PM8002/BNT327 Combo Improves Efficacy and Safety in Metastatic TNBC

Data from a phase 1b/2 study show a 78.6% ORR in patients with metastatic triple-negative breast cancer treated with PM8002/BNT327 plus nab-paclitaxel.

PM8002/BNT327, an investigational bispecific antibody targeting PD-L1 and VEGF-A, combined with nab-paclitaxel (Abraxane) in the first-line therapy of patients with locally advanced or metastatic triple-negative breast cancer (TNBC) yielded clinically meaningful efficacy outcomes and tolerability regardless of PD-L1 status, according to results from a phase 1b/2 study (NCT05918133) shared in a poster at the 2024 San Antonio Breast Cancer Symposium (SABCS).

As of the data cutoff date, in the intention-to-treat (ITT) population, the overall response rate (ORR) was 78.6% (95% CI, 63.2%-89.7%), and the confirmed ORR was 73.8% (95% CI, 58.0%-86.1%). Also, 1 (2.4%) patient had a complete response, 32 (76.2%) had partial responses, 7 (16.7%) reported stable disease, and 2 (4.8%) reported progressive disease. The disease control rate (DCR) in the ITT population was 95.2% (95% CI, 83.8%-99.4%).

The median progression-free survival (PFS) in the ITT population was 13.5 months (95% CI, 9.4-19.3). The 12-month overall survival (OS) rate was 80.8% (95% CI, 65.3%-89.9%), the 15-month OS rate was 78.1% (95% CI, 62.1%-88.0%), and the 18-month OS rate was 69.7% (95% CI, 52.7%-81.6%).

For patients with a PD-L1 combined positive score (CPS) of less than 1, ORR was 76.9% (95% CI, 46.2%-95.0%), DCR was 100% (95% CI, 75.3%-100%), and median PFS was 18.1 months (95% CI, 5.7-not evaluable [NE]). The 12-month, 15-month, and 18-month OS rates were all 76.9% (95% CI, 44.2%-91.9%).

For patients with a PD-L1 CPS of 1 or higher and less than 10, ORR was 68.8% (95% CI, 41.3%-89.0%), DCR was 93.8% (95% CI, 69.8%-99.8%), and median PFS was 14.0 months (95% CI, 7.2-NE). The 12-month, 15-month, and 18-month OS rates were 80.8% (95% CI, 51.4%-93.4%), 72.7% (95% CI, 42.0%-88.9%), and 64.6% (95% CI, 34.1%-83.8%), respectively.

For patients with a PD-L1 CPS of 10 or higher, ORR was 100% (95% CI, 66.4%-100%), DCR was 100% (95% CI, 66.4%-100%), and median PFS was 10.8 months (95% CI, 5.5-13.5). Additionally, 12-month, 15-month, and 18-month OS rates were 77.8% (95% CI, 36.5%-93.9%), 77.8% (95% CI, 36.5%-93.9%), and 55.6% (95% CI, 20.4%-80.5%), respectively.

“In patients with [locally advanced or metastatic TNBC], first-line therapy with PM8002/BNT327 combined with nab-paclitaxel showed clinically meaningful survival outcomes and antitumor activity regardless of PD-L1 status,” lead study author Jiong Wu, MD, PhD, of the Department of Breast Surgery at the Fudan University Shanghai Cancer Center, and fellow authors wrote in the poster. “A manageable safety profile was observed, with no new safety signals beyond those typically described for nab-paclitaxel and anti–PD-1/PD-L1 and anti-VEGF monotherapies.”

A total of 42 patients were included in the ITT population with a median age of 53.5 (IQR, 41.0-60.0). Also, 16 (38.1%) patients had liver metastasis, and 26 (61.9%) did not; 2 (4.8%) patients had brain metastasis, and 40 (95.2%) did not.

Patients received 20 mg/kg of PM8002/BNT327 every 2 weeks and 100 mg/m² of nab-paclitaxel (Abraxane) on days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.

Key eligibility criteria included an age of 18 years or more, an ECOG performance status of 0 or 1, adequate organ function, and diagnosis of locally advanced or metastatic TNBC without prior systemic therapy for unresectable locally advanced disease or metastatic advanced TNBC.

The trial’s primary end points were ORR and safety. Key secondary end points were PFS, DCR, and OS.

Regarding safety, grade 3 or higher treatment-related adverse events (TRAEs) were observed in 59.5% of patients, TRAEs leading to dose interruption occurred in 27 (64.3%) patients, dose reduction occurred in 6 (14.3%) patients, and discontinuation occurred in 4 (9.5%) patients. The most common TRAEs were neutrophil count decreases (85.7%), white blood cell count decreases (76.2%), anemia (76.2%), proteinuria (64.3%), and alopecia (57.1%).

Immune-related AEs were observed in 13 (31.0%) patients, 4 (9.5%) of which were grade 3 or higher. The most common immune-related AEs were hyperthyroidism, hypothyroidism, and rash.

Reference

Wu J, Zhang J, Tong Z, et al. Interim overall survival of patients with locally advanced or metastatic triple-negative breast cancer treated with first-line PM8002/BNT327 in combination with nab-paclitaxel in phase 1b/2 study. Presented at: 2024 San Antonio Breast Cancer Symposium; December 10-13, 2024; San Antonio, TX. Abstract PS3-08.