A phase Ib/II study to assess the safety and preliminary efficacy of PM8002 in combination with nab-paclitaxel in patients with triple-negative breast cancer.

Abstract

e13091 Background: PD-L1 and VEGF play important roles in immune escape and tumor angiogenesis and enhance cancer growth and metastasis. PM8002 is a bispecific antibody targeting PD-L1 and VEGF-A. Here, we present our results from a Phase Ib/II study of PM8002 in combination with nab-paclitaxel in subjects with locally advanced or metastatic triple negative breast cancer without previous systematic treatment. Methods: Sixty subjects with locally advanced or metastatic triple-negative breast cancer (with no previous systematic treatment), shall be enrolled into Phase Ib and II studies for testing the safety and efficacy of PM8002 in combination with nab-paclitaxel. Six subjects were enrolled during Phase Ib with safety as the primary endpoint, with the remaining subjects enrolled for the Phase II study to evaluate both safety and efficacy with ORR as the primary endpoint. Each cycle contains 28 days. All subjects received PM8002 at 20 mg/kg (Q2W) and nab-paclitaxel at 100 mg/m2 on the 1st, 8th, and 15th days of each cycle until unacceptable toxicity or disease progression were observed. Tumor responses were evaluated every 8 weeks. Results: As of February 03, 2023, a total of 25 subjects had received at least 1 dose of PM8002 in combination with nab-paclitaxel, including 6 subjects for Phase Ib and 19 subjects for Phase II. For Phase Ib, all 6 subjects received a full dose of PM8002 and nab-paclitaxel during the first cycle and no adverse events of special interest were observed during the 28-day period. Any-grade treatment emergent adverse events (TEAEs) occurred in 17 subjects (68.0%, 17/25); 3 subjects (12.0%, 3/25) with ≥ Grade 3 TEAEs. TEAEs related to PM8002 occurred in 12 subjects (48.0%, 12/25); 2 subjects (8.0%, 2/25) with ≥ Grade 3 TEAEs. Two subjects (8.0%, 2/25) discontinued PM8002 administration due to treatment-related adverse reactions (TRAEs), such as ascites and hypertension, both may be related to PM8002 and nab-paclitaxel. The most common TRAEs with PM8002 and nab-paclitaxel were anemia (16.0%, 4/25), fever (12.0%, 3/25) and neutropenia (12.0%, 3/25). Any-grade immune-related adverse events (irAEs) occurred in 2 subjects (8.0%, 2/25), such as hyperthyreosis; there was no ≥ Grade 3 irAEs occurred. Thirteen subjects completed at least one efficacy evaluation. Objective response rate (ORR) per RECIST 1.1 was 69.2%, including 9 partial responses (PRs), with 9 PRs occurring during the first evaluation. Three subjects achieved stable disease, with a total disease control rate (DCR) of 92.3%. Twenty-two subjects are still on treatment. Conclusions: PM8002 in combination with nab-paclitaxel showed acceptable safety and encouraging antitumor activity in locally advanced or metastatic triple-negative breast cancer. The Phase II study is still ongoing, and we are actively enrolling subjects to complete the study. Clinical trial information: ChiCTR2200060400 .