Abstract 79TiP
Background
HER2 mutations are present in 2–4% of NSCLC tumors; of these ∼50% are exon 20 insertion (ex20ins) mutations. There is an unmet need for effective targeted therapy against HER2 mutations in solid tumors, particularly in NSCLC. BI 1810631 is a HER2 selective TKI that covalently binds to both wild-type/mutated HER2 receptors, including ex20ins, whilst sparing EGFR signaling; preclinical data suggest good tolerability and efficacy. This phase Ia/Ib, open-label, non-randomized study aims to determine safety, MTD, PK, pharmacodynamics, and preliminary efficacy of BI 1810631 in pts with HER2+ solid tumors (NCT04886804).
Trial design
∼96 pts from 3 sites in the US, Netherlands, and Japan will be recruited. Phase Ia: consecutive cohorts of pts will receive BI 1810631 QD or BID at escalating doses. Starting dose level: 15 mg BID; QD schedule will begin after one dose level above estimated therapeutic dose of BI 1810631 is determined safe by the Dose Escalation Committee (expected starting dose: 60 mg). BI 1810631 dose escalation will continue until MTD and/or RP2D is determined, as well as preferred phase Ib schedule. Phase Ib: an initial 30 pts with HER2 ex20ins mutation-positive, pre-treated NSCLC will be enrolled, with possible inclusion of additional cohorts in the future. Inclusion criteria (Phase Ia): ≥18 years of age; histologically/cytologically confirmed HER2+ advanced, unresectable and/or metastatic solid tumors refractory/not suitable for standard therapy; exhausted treatment options; measurable or evaluable lesions (according to RECIST v1.1); ECOG PS ≤1. Phase Ib criteria: HER2 ex20ins mutation-positive NSCLC; received ≥1 line of platinum-based combination chemotherapy in the advanced/metastatic setting. Primary endpoints: MTD based on the number of DLTs/number of pts with DLTs (Phase Ia); objective response (Phase Ib). Secondary endpoints: number of pts with DLTs throughout entire treatment period and PK parameters (Phase Ia/Ib); duration of response, PFS, disease control, and duration of disease control (Phase Ib). The trial is actively recruiting; 5 pts have been enrolled to date and 2 dose levels have been completed.
Clinical trial identification
NCT04886804.
Editorial acknowledgement
Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Rick Burgon, of Ashfield MedComms, an Ashfield Health Company, during the development of this abstract.
Legal entity responsible for the study
Boehringer Ingelheim.
Funding
Boehringer Ingelheim.
Disclosure
F. Opdam: Other, Institutional, Invited Speaker, relationship with this company is relevant to the abstract presentation: Boehringer Ingelheim; Other, Institutional, Principal Investigator, relationship with this company is relevant to the abstract presentation: Boehringer Ingelheim; Other, Institutional, Principal Investigator, relationship with this company is not relevant to the abstract presentation: AstraZeneca; Other, Institutional, Principal Investigator, relationship with this company is not relevant to the abstract presentation: GSK; Other, Institutional, Principal Investigator, relationship with this company is not relevant to the abstract presentation: Cytovation; Other, Institutional, Principal Investigator, relationship with this company is not relevant to the abstract presentation: InteRNA technologies; Other, Institutional, Principal Investigator, relationship with this company is not relevant to the abstract presentation: Merus; Other, Institutional, Principal Investigator, relationship with this company is not relevant to the abstract presentation: Taiho; Other, Institutional, Principal Investigator, relationship with this company is not relevant to the abstract presentation: Pierre-Fabre. J. Heymach: Financial Interests, Personal, Advisory Board, the relationship with this company is not relevant to the abstract presentation: AstraZeneca; Financial Interests, Personal, Advisory Board, the relationship with this company is not relevant to the abstract presentation: EMD Serono; Financial Interests, Personal, Advisory Board, the relationship with this company is not relevant to the abstract presentation: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board, the relationship with this company is not relevant to the abstract presentation: Catalyst; Financial Interests, Personal, Advisory Board, the relationship with this company is not relevant to the abstract presentation: Genentech; Financial Interests, Personal, Advisory Board, the relationship with this company is not relevant to the abstract presentation: GlaxoSmithKlein; Financial Interests, Personal, Advisory Board, the relationship with this company is not relevant to the abstract presentation: Hengrui Therapeutics; Financial Interests, Personal, Advisory Board, the relationship with this company is not relevant to the abstract presentation: Eli Lilly; Financial Interests, Personal, Advisory Board, the relationship with this company is not relevant to the abstract presentation: Spectrum; Financial Interests, Personal, Advisory Board, the relationship with this company is not relevant to the abstract presentation: Sanofi; Financial Interests, Personal, Advisory Board, the relationship with this company is not relevant to the abstract presentation: Takeda; Financial Interests, Personal, Advisory Board, the relationship with this company is not relevant to the abstract presentation: Mirati Therapeutics; Financial Interests, Personal, Advisory Board, the relationship with this company is not relevant to the abstract presentation: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, the relationship with this company is not relevant to the abstract presentation: BrightPath Biotherapeutics; Financial Interests, Personal, Advisory Board, the relationship with this company is not relevant to the abstract presentation: Janssen Global Services; Financial Interests, Personal, Advisory Board, the relationship with this company is not relevant to the abstract presentation: Nexus Health Systems; Financial Interests, Personal, Advisory Board, the relationship with this company is not relevant to the abstract presentation: Pneuma Respiratory; Financial Interests, Personal, Advisory Board, the relationship with this company is not relevant to the abstract presentation: Kairos Venture Investments; Financial Interests, Personal, Advisory Board, the relationship with this company is