OncoC4 Reports 33% Response Rate with Cesalatamig in NSCLC

OncoC4 has reported encouraging Phase 1/2 results for cesalatamig (AI-081), an investigational PD-1/VEGF bispecific antibody, as monotherapy in patients with PD-(L)1-resistant or refractory non-small cell lung cancer (NSCLC). The findings, from pooled analyses of two clinical studies, showed an objective response rate (ORR) of 33% and a disease control rate (DCR) of 90% at the 10 mg/kg dose administered every three weeks (Q3W). The data will be presented as a late-breaking oral presentation at the 41st Annual Meeting of the Society for Immunotherapy of Cancer (SITC 2026) on November 7, 2026.

Clinical Results Show Increasing Antitumor Activity Across Doses

The findings come from a pooled analysis of the global BiPAVE-001 and BiPAVE-001 CN Phase 1/2 studies. As of July 31, 2026, the safety population included 103 patients with NSCLC who had received at least one dose of cesalatamig monotherapy at 1, 3, 10 or 20 mg/kg Q3W.

Among these patients, 75% had non-squamous NSCLC, 24% had squamous histology and one patient had unknown histology. The median number of prior treatment lines was two, while 42% had received at least three previous lines. Most patients (77%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 at baseline.

In the efficacy-evaluable population of 55 patients with PD-(L)1-resistant or refractory NSCLC, investigator-assessed ORR increased with dose. The response rates were 10% at 1 mg/kg, 21% at 3 mg/kg and 33% at 10 mg/kg. Corresponding DCRs were 40%, 67% and 90%, respectively.

The dose-specific efficacy populations included 10 patients at 1 mg/kg, 24 at 3 mg/kg and 21 at 10 mg/kg. At the highest dose included in this efficacy analysis, the 33% ORR represented approximately seven responders. Although the increasing response and disease control rates indicate a dose-related activity pattern, the small cohort sizes warrant cautious interpretation.

Responses were observed across different PD-L1 expression levels. Based on exposure-response analyses, OncoC4 selected 10 mg/kg Q3W for further clinical development.

Manageable Safety Profile Observed

Cesalatamig monotherapy was reported to be well tolerated across all evaluated dose levels. The company also reported comparable safety profiles between patients with squamous and non-squamous NSCLC.

These findings suggest that the observed antitumor activity was accompanied by a manageable safety profile in this previously treated population. However, the available announcement does not provide detailed adverse-event rates, including grade 3 or higher events, serious adverse events or treatment discontinuations. Further safety reporting will therefore be important to characterize the treatment’s tolerability more comprehensively.

Dual PD-1 and VEGF Targeting Provides the Therapeutic Rationale

Cesalatamig is a tetravalent bispecific antibody designed to target PD-1 and vascular endothelial growth factor (VEGF). Its mechanism aims to combine immune checkpoint inhibition with VEGF blockade within the tumour microenvironment.

PD-1 inhibition is intended to restore antitumor T-cell activity, while VEGF inhibition may help modify the immunosuppressive tumour environment. The antibody also incorporates Fc-silencing modifications designed to avoid depletion of PD-1-positive effector T cells.

This dual-targeting approach provides the biological rationale for evaluating cesalatamig in patients whose disease has progressed following PD-(L)1-targeted immunotherapy. However, the current clinical findings do not establish whether this strategy can overcome acquired immunotherapy resistance or improve outcomes compared with existing treatments.

 Clinical Development and Regulatory Outlook

Cesalatamig is being evaluated through the BiPAVE-001 programme (NCT06635785) and BiPAVE-001 CN study (CTR20253261), which investigate the antibody as monotherapy and in combination with standard-of-care treatments.

In September 2026, the US Food and Drug Administration (FDA) granted cesalatamig Fast Track designation for NSCLC that has progressed following concurrent or sequential PD-(L)1-targeted immunotherapy and platinum-based chemotherapy. The designation is intended to facilitate development and regulatory interactions for treatments addressing serious conditions with unmet medical needs. It does not represent marketing approval.

Path Forward

The selection of 10 mg/kg Q3W establishes the dose for further monotherapy development in previously treated NSCLC. OncoC4 intends to advance the programme towards a planned pivotal study, supported by the observed clinical activity and exposure-response findings.

The pooled results will be presented at SITC 2026 as late-breaking abstract #1187. Further clinical evaluation will be needed to establish the durability of responses, characterize the safety profile and determine whether cesalatamig can provide meaningful clinical benefit for patients whose NSCLC progresses after immunotherapy and chemotherapy.

Reference

OncoC4 Reports Encouraging Phase 1/2 Data for Cesalatamig Monotherapy in Previously Treated Non-Small Cell Lung Cancer at SITC 2026, OncoC4, 06 November 2026

Safety, Pharmacokinetics, and Efficacy of AI-081, a Bispecific Antibody for PD-1 And VEGF in Advanced Solid Tumors (BiPAVE-001), ClinicalTrials.gov ID NCT06635785