PrECOG PrE0510 - Phase 2 Study of Platinum-Etoposide Plus Ivonescimab for Extensive-Stage Small Cell Lung Cancer

Small cell lung cancer (SCLC) accounts for about 15% of lung cancer cases. It is highly aggressive, fast-growing, and associated with poor outcomes. Most patients already have metastatic disease at diagnosis. The standard treatment for extensive-stage SCLC consists of platinum-etoposide chemotherapy combined with PD-L1 immunotherapy, followed by maintenance immunotherapy. This regimen can improve symptoms and temporarily prolong survival by shrinking tumors and slowing progression; however, relapses are common after chemoimmunotherapy, and long-term survival is rare, with a 5-year survival rate of just 4%.

Recent studies suggest that adding a VEGF-driven angiogenesis inhibitor to the usual treatment regimen may enhance efficacy and improve outcomes. Ivonescimab is a novel bispecific antibody in clinical development designed to simultaneously target two oncologic pathways: PD-1-mediated immune checkpoint signaling and VEGF-driven angiogenesis. Because dual inhibition of PD-1 and VEGF has shown promise across multiple tumor types, a bispecific antibody that blocks both pathways may provide a single-agent approach that inhibits tumor growth through complementary mechanisms and helps reprogram the immunosuppressive tumor microenvironment into a more immune-responsive state. An early study conducted in China demonstrated promising efficacy and a favorable safety profile for ivonescimab when combined with carboplatin and etoposide chemotherapy in patients with extensive-stage SCLC.

The phase 2 PrE0510 clinical trial is designed to determine the optimal dose of ivonescimab in combination with carboplatin and etoposide chemotherapy for a more diverse Western patient population. The enrollment goal is 60 patients in the United States, and eligible participants will be stratified by ECOG performance status (0 vs. 1) and presence of brain metastases (yes/no), and then randomized 1:1 to receive:

• Ivonescimab 10 mg/kg IV and chemotherapy, followed by maintenance ivonescimab 10 mg/kg IV every 21 days; or
• Ivonescimab 20 mg/kg IV and chemotherapy, followed by maintenance ivonescimab 20 mg/kg IV every 21 days

Patients will continue maintenance therapy until disease progression or unacceptable toxicity. All patients will be followed for up to 3 years after finishing study treatment.

To be eligible for the study, patients must have pathologically confirmed extensive-stage SCLC. They must not have received prior systemic therapy for their disease and must have measurable disease according to Response Evaluation Criteria for Solid Tumors v1.1.

Given that outcomes for patients with extensive-stage SCLC remain poor, there is a clear need for well-designed frontline studies that can be efficiently conducted in routine oncology practice. This trial builds on encouraging early data and uses a familiar chemotherapy backbone, making it feasible for sites to activate quickly and enroll appropriate patients while contributing to an important dose-selection effort.

Learn more about PrE0510 at clinicaltrials.gov.

The study chair for this trial is Taofeek K. Owonikoko, MD, PhD (University of Maryland/Marlene and Stewart Greenebaum Comprehensive Cancer Center). The co-chair is Nisha A. Mohindra, MD (Northwestern University/Robert H. Lurie Comprehensive Cancer Center).