FDA Grants Fast Track Designation to Cesalatamig in Immunotherapy-Pretreated NSCLC

The FDA has granted fast track designation to cesalatamig (AI-081) as a potential therapeutic option for patients with non–small cell lung cancer (NSCLC) whose disease has progressed following concurrent or sequential PD-(L)1–targeted immunotherapy and platinum-based chemotherapy.¹

The designation was supported by clinical safety and efficacy signals observed in the ongoing global phase 1/2 BiPAVE-001 program, which comprises the United States (US)–based BiPAVE-001 study (NCT06635785) and the China-based phase 1/2 BiPAVE-001 study (CTR20253261).^1,2

“This designation reflects the clinical safety and efficacy signals we have seen in our global phase 1/2 trials, BiPAVE-001 US and BiPAVE-001 China. We are rapidly advancing to registrational phase 3 development in PD-[L]1-refractory or resistant NSCLC and other indications,” Yang Liu, cofounder, chief executive officer, and chief scientific officer of OncoC4, stated in a news release.

Fast track designation is intended to facilitate development and expedite review of agents that treat serious conditions and address an unmet medical need. It enables more frequent interaction with the FDA, eligibility for rolling review of a future application, and eligibility for priority review if relevant criteria are met.

What is the mechanism of action of cesalatamig?

Cesalatamig is a bispecific antibody that simultaneously targets PD-1 and VEGF. According to OncoC4, the agent binds PD-1 with high affinity and demonstrates more than 40-fold higher affinity for VEGF than bevacizumab-based bispecific PD-(L)1/VEGF inhibitors. The company reported that cesalatamig exhibits stronger cooperative binding in microenvironments enriched for PD-1 and VEGF, and that it incorporates Fc-silencing modifications designed to avoid depletion of PD-1–positive effector T cells.¹ Cesalatamig is one of several PD-1/VEGF bispecific antibodies under clinical investigation in NSCLC.³

How was the US-based phase 1/2 BiPAVE-001 trial designed?

The US-based BiPAVE-001 trial is a first-in-human, phase 1/2 study evaluating the safety, pharmacokinetics, and efficacy of cesalatamig in patients with advanced solid tumors.² The trial is enrolling adult patients at least 18 years of age with histologically or cytologically confirmed, metastatic or locally advanced solid tumors who have measurable disease per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, and adequate organ function.

Patients with brain or leptomeningeal metastases, uncontrolled hypertension, or a history of interstitial lung disease are among those excluded. Patients cannot be enrolled in any other clinical trials testing agents or devices, and concurrent anticancer treatment is not permitted, except for palliative bone-directed radiotherapy. Other key exclusion criteria comprise clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring frequent drainage; or a history of interstitial lung disease, non-infectious pneumonitis, or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, or acute lung disease.

The study is structured in two integrated parts.^1,2 Part A is a dose-escalation phase designed to determine the recommended phase 2 dose (RP2D) of cesalatamig monotherapy, and Part B is a dose-optimization phase comparing the RP2D with one dose level below the RP2D (RP2D-1), administered as monotherapy or in combination with standard-of-care therapy in selected indications.¹ Cesalatamig is administered as an intravenous infusion given once every 3 weeks.²

The primary end points are the maximum tolerated dose and the incidence of dose-limiting toxicities; secondary end points include pharmacokinetic measures such as maximum serum concentration and serum half-life. The study aims to enroll approximately 387 patients, began in March 2025, and has an estimated primary completion date of June 2027.

References

1. OncoC4 receives FDA fast track designation for cesalatamig, an investigational PD-1/VEGF bispecific antibody. News release. OncoC4, Inc. September 16, 2026. Accessed September 16, 2026. https://oncoc4.com/en/news-resources/news/oncoc4-receives-fda-fast-track-designation-for-cesalatamig-an-investigational-pd-1vegf-bispecific-antibody/
2. Safety, pharmacokinetics, and efficacy of AI-081, a bispecific antibody for PD-1 and VEGF in advanced solid tumors (BiPAVE-001). ClinicalTrials.gov. Accessed September 16, 2026. https://clinicaltrials.gov/study/NCT06635785
3. RC148 Plus Chemotherapy in Frontline NSCLC: A Q&A With Yuanyuan Zhao, MD. OncLive. Published September 15, 2026. Accessed September 16, 2026. https://www.onclive.com/view/rc148-plus-chemotherapy-in-frontline-nsclc-a-q-a-with-yuanyuan-zhao-md