HER-2 R678Q

P1, N=30, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

P2, N=102, Active, not recruiting, AstraZeneca | Trial completion date: Jan 2028 --> Jul 2026

P1, N=30, Recruiting, National Cancer Institute (NCI) | N=18 --> 30

In heavily pretreated pts with limited Tx options, T-DXd demonstrated encouraging anticancer activity and long DoR across multiple tumor types with HER2m and a range of HER2 expression levels, with a known safety profile. Translational research will help characterize pts who may derive greatest benefit from T-DXd.

Among patients with any ERBB2 mutations, 7 received a combination of chemotherapy plus anti-EGFR, either cetuximab or panitumumab, 6 had PR and 1 SD as best response. In this consecutive real-world series, ERBB2 activating mutation prevalence was 3.1%. We found an addition 4.4% ERBB2 VUS prevalence, with a ERBB2 mutation prevalence of 7.5% as a whole. Pathogenetic mutations can co-occur with other driver molecular alterations.

The overall variation rate of ERBB2 is 5.4% in Chinese patients with CRC, which is accompanied by significantly different molecular pathological characteristics compared to patients with wild-type ERBB2, and different mutation types (CNV or SNV) display different molecular pathological characteristics.

P2, N=25, Completed, City of Hope Medical Center | Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Sep 2022

HER2 mutations are most common in EC among gynecologic cancers, with R678Q most frequent in our cohort, and T862A in cBioportal. While no HER2 -mutated tumors had a 3+ IHC score, increased HER2 expression (2+) was seen in tumors with L313V, R678Q, and T862A mutations, and HER2 rearrangement. Targeted therapy has already been applied in other tumor types with these HER2 mutations; however, further studies are necessary to explore the prognostic and therapeutic implications of these findings in gynecologic cancers.

P1/2, N=91, Terminated, Black Diamond Therapeutics, Inc. | Completed --> Terminated; The development of BDTX-189 was discontinued by the sponsor.

P1/2, N=91, Completed, Black Diamond Therapeutics, Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Sep 2022 | Trial primary completion date: Jun 2023 --> Sep 2022

Prior treatments included platinum-based chemotherapy (100%), bevacizumab (73%), and pembrolizumab (18%). No patients discontinued treatment due to diarrhea. Table: 559P CBR, CR + PR + SD ≥16 weeks; CR, complete response; DoR, duration of response; NE, not estimable; ORR, objective response rate; PFS, progression-free survival; PR, partial response; SD, stable disease Conclusions These encouraging results support the clinical benefit of neratinib in this patient population and warrant further investigation following platinum failure.