1036P - A phase I/IIa first-in-human study of PM1003 (anti-PD-L1 x 4-1BB bispecific antibody) in patients with advanced solid tumors

Background

PM1003 is a VHH-based anti-PD-L1 x 4-1BB bispecific antibody that exhibits PD-L1 expression-dependent 4-1BB agonism, with excellent anti-tumor activity and safety in preclinical studies.

Methods

The safety and tolerability of PM1003 in patients (pts) with advanced solid tumors were assessed during dose escalation, and pts with advanced solid tumors positive for PD-L1 expression have been enrolled for assessing anti-tumor activity during dose expansion.

Results

At the data cut-off up to Apr. 19, 2023, 23 pts had been enrolled, with 19 pts for dose escalation (3 pts for each of the 0.02, 0.1, 1, 3, 10 mg/kg dose levels and 4 pts for the 6 mg/kg dose level). All pts had prior 1-6 lines of systemic treatment. Dose-limiting toxicity (DLT) was assessed over 21 days after the first dose followed by dosing Q2W. 4 pts were enrolled for dose expansion (2 pts in 1 mg/kg, 1 patient in each of the 3 and 6 mg/kg dose levels, Q2W). No DLTs were observed during dose escalation. Treatment-related adverse events (TRAEs) occurred in 22 pts (95.7%). The most common TRAEs in pts included anemia (39.1%, Grade≥3 0%), aspartic acid aminotransferase increased (30.4%, Grade≥3 4.3%), white blood cell count decreased (30.4%, Grade≥3 8.7%) and platelet count decreased (30.4%, Grade≥3 0%). For the 1 - 10 mg/kg cohorts, T_1/2 was 6.3 - 15.3 days after the first dose. PD-L1 target occupancy approach to saturation at 7 days after the first dose and maintained stable. 18 pts were evaluable for efficacy. The objective response rate was 5.6% and the disease control rate was 44.4%. Preliminary antitumor activity was observed in one PD-L1 positive gastric cancer patient (1 mg/kg, Q2W; TPS=5%, CPS=30) who was heavily treated with chemotherapy, anti-PD-1 and anti-HER2-ADC after surgery. 87.8% of tumor shrinkage was achieved in the target lesion at the first efficacy evaluation (7 weeks) after PM1003 treatment. Partial Response was confirmed at subsequent visits.

Conclusions

PM1003 was well-tolerated at doses up to 10 mg/kg and preliminary antitumor efficacy was observed in a patient with prior anti-PD-1 treatment. Expansion cohorts to evaluate efficacy and further safety in PD-L1-positive pts are ongoing.

Clinical trial identification

ChiCTR2100052887.

Editorial acknowledgement

Legal entity responsible for the study

Biotheus Inc.

Funding

Biotheus Inc.

Disclosure

All authors have declared no conflicts of interest.