1255MO - A phase II safety and efficacy study of PM8002/BNT327 in combination with chemotherapy in patients with EGFR-mutated non-small cell lung cancer (NSCLC)

Background

PM8002/BNT327 is a bispecific antibody targeting PD-L1 and VEGF-A. Here we present data from an ongoing single-arm Phase II study of PM8002/BNT327 combined with chemotherapy for patients with EGFR-mutated NSCLC who progressed after EGFR-TKI treatment. The correlation between tumor PD-L1 expression and clinical response was investigated.

Methods

Patients received PM8002/BNT327 plus carboplatin and pemetrexed Q3W for 4 cycles, followed by maintenance with PM8002/BNT327 and pemetrexed. The primary endpoint is ORR (RECIST v1.1). Analysis by PD-L1 expression was determined by immunohistochemistry (IHC with E1L3N clone; using tumor proportion score (TPS)) in biopsy taken after progression on EGFR-TKI therapy and classified based on TPS as negative (＜1%), low expression (1 to 49%), or high expression (≥50%).

Results

As of April 12, 2024, 64 patients were tested for PD-L1 TPS: 28 (43.8%) were TPS＜1%, 23 (35.9%) were TPS 1-49%, and 13 (20.3%) were TPS ≥50%. All patients were evaluable for safety and efficacy. Overall ORR was 54.7% (35/64, 95% CI:41.8-67.2) and DCR was 95.3% (61/64, 95% CI:86.9-99.0). In the PD-L1 TPS＜1% group, the ORR was 35.7% (95% CI:18.6-55.9) and DCR was 92.9% (95% CI:76.5-99.1). In the TPS 1-49% group, the ORR was 56.5% (95% CI:34.5-76.8) and DCR was 100% (95% CI:85.2-100.0). In the TPS ≥50% group, the ORR was 92.3% (95% CI:64.0-99.8) and DCR was 92.3% (95% CI:64.0-99.8). Any-grade treatment-related adverse events (TRAEs) occurred in 95.3% (61/64) and grade ≥ 3 TRAEs occurred in 54.7% (35/64) patients. Any-grade immune-related AEs (irAEs) occurred in 28.1% (18/64) and grade ≥ 3 irAEs occurred in 4.7% (3/64) patients. 6 patients discontinued PM8002 and/or chemotherapy administration due to TRAEs with 1 TRAE-related death.

Conclusions

PM8002/BNT327 in combination with chemotherapy showed encouraging antitumor activity and acceptable tolerability profile in EGFR-mutated NSCLC patients that progressed after EGFR-TKI therapy. The anti-tumor activity of PM8002/BNT327 therapy is positively correlated with tumor PD-L1 expression level.

Clinical trial identification

NCT05756972.

Editorial acknowledgement

Legal entity responsible for the study

Biotheus Inc.

Funding

Biotheus Inc.

Disclosure

All authors have declared no conflicts of interest.