Efficacy and safety of PM8002, a bispecific antibody targeting PD-L1 and VEGF-A, as a monotherapy in patients with solid tumors: Clinical data from advanced cervical cancer and platinum-resistant recurrent ovarian cancer cohorts.

5524 Background: The effectiveness of immune checkpoint inhibitors for treating patients with advanced cervical cancer or platinum-resistant recurrent ovarian cancer (PROC) has been demonstrated in clinical studies. However, the current treatment options have not fully met the clinical needs of these patients. Since 2021, a Phase Ib/IIa trial was conducted in China to assess the safety and efficacy of PM8002, a bispecific antibody that targets both PD-L1 and VEGF-A, as a monotherapy in patients with solid tumors. Preliminary clinical data was presented at SITC2022 (abstract #725) and ASCO2023 (abstract #2536). Here, we present an update of our study for cervical cancer and PROC cohorts. Methods: Patients with cervical cancer (1 st or 2 nd line therapy) or PROC (received at most one line therapy after platinum resistance) were enrolled after completion of dose escalation. In these two cohorts, patients received PM8002 until observation of unacceptable toxicity or disease progression. Tumor responses were evaluated every 6 weeks. The primary endpoint was objective response rate (ORR) with secondary endpoints that included safety. Results: As of December 20, 2023, 366 eligible patients were enrolled and received at least one dose of PM8002, including 48 patients with advanced cervical cancer and 39 patients with PROC. Among 45 evaluable patients with cervical cancer, 1 complete response (CR), 18 partial responses (PR) and 23 patients with stable disease (SD) were observed leading to an ORR of 42.2% (19/45) and disease control rate (DCR) of 93.3% (42/45). The median progression-free survival (PFS) was 8.3 months and 6-month PFS was 61.4%. The ORR of patients with PD-L1-positive tumors (CPS≥1) was 52.4% (11/21). Among 34 evaluable PROC patients, 7 PRs and 16 SDs were observed with an ORR of 20.6% (7/34) and DCR of 67.7% (23/34). The mPFS was 5.3 months with a 6-month PFS of 37.2%. In these two cohorts, any-grade treatment-related adverse events (TRAE) occurred in 95.4% of patients (85/87) with ≥ Grade 3 TRAEs at 35.6% (31/87). Any-grade immune-related adverse events (irAE) occurred in 57.5% (50/87) of patients with ≥ Grade 3 irAEs at 8% (7/87). Serious adverse events (SAE) and treatment-related SAEs were observed in 33.3% (29/87) and 25.3% (22/87) of patients, respectively. The most common TRAEs (≥15.0%) were proteinuria, hypertension, anemia, white blood cell counts increase and thrombocytosis. 14.9% (13/87) of patients discontinued PM8002 administration due to TRAEs. Conclusions: PM8002 showed promising antitumor activity as a monotherapy in previously treated patients with PROC or cervical cancer. In addition to monotherapy studies, multiple Phase II combination trials of PM8002 with chemotherapy are ongoing. Clinical trial information: NCT05918445 .