Clinical Summary:

• Design/Population: Researchers evaluated data from two randomized, open-label, phase 2 trials of pumitamig, an investigational PD-L1/VEGF-A bispecific antibody, plus chemotherapy in patients with small cell lung cancer (SCLC) or triple-negative breast cancer (TNBC), including patients with baseline brain metastases.
• Key Outcomes: Confirmed intracranial objective response rates were 38.2% in evaluable patients with SCLC and 42.9% in those with TNBC. Systemic efficacy was generally comparable between patietns with and without brain metastases, with confirmed intracranial responses observed in both cancer populations. 
• Clinical Relevance: These findings support further evaluation of pumitamig plus chemotherapy for patients with SCLC or TNBC and brain metastases, suggesting potential intracranial activity while highlighting the need for larger studies to establish the durability and clinical significance of these responses. 

Results from an analysis of two phase 2 trials demonstrated encouraging intracranial antitumor activity with pumitamig plus chemotherapy in patients with small cell lung cancer (SCLC) and triple-negative breast cancer (TNBC) with brain metastases, with generally comparable systemic efficacy regardless of baseline brain metastasis status. 

These findings were presented by Kevin Franks, MD, Leeds Cancer Centre, Leeds, England, at the European Society for Medical Oncology (ESMO) Congress. 

In this analysis, researchers collected data from two open-label, phase 2 trials enrolling patients with SCLC (n = 107) and TNBC (n = 81) to receive 1 of 2 doses of pumitamig plus chemotherapy. Baseline brain metastases were present in 37 patients in the SCLC cohort and 7 patients in the TNBC cohort. 

Systemic efficacy was evaluated according to investigator-assessed objective response rate (ORR) using RECIST version 1.1 and progression-free survival (PFS) in patients with and without baseline brain metastases.

Intracranial responses were assessed by an independent radiologist according to Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria among patients with at least 1 baseline brain lesion and at least 2 brain imaging assessments.

Among 34 intracranial response-evaluable patients with SCLC, the unconfirmed intracranial ORR was 50%, and the confirmed intracranial ORR was 38.2%. Confirmed intracranial complete responses occurred in 17.7% of patients. 

Among 7 intracranial response-evaluable patients with TNBC, both the unconfirmed and confirmed intracranial ORRs were 42.9%, with confirmed intracranial complete responses occurring in 14.3% of patients. 

Systemic antitumor activity was generally comparable between patients with and without baseline brain metastases across the evaluated treatment cohorts.

In the first-line SCLC cohort receiving pumitamig plus carboplatin and etoposide, the confirmed systemic ORR was 77.8% in patients with brain metastases and 75.9% in patients without brain metastases. 

In the second- or third-line SCLC cohort receiving pumitamig plus paclitaxel, the confirmed systemic ORR was 33.3% in patients with brain metastases and 44.4% in patients without brain metastases. Among patients receiving pumitamig plus topotecan in the second- or third-line SCLC setting, the confirmed systemic ORR was 38.5% in patients with brain metastases and 26.7% in patients without brain metastases. 

In the TNBC trial, patients received pumitamig in combination with nab-paclitaxel, paclitaxel, gemcitabine plus carboplatin, or eribulin in the first- or second-line setting. The confirmed systemic ORR was 57.1% in patients with brain metastases and 57.4% in patients without brain metastases. 

Median PFS in the TNBC cohort was 7.2 months in patients with brain metastases and 11 months in patients without brain metastases. The corresponding 6-month PFS rates were 57.1% and 67.5%, respectively. 

These findings suggest that pumitamig plus chemotherapy demonstrated systemic antitumor activity in patients with SCLC and TNBC regardless of baseline brain metastasis status, alongside encouraging intracranial responses in evaluable patients with brain lesions.

Investigators concluded that systemic efficacy with pumitamig plus chemotherapy was generally consistent between patients with and without brain metastases, while the observed intracranial responses support further investigation of the combination in patients with brain metastases.

Source:

Pavlakis N, Cho BC, Sezer A, et al. Efficacy of pumitamig (PD-L1 × VEGF-A bsAb) plus chemotherapy in patients with SCLC or TNBC with brain metastases: A subgroup analysis of two phase 2 trials. Presented at ESMO Congress. October 23–27, 2026; Madrid, Spain. Abstract 1951RO.