642P - Phase I study of SHR-A2009, a HER3-targeted ADC, in pretreated EGFR-mutated NSCLC

Background

SHR-A2009 is a novel ADC composed of a fully human anti-HER3 IgG1 mAb, cleavable peptide linker and DNA topoisomerase I inhibitor. We conducted a first-in-human, multinational phase 1 trial of SHR-A2009 in patients (pts) with pretreated advanced solid tumors, and here report the efficacy and safety in pts with advanced EGFR-mutated NSCLC.

Methods

The study composed of dose-escalation (i3+3 design), dose-expansion and indication-expansion phases, during which pts received SHR-A2009 at doses of 1.5-12.0 mg/kg (Q3W, iv). One of the indication-expansion cohorts evaluated pts with EGFR-mutated NSCLC. Dose optimization in the dose range of 6.0 mg/kg ∼ 9.0 mg/kg is ongoing.

Results

As of data cutoff (Mar 30, 2024), 103 pts with EGFR-mutated NSCLC were enrolled and treated. Median follow-up was 8.6 mo. Median prior lines of systemic therapy was 2 (1-7). All pts had been previously treated with EGFR-TKI, with 88.3% receiving a 3^rd generation EGFR-TKI; chemotherapy was received by 64.1%, with 59.2% receiving platinum-based chemotherapy (PBC). Among pts treated at an expansion dose of 9.0 mg/kg (n=52), the ORR was 46.9% (23/49; 95% CI 32.5-61.7) and DCR was 93.9% (46/49; 95% CI 83.1-98.7) in the evaluable set; the responses with SHR-A2009 were durable (see table). Tumor response in all dose cohorts is shown in the table. Considering all treated pts, median PFS was 9.6 mo (95% CI 5.7-12.4) in the 9.0 mg/kg cohort and 6.7 mo (95% CI 4.8-9.7) in all dose cohorts. Overall, grade ≥3 TRAEs were reported in 56.3% of 103 pts, with all occurring in ≥5% being hematotoxicities. TRAEs led to drug discontinuation in 8.7% of pts. Interstitial lung disease occurred in 8.7% of pts. Table: 642P

Tumor response (evaluable set)

^∗Including unconfirmed responses (n=3). All of the pts achieved confirmed response by the data cutoff of Apr. 30, 2024. ^†Kaplan-Meier method.

Conclusions

SHR-A2009 showed encouraging anti-tumor activity and a tolerable safety profile in pts with EGFR-mutated NSCLC progressing after EGFR-TKI. Further investigations are warranted.

Clinical trial identification

NCT05114759.

Editorial acknowledgement

Legal entity responsible for the study

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Funding

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Disclosure

Q. Zhou: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Lilly, Roche, Pfizer, Boehringer Ingelheim, MSD Oncology, Bristol Myers Squibb, Hengrui. Y. Wu: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Boehringer Ingelheim, BeiGene, Hengrui, Merck, MSD, Pfizer, Roche, Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Takeda, Amgen, Daiichi Sankyo; Financial Interests, Coordinating PI: AstraZeneca, Boehringer Ingelheim, BMS, Hengrui, Merck, MSD, Pfizer, Roche, Eli Lilly; Financial Interests, Steering Committee Member: Sanofi, Yunhan; Non-Financial Interests, Leadership Role: Chinese Thoracic Oncology Group (CTONG); Non-Financial Interests, Other, WCLC 2020 Conference Chair: IASLC; Non-Financial Interests, Leadership Role, Past President: Chinese Society of Clinical Oncology (CSCO); Non-Financial Interests, Other, Editorial Board member of Ann Oncology and ESMO Open: ESMO. N. Yamamoto: Financial Interests, Personal, Advisory Role: Eisai, Takeda, Boehringer Ingelheim, Cmic, Chugai, Merck, Healios; Financial Interests, Personal, Speaker’s Bureau: Chugai, Daiichi Sankyo, Eisai ; Financial Interests, Institutional, Research Grant: Astellas, Chugai, Eisai, Taiho, BMS, Pfizer, Novartis, Eli Lilly, AbbVie, Daiichi Sankyo, Bayer, Boehringer Ingelheim, Kyowa Kirin, Takeda, Ono, Janssen Pharma, MSD, Merck, GSK, Sumitomo Pharma, Chiome Bioscience, Otsuka, Carna Biosciences, Genmab, Shionogi, Toray, Kaken, AstraZeneca, Cmic, InventisBio, Rakuten Medical. Y. Kuboki: Financial Interests, Personal, Advisory Board: Takeda, Amgen, Abbie, Incyte, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Taiho, Lilly; Financial Interests, Institutional, Local PI: Taiho, Astelas, Lilly, Takeda, AstraZeneca, Boehringer Ingelheim, Chugai, Genmab, Incyte, Abbie, Merck, Novartis, Hengrui; Financial Interests, Institutional, Coordinating PI: Amgen; Non-Financial Interests, Member: JSMO, ASCO, JSCO, JCA. S. Han: Financial Interests, Institutional, Local PI: Hanmi, Genentech, Roche, Loxo, Mirati, MSD, Janssen, Lilly, Seagen, Arcus. Z. Wang, F. Qiu, L. Yang: Financial Interests, Personal, Full or part-time Employment: Hengrui. All other authors have declared no conflicts of interest.