Positioning PD-L1/VEGF Bispecifics in First-Line Non–Small Cell Lung Cancer: With Solange Peters, MD, PhD

Welcome to OncLive On Air®! I'm your host today, Caroline Seymour.

OncLive On Air is a podcast from OncLive®, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

In today's episode, we spoke with Solange Peters, MD, PhD. Dr Peters is a full professor, and chair of medical oncology and the thoracic malignancies programme in the Department of Oncology at the University Hospital of Lausanne in Switzerland.

In our exclusive interview, Dr Peters discussed the rationale for pairing antiangiogenic activity with checkpoint inhibition upfront in non–small cell lung cancer (NSCLC), rather than sequencing them. She noted that prior attempts to combine or sequence bevacizumab (Avastin) with checkpoint inhibitors yielded only modest signals, hampered by bevacizumab’s long half-life and class-specific toxicities including bleeding risk that historically excluded patients with squamous cell carcinoma. By contrast, PD-L1/VEGF bispecifics such as pumitamig carry a significantly shorter half-life of approximately 5 to 6 days, resulting in a similar toxicity category but with lower rates of high-grade events and a broadened eligible population.

She highlighted the mechanistic rationale for this combination, explaining that VEGF and PD-L1 co-targeting appears to remodel the tumor microenvironment cooperatively, bringing cancer cells into closer proximity with T cells. In the case of PD-L1/VEGF bispecifics, a macromolecular structure forms in the tumor microenvironment that leads to internalization of PD-L1, creating a dual blockade of the PD-1/PD-L1 pathway beyond simple receptor occupancy.

Dr Peters then discussed data presented at the 2026 ASCO Annual Meeting from the phase 2/3 ROSETTA Lung-02 trial (NCT06712316) evaluating pumitamig plus chemotherapy in the first-line setting. She described the activity observed across all PD-L1 expression strata, including in PD-L1–negative patients, who comprised up to 70% of the nonsquamous population and achieved response rates above 50% as particularly compelling. She also addressed the dose selection rationale, noting that the 1500-mg dose demonstrated the optimal pharmacodynamic activity and favorable risk-benefit profile for phase 3 advancement.

Finally, Dr Peters offered broader perspective on the increasingly competitive PD-L1/VEGF bispecific landscape, including the parallel development of ivonescimab. She suggested that differences in clinical trial design including patient population, inclusion and exclusion criteria, and end point ambition may ultimately differentiate agents more than mechanism alone, and emphasized that global data will be essential to shaping regulatory and clinical practice decisions.

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