1992P - A phase II safety and efficacy study of PM8002 (anti-PD-L1 x VEGF-A bispecific) combined with paclitaxel as a second-line therapy for small cell lung cancer (SCLC)

Background

There is an unmet medical need for SCLC patients that progress on or after first-line platinum-based therapy. PM8002 is a bispecific antibody targeting PD-L1 and VEGF-A. Here, we present our results from a phase II study of PM8002 in combination with paclitaxel as second-line treatment for SCLC.

Methods

Subjects with advanced SCLC who failed first-line platinum-based chemotherapy with or without checkpoint inhibitors therapy were enrolled for assessing the safety and efficacy of PM8002 in combination with paclitaxel. Primary endpoints included safety (CTCAE v5.0) and ORR (RECIST v1.1). All subjects received PM8002 (30 mg/kg Q3W) and paclitaxel (175 mg/m² Q3W) for 5 cycles, followed by PM8002 maintenance (30 mg/kg Q3W) until unacceptable toxicity or disease progression.

Results

As of April 21, 2023, 27 subjects (26 without and 1 with previous immunotherapy) had been enrolled. Among 26 immunotherapy naïve subjects, 26 and 22 subjects were evaluable for safety and efficacy, respectively. Overall ORR was 72.7% (16/22) with a DCR of 81.8% (18/22). Median PFS was 5.5 months (95% CI, 2.8 - NR. 11 out of 22 subjects were still on treatment and PFS were censored accordingly). Any-grade TEAEs occurred in 96.2% (25/26) of subjects. Grade ≥ 3 TEAEs related to the combination regimen occurred in 73.1% (19/26) of subjects, with the most common grade ≥ 3 TRAEs observed as neutropenia (53.8%, 14/26) and leukopenia (34.6%, 9/26). One patient discontinued PM8002 and/or paclitaxel administration due to TRAEs. Any-grade immune-related adverse events (irAEs) occurred in 30.8% (8/26) of subjects, and grade ≥ 3 irAEs occurred in 4% (1/26) of subjects, which was a grade 3 proteinuria. The first efficacy/safety evaluation for the subject with previous immunotherapy was pending. Recruitment for immunotherapy failure subjects is still ongoing.

Conclusions

PM8002, in combination with paclitaxel, showed encouraging antitumor activity and an acceptable safety profile for patients with advanced SCLC who failed first-line platinum-based chemotherapy. This phase II study is still ongoing and shall include more patients who had previously received immune checkpoint therapy.

Clinical trial identification

ChiCTR2200059911.

Editorial acknowledgement

Legal entity responsible for the study

Biotheus Inc.

Funding

Biotheus Inc.

Disclosure

All authors have declared no conflicts of interest.