Cesalatamig Monotherapy Yields Responses in PD-(L)1–Resistant NSCLC

Monotherapy with cesalatamig (AI-081), an investigational PD-1/VEGF bispecific antibody, demonstrated dose-dependent antitumor activity with a manageable safety profile in patients with PD-(L)1–resistant/refractory non–small cell lung cancer (NSCLC), according to pooled phase 1/2 results from the BiPAVE-001 program (NCT06635785) that OncoC4 will present at the Society for Immunotherapy of Cancer (SITC) 2026 Annual Meeting.^1,2

What were the efficacy outcomes?

Among 55 efficacy-evaluable patients with PD-(L)1–resistant/refractory NSCLC, cesalatamig monotherapy demonstrated dose-dependent activity across the 1-, 3-, and 10-mg/kg every-3-weeks dose levels. At 1 mg/kg (n = 10), 3 mg/kg (n = 24), and 10 mg/kg (n = 21), the investigator-assessed overall response rates (ORRs) were 10%, 21%, and 33%, respectively, and the disease control rates (DCRs) were 40%, 67%, and 90%, respectively. Responses were observed across PD-L1 expression levels, and exposure-response analyses supported selection of the 10-mg/kg every-3-weeks dose for further development.

What was the safety profile?

As of the July 31, 2026, data cutoff, the safety population included 103 patients with NSCLC who had received at least 1 dose of cesalatamig monotherapy at 1, 3, 10, or 20 mg/kg every 3 weeks. According to the developers, cesalatamig monotherapy was well tolerated at all dose levels, with a safety profile that was comparable between patients with squamous and nonsquamous histology.

In the safety population, 75% of patients had nonsquamous histology, 24% had squamous histology, and 77% had a baseline ECOG performance status of 1. The median number of prior lines of therapy was 2, and 42% of patients had received 3 or more prior lines.

“Patients whose NSCLC progresses after immunotherapy and chemotherapy have limited effective treatment options,” said Kai He, MD, PhD, principal investigator of the US BiPAVE-001 trial and the presenter of the study, in a news release.¹ “The responses and disease control observed with cesalatamig monotherapy are encouraging. Together with the manageable safety profile observed in these studies, these findings support further clinical evaluation in this setting.”

What is the trial design and mechanism?

The findings were derived from a pooled analysis of the global, multicenter, open-label BiPAVE-001 (NCT06635785) and BiPAVE-001 CN (CTR20253261) phase 1/2 studies, which are evaluating the safety, pharmacokinetics, and efficacy of cesalatamig in patients with advanced solid tumors in the US and China, respectively.³ Part A is the first-in-human phase 1 dose-escalation and dose-expansion portion, and part B is the phase 2 portion, which includes dose-optimization studies of cesalatamig as monotherapy or in combination with standard of care.

Cesalatamig is a tetravalent PD-1/VEGF bispecific antibody designed to promote cooperative PD-1 and VEGF blockade in the tumor microenvironment, combining high-affinity binding with Fc-silencing modifications intended to avoid depletion of PD-1–positive effector T cells.

What are the next steps?

Based on the clinical and exposure-response data, OncoC4 selected the 10-mg/kg every-3-weeks dose for a planned pivotal study. In September 2026, the FDA granted cesalatamig fast track designation for NSCLC that has progressed after concurrent or sequential PD-(L)1–targeted immunotherapy and platinum-based chemotherapy.⁴ The full results will be presented in a late-breaking oral presentation (Abstract 1187) at the SITC Annual Meeting in Phoenix, Arizona.

“These findings strengthen the rationale for advancing cesalatamig monotherapy in previously treated NSCLC. The clinical results and exposure-response analyses support the selection of 10 mg/kg every [3] weeks as the dose for our planned pivotal study and provide a clear path forward for the continued development of cesalatamig in this setting,” Yang Liu, PhD, co-founder, chief executive officer and chief scientific officer of OncoC4, concluded.¹

References

1. OncoC4 reports encouraging phase 1/2 data for cesalatamig monotherapy in previously treated non-small cell lung cancer at SITC 2026. News release. OncoC4 Inc. November 6, 2026. Accessed November 9, 2026. https://tinyurl.com/vmk8t6cp
2. He K, Yang J, Li M, et al. Safety and efficacy of cesalatamig, a novel PD-1/VEGF bispecific antibody, as monotherapy in PD-(L)1–resistant/refractory NSCLC: results from global, multicenter, open-label phase 1/2 studies. Presented at: 41st Annual Meeting of the Society for Immunotherapy of Cancer; November 4-8, 2026; Phoenix, AZ. Abstract 1187.
3. Safety, pharmacokinetics, and efficacy of AI-081, a bispecific antibody for PD-1 and VEGF in advanced solid tumors (BiPAVE-001). ClinicalTrials.gov. Updated August 17, 2026. Accessed November 9, 2026. https://tinyurl.com/u4ks2e3k
4. OncoC4 receives FDA fast track designation for cesalatamig, an investigational PD-1/VEGF bispecific antibody. News release. OncoC4 Inc. September 16, 2026. Accessed November 9, 2026. https://tinyurl.com/3x66zm6a