TY - JOUR
T1 - A Phase I, Open-Label, Dose Confirmation, Escalation, and Expansion Trial of BI 1810631 as Monotherapy in Patients With Advanced or Metastatic Solid Tumors With HER2 Aberrations
AU - Heymach, John
AU - Opdam, Frans
AU - Barve, Minal
AU - Gibson, Neil
AU - Sadrolhefazi, Behbood
AU - Serra, Josep
AU - Yamamoto, Noboru
N1 - Funding Information:
Medical writing support for the development of this manuscript, under the direction of the authors, was provided by Lynn Pritchard, of Ashfield MedComms, an Inizio Company, and funded by Boehringer Ingelheim. The study was sponsored by Boehringer Ingelheim. Authors did not receive payment related to the development of the manuscript.
Funding Information:
John Heymach reports the receipt of advisory/consulting fees from Bristol Myers Squibb, GlaxoSmithKline, Kairos Venture Investments, BrightPathTherapeutics, Hengrui Therapeutics, Eli Lilly, EMD Serono, Foundation One Medicine, Spectrum, AstraZeneca; receipt of research funding from NIH/NCI, American Cancer Society, Checkmate Pharmaceuticals, AstraZeneca, Spectrum; and royalties and patents from Spectrum. Neil Gibson, Behbood Sadrolhefazi and Josep Serra are employees of Boehringer Ingelheim. Noboru Yamamoto reports the receipt of research grants as a Principal Investigator from Astellas, Chugai, Eisai, Taiho, Bristol Myers Squibb, Pfizer, Novartis, Eli Lilly, AbbVie, Daiichi-Sankyo, Bayer, Boehringer Ingelheim, Kyowa-Hakko Kirin, Takeda, ONO, Janssen Pharma, MSD, MERCK, GSK, Sumitomo Dainippon, Chiome Bioscience, Otsuka, Carna Biosciences, Genmab; an advisory role with Eisai, Takeda, Otsuka, Boehringer Ingelheim, Cimic, Chugai; honoraria as a speakers from AstraZeneca, Eli Lilly, ONO, Chugai, Sysmex, Daiichi-Sankyo, Eisai. Frans Opdam and Minal Barve report no conflicts of interest.
Publisher Copyright:
© 2022 The Authors
PY - 2023/3
Y1 - 2023/3
N2 - Background: BI 1810631 is a human HER2-selective tyrosine kinase inhibitor that covalently binds to both wild-type and mutated HER2 receptors, including exon 20 insertion mutations, whilst sparing EGFR signaling. This phase Ia/Ib, open-label, non-randomized study will determine the safety, maximum tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of BI 1810631 in patients with HER2 aberration-positive solid tumors (NCT04886804). Patients and Methods: In phase Ia, patients with histologically/cytologically confirmed HER2 aberration-positive advanced/metastatic solid tumors will receive BI 1810631 orally twice daily (BID) or once daily (QD) at escalating doses. Starting dose level is 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. Dose escalation will continue until MTD/recommended phase II dose and preferred phase Ib schedule for each schedule is determined. In phase Ib, patients with HER2 tyrosine kinase domain (TKD) mutation-positive non-small cell lung cancer (NSCLC) who have previously received ≥1 line of systemic therapy will be enrolled initially, with possible inclusion of additional NSCLC cohorts in the future, including untreated patients. The primary endpoints will be MTD based on number of dose-limiting toxicities (DLTs)/number of patients with DLTs (phase Ia) and objective response (phase Ib). Secondary endpoints include PK parameters (phase Ia/Ib); duration of response, disease control, duration of disease control, and progression-free survival (phase Ib). Conclusions: BI 1810631 could be an effective and tolerable EGFR-sparing oral treatment for patients with HER2 mutation-positive NSCLC, including exon 20 insertion mutations. ClinicalTrials.gov identifier: NCT04886804.
AB - Background: BI 1810631 is a human HER2-selective tyrosine kinase inhibitor that covalently binds to both wild-type and mutated HER2 receptors, including exon 20 insertion mutations, whilst sparing EGFR signaling. This phase Ia/Ib, open-label, non-randomized study will determine the safety, maximum tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of BI 1810631 in patients with HER2 aberration-positive solid tumors (NCT04886804). Patients and Methods: In phase Ia, patients with histologically/cytologically confirmed HER2 aberration-positive advanced/metastatic solid tumors will receive BI 1810631 orally twice daily (BID) or once daily (QD) at escalating doses. Starting dose level is 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. Dose escalation will continue until MTD/recommended phase II dose and preferred phase Ib schedule for each schedule is determined. In phase Ib, patients with HER2 tyrosine kinase domain (TKD) mutation-positive non-small cell lung cancer (NSCLC) who have previously received ≥1 line of systemic therapy will be enrolled initially, with possible inclusion of additional NSCLC cohorts in the future, including untreated patients. The primary endpoints will be MTD based on number of dose-limiting toxicities (DLTs)/number of patients with DLTs (phase Ia) and objective response (phase Ib). Secondary endpoints include PK parameters (phase Ia/Ib); duration of response, disease control, duration of disease control, and progression-free survival (phase Ib). Conclusions: BI 1810631 could be an effective and tolerable EGFR-sparing oral treatment for patients with HER2 mutation-positive NSCLC, including exon 20 insertion mutations. ClinicalTrials.gov identifier: NCT04886804.
KW - EGFR-sparing
KW - ex20ins
KW - HER2-selective
KW - NSCLC
KW - TKD
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U2 - 10.1016/j.cllc.2022.10.008
DO - 10.1016/j.cllc.2022.10.008
M3 - Article
C2 - 36528522
AN - SCOPUS:85144562317
SN - 1525-7304
VL - 24
SP - e65-e68
JO - Clinical Lung Cancer
JF - Clinical Lung Cancer
IS - 2
ER -