BioInvent International AB announced the initiation of a Phase 2a clinical trial evaluating BI-1206 in combination with Merck's anti-PD-1 therapy pembrolizumab (KEYTRUDA®) in patients with advanced or metastatic non-small cell lung cancer (NSCLC) and uveal melanoma in the first-line setting. The Swedish biotech company's decision follows encouraging Phase 1 results presented at ASCO 2024.
Phase 1 Results Drive Advancement
The Phase 1 dose escalation study demonstrated that BI-1206 was safe and well-tolerated while showing promising clinical activity in heavily pre-treated patients. Among 36 evaluable patients who had all progressed after previous treatments with anti-PD1/L1 agents, the combination achieved one complete response (CR), one long-lasting partial response (PR), and 11 patients with stable disease (SD).
Notably, one patient with long-lasting metastatic melanoma who had previously progressed on nivolumab treatment maintained stable disease throughout the entire two-year study duration with BI-1206 and pembrolizumab. The subcutaneous formulation provided slower systemic entry and prolonged time on target while improving safety and tolerability.
Phase 2a Trial Design and Timeline
The Phase 2a trial (NCT04219254) will evaluate the safety and efficacy of BI-1206 in combination with pembrolizumab across multiple international sites in Georgia, Germany, Poland, Romania, Spain, Sweden, and the United States. First data is expected in the second half of 2026.
The study will be conducted in two distinct phases. In the signal-seeking phase, up to 30 NSCLC patients and 12 uveal melanoma patients will receive BI-1206 and pembrolizumab every 21 days for up to two years. Following this initial phase, the study will proceed to a dose optimization phase designed to refine the dosing strategy to maximize both efficacy and tolerability of the combination. During dose optimization, patients will be randomized to receive either a higher or lower dose of BI-1206, while a third cohort will receive pembrolizumab alone.
Addressing Unmet Medical Needs
NSCLC represents the most common type of lung cancer, accounting for approximately 85 percent of all lung cancer cases. While checkpoint inhibitors are widely accepted and can produce durable responses in NSCLC, the overall response rate remains low, rarely exceeding 25 percent.
Uveal melanoma presents an even greater challenge as a rare and difficult-to-treat cancer, though it is the most frequent non-cutaneous melanoma and primary malignancy of the eye in adults. Globally, approximately 7,000 new cases of uveal melanoma are diagnosed annually.
Mechanism of Action
BI-1206 targets a common resistance mechanism in cancer involving the binding and degradation of therapeutic antibodies against PD-1, such as pembrolizumab, by FcγRIIB expressing immune cells. Based on preclinical and early clinical data, BioInvent believes that resistance or lack of response to anti-PD-1 treatment may be overcome by FcγRIIB blockade, particularly in subjects who have never been exposed to anti-PD-1 agents.
"We are very pleased to initiate Phase 2a studies, which marks a significant milestone in our mission to bring BI-1206 to patients," said Martin Welschof, Chief Executive Officer of BioInvent. "The early clinical signs of efficacy observed in the Phase 1 trial provide a strong rationale for moving forward in the first line setting in NSCLC and uveal melanoma, two areas of important medical need. Since BI-1206 addresses a mechanism of resistance to anti-PD1, the potential of BI-1206 extends to all indications where pembrolizumab is approved."
About BI-1206
BI-1206 is one of BioInvent's lead drug candidates, developed to re-establish the clinical effect of existing cancer treatments such as pembrolizumab and rituximab. The drug candidate is being evaluated in two separate clinical programs: one for the treatment of solid tumors and another for the treatment of non-Hodgkin's lymphoma.
