Preliminary results of GQ1005 in metastatic HER2-low expressing breast cancer and HER2 positive gastric cancer

BackgroundGQ1005 is an innovative anti-HER2 antibody-drug conjugate (ADC) processed through a novel, integrated and stable enzyme conjugation links DXd to engineered trastuzumab, the drug-to-antibody ratio is 4.MethodsIn the FIH phase 1a/1b study, patients(pts) of HER2 expressing/mutated metastatic solid tumors progressed from the standard of care were included. Dose escalation was ranged from 2 to 9.6 mg/kg (2, 4, 6, 7.2, 8.4 and 9.6 mg/kg). Safety and efficacy were investigated Q3W as well as in the expansion stage.ResultsBy April 19th, 2024, 165 pts were enrolled (the median age 55 [range 34-74] with the median line of prior therapy 3 [range 1-11]), including 55 HER2 positive BC, 35 HER2 low BC, 43 HER2 exon19/20 mutant lung cancer and 26 HER2 expressing (IHC2+/3+) gastric cancer pts. The median exposure time of GQ1005 was 12.0 weeks (3.0-63.7). No DLT was observed up to the highest dose. Only 28 and 14 of the 153 safety evaluable pts had ≥ G3 TRAE (18.3%) and the drug related SAE (9.2%), respectively. TRAEs (>20%) are shown in the table. Tumor response was observed from 4 mg/kg. In 29 efficacy evaluable HER2 low BC pts with the median prior therapies of 3, ORR was 27.6% and DCR was 69.0%, mPFS was 10.4m (2.3-NA) and mDOR was 11.9m (6.1-NA). Of 15 efficacy evaluable HER2 positive GC pts, 14 received trastuzumab, 6 received other HER2 ADCs, and 4 received HER2 TKIs. ORR, DCR and 6-mo PFS rate were 33.3%, 80.0%, and 70.0%, respectively. AE profile of both cohorts was consistent with whole population. Only 1 ILD occurred in each cohort. Table: 644P TRAEs (>20%) All Grade n=153(%) ≥ G3 n=153 (%) Nausea 64 (41.8) 0 AST increased 63 (41.2) 2 (1.3) Anemia 52 (34.0) 6 (3.9) ALT increased 47 (30.7) 1 (0.7) Leukopenia 42 (27.5) 3 (2.0) Thrombocytopenia 39 (25.5) 2 (1.3) Decreased appetite 36 (23.5) 1 (0.7) Neutropenia 35 (22.9) 1 (0.7) Vomiting 32 (20.9) 1 (0.7) ConclusionsGQ1005 demonstrates excellent safety profile and encouraging antitumor activity in HER2 expressing tumors, including heavily treated HER2 low BC and HER2 positive GC. Given the wider therapeutic window and the safer profile of GQ1005, a superior survival benefit could be expected from the patients treated with GQ1005. (Sponsored by GeneQuantum Healthcare (Suzhou) Co., Ltd.).Clinical trial identificationNCT06154343.Editorial acknowledgementGeneQuantum Healthcare (Suzhou) Co., Ltd.Legal entity responsible for the studyGeneQuantum Healthcare (Suzhou) Co., Ltd.FundingGeneQuantum Healthcare (Suzhou) Co., Ltd.DisclosureC. Zhou: Financial Interests, Personal, Advisory role, Consulting fees: Innovent Biologics, Qilu, Hengrui, TopAlliance Biosciences Inc.; Financial Interests, Personal, Other, Payment or honoraria from: Eli Lilly China, Sanofi, Boehringer Ingelheim, Roche, Merck Sharp & Dohme, Qilu, Hengrui, Innovent Biologics, Alice, C-Stone, Luye Pharma, TopAlliance Biosciences Inc., Amoy Diagnostics, AnHeart. All other authors have declared no conflicts of interest.