511MO - A phase I study of SHR-1701, a bifunctional fusion protein targeting PD-L1 and TGF-β, in patients with advanced non-small cell lung cancer (NSCLC)

Background

PD-L1 and TGF-β play un-redundant roles in tumor escape of immune surveillance. Dual blockade of PD-L1 and TGF-β could reshape the tumor microenvironment. SHR-1701 is a bifunctional fusion protein consisting of an anti-PD-L1 antibody fused to the extracellular domain of TGF-β receptor II. Here, we report results of the clinical expansion part of a phase I study of SHR-1701 in patients (pts) with advanced solid tumors.

Methods

The clinical expansion part included 3 cohorts comprising pts with advanced/metastatic NSCLC: Cohort 1 enrolled pts who had not received systemic chemotherapy, PD-L1 TPS ≥1%; Cohort 2 enrolled pts harboring EGFR mutation who had failed previous standard-of-care EGFR TKIs or for whom no standard EGFR TKIs were available; Cohort 3 enrolled pts who progressed after the recent anti-PD-1/PD-L1 treatment and had received up to 3 previous lines of treatments. Eligible pts were given SHR-1701 30 mg/kg once every 3 weeks. The primary endpoint was objective response rate (ORR; RECIST v1.1).

Results

At data cutoff on June 6, 2023, a total of 131 pts were enrolled (Cohort 1 n=57, Cohort 2 n=41, Cohort 3 n=33). 84.0% of pts were in stage IV and 45.0% had ≥3 metastatic sites. The median follow-up duration was 20.3 (range 0-40), 14.3 (range 1-40), and 14.8 months (range 0-35) in the 3 cohorts, respectively. Antitumor activity results per cohort are listed in the table. Treatment-related adverse events (TRAEs) occurred in 100 pts (76.3%), with the most common ones being increased ALT (15.3%), rash (15.3%), increased AST (12.2%), and anemia (11.5%). Of them, 30 pts (22.9%) had grade ≥3 TRAEs. Serious TRAEs were reported in 26 pts (19.8%). 11 pts (8.4%) discontinued study treatment due to TRAEs. One patient died due to tumor hyper-progression, which was deemed related to study treatment. Table: 511MO

Antitumor activity

*CBR=CR+PR+SD ≥24 weeks. NR=not reached.

Conclusions

SHR-1701 showed encouraging antitumor activity in all three cohorts. The safety profile was tolerable.

Clinical trial identification

NCT03774979.

Editorial acknowledgement

Editorial assistance in the writing of the abstract was provided by Yanwen Wang (Jiangsu Hengrui Pharmaceuticals).

Legal entity responsible for the study

Jiangsu Hengrui Pharmaceuticals.

Funding

Jiangsu Hengrui Pharmaceuticals.

Disclosure

F. Liang, P. Liu: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals. All other authors have declared no conflicts of interest.