not relevant to the abstract presentationthe relationship with this company is not relevant to the abstract presentation: Roche; Financial Interests, Personal, Advisory Board, the relationship with this company is not relevant to the abstract presentation: Leads Biolabs; Financial Interests, Personal, Advisory Board, the relationship with this company is not relevant to the abstract presentation: RefleXion; Financial Interests, Personal, Advisory Board, the relationship with this company is not relevant to the abstract presentation: Chugai Pharmaceuticals; Financial Interests, Personal, Full or part-time Employment, the relationship with this company is not relevant to the abstract presentation: The University of Texas MD Anderson Cancer Center; Financial Interests, Institutional, Licensing Fees, the relationship with this company is not relevant to the abstract presentation: Spectrum; Financial Interests, Institutional, Royalties, the relationship with this company is not relevant to the abstract presentation: Spectrum; Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: AstraZeneca; Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: Spectrum; Financial Interests, Institutional, Project Lead, the relationship with this company is not relevant to the abstract presentation: Lung SPORE; Financial Interests, Institutional, Project Lead, the relationship with this company is not relevant to the abstract presentation: Cancer Prevention & Research Institute of Texas (CPRIT); Financial Interests, Institutional, Principal Investigator, the relationship with this company is not relevant to the abstract presentation: Lung SPORE; Financial Interests, Institutional, Principal Investigator, the relationship with this company is not relevant to the abstract presentation: NIH/NCI; Financial Interests, Institutional, Principal Investigator, the relationship with this company is not relevant to the abstract presentation: Cancer Prevention & Research Institute of Texas (CPRIT); Financial Interests, Institutional, Principal Investigator, the relationship with this company is not relevant to the abstract presentation: Emerson Collective; Financial Interests, Institutional, Principal Investigator, the relationship with this company is not relevant to the abstract presentation: Bristol Myers Squibb; Financial Interests, Institutional, Principal Investigator, the relationship with this company is not relevant to the abstract presentation: AstraZeneca; Financial Interests, Institutional, Principal Investigator, the relationship with this company is not relevant to the abstract presentation: Spectrum. N. Gibson: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. B. Sadrolhefazi: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. J. Serra: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. N. Yamamoto: Financial Interests, Personal, Speaker’s Bureau, the relationship with this company is not relevant to the abstract presentation: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau, the relationship with this company is not relevant to the abstract presentation: Eli Lilly; Financial Interests, Personal, Speaker’s Bureau, the relationship with this company is not relevant to the abstract presentation: ONO; Financial Interests, Personal, Speaker’s Bureau, the relationship with this company is not relevant to the abstract presentation: Chugai; Financial Interests, Personal, Speaker’s Bureau, the relationship with this company is not relevant to the abstract presentation: Sysmex; Financial Interests, Personal, Speaker’s Bureau, the relationship with this company is not relevant to the abstract presentation: Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau, the relationship with this company is not relevant to the abstract presentation: Eisai; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: Astellas; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: Chugai; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: Eisai; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: Taiho; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: Bristol Myers Squibb; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: Pfizer; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: Novartis; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: Eli Lilly; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: AbbVie; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: Daiichi Sankyo; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: Bayer; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: Kyowa-Hakko Kirin; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: Takeda; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: ONO; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: Janssen Pharma; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: MSD; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: MERCK; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: GSK; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: Sumitomo Dainippon; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: Chiome Bioscience; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: Otsuka; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: Carna Biosciences; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: Genmab; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is not relevant to the abstract presentation: Shionogi; Non-Financial Interests, Institutional, Research Grant, the relationship with this company is relevant to the abstract presentation: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role, the relationship with this company is not relevant to the abstract presentation: Eisai; Financial Interests, Personal, Advisory Role, the relationship with this company is not relevant to the abstract presentation: Takeda; Financial Interests, Personal, Advisory Role, the relationship with this company is not relevant to the abstract presentation: Otsuka; Financial Interests, Personal, Advisory Role, the relationship with this company is not relevant to the abstract presentation: Cimic; Financial Interests, Personal, Advisory Role, the relationship with this company is not relevant to the abstract presentation: Chugai; Financial Interests, Personal, Advisory Role, the relationship with this company is relevant to the abstract presentation: Boehringer Ingelheim. All other authors have declared no conflicts of interest.