stocks/Shares: Roche. W. Darbonne: Financial Interests, Full or part-time Employment: Genentech; Financial Interests, Stocks/Shares: Roche. T.M. Szado: Financial Interests, Full or part-time Employment: Genentech; Financial Interests, Stocks/Shares: F. Hoffmann-La Roche. K. Schulze: Financial Interests, Full or part-time Employment: Genentech; Financial Interests, Stocks/Shares: Roche. C.J. Sweeney: Financial Interests, Personal, Advisory Board, Consultancy: Genentech-Roche, Bayer, Astellas, Pfizer, Pfizer, Sanofi, Lilly; Financial Interests, Personal, Other, Consultancy: Janssen; Financial Interests, Personal, Stocks/Shares: Leuchemix; Financial Interests, Institutional, Research Grant: Bayer, Janssen, Astellas, Pfizer, Dendreon, Sanofi. J. Hainsworth: Financial Interests, Institutional, Funding, For conduct of MyPathway, paid to institution: Genentech. F. Meric-Bernstam: Financial Interests, Personal, Other, Consultant: AstraZeneca, DebioPharm, eFFECTOR Therapeutics, F. Hoffman-La Roche Ltd., Tyra Biosciences, Xencor, Zymeworks, OnCusp Therapeutics; Financial Interests, Personal, Advisory Board, Advisory Board/Consultant: Seagen; Financial Interests, Personal, Advisory Board: Silverback Therapeutics, Zentalis, Karyopharm, Biovica, Eisai; Financial Interests, Personal, Other, Consulting: Tallac Therapeutics, Lengo Therapeutics, Loxo-Oncology, Black Diamond, Infinity Pharmaceuticals, AbbVie; Financial Interests, Institutional, Other, Local PI / Research Grant: Aileron Therapeutics, Bayer Healthcare, CytomX Therapeutics Inc., Daiichi Sankyo Co. Ltd., eFFECTOR Therapeutics, Taiho Pharmaceutical Co.; Financial Interests, Institutional, Other, Local PI / Research Grant / Coordinating PI: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Calithera Biosciences, Curis Inc., Debiopharm International, Guardant Health Inc., Klus Pharma, Novartis, PPD Investigator Services; Financial Interests, Institutional, Other, Local PI / Steering Committee Member: Genentech Inc.; Financial Interests, Institutional, Research Grant: Takeda Pharmaceutical Co., Puma Biotechnology Inc., Repare. R. Kurzrock: Financial Interests, Funding, Research funding: Biological Dynamics, Boehringer Ingelheim, Debiopharm, Foundation Medicine, Genentech, Grifols, Guardant, Incyte, Konica Minolta, MedImmune, Merck Serono, Omniseq, Pfizer, Sequenom, Takeda, TopAlliance; Financial Interests, Advisory Role, Consultant and/or speaker fees and/or served on an advisory board: Actuate Therapeutics, AstraZeneca, Bicara Therapeutics, Biological Dynamics, Eisai, EOM Pharmaceuticals, Iylon, Merck, NeoGenomics, Neomed, Pfizer, Prosperdtx, Roche, TD2/Volastra, Turning Point Therapeutics, X-Biotech; Financial Interests, Stocks/Shares: CureMatch Inc., CureMetrix, IDbyDNA; Financial Interests, Other, Board member: CureMatch, CureMetrix; Financial Interests, Other, Co-founder: CureMatch.