Frontline IMM2510 Plus Chemo Drives Responses in Advanced NSCLC

Frontline treatment with the combination of the PD-L1 x VEGF bispecific antibody IMM2510 (AXN-2510) in combination with chemotherapy produced responses in patients with advanced non–small cell lung cancer (NSCLC), according to data from a phase 2 trial (NCT06746870) being conducted in China.1

Findings demonstrated that efficacy-evaluable patients (n = 21) experienced an overall response rate (ORR) of 62%, which comprised only partial responses (PRs). These PRs were observed in 80% of patients with squamous NSCLC (n = 10) and 46% of patients with nonsquamous disease (n = 11). Notably, most evaluable patients had undergone only 1 tumor assessment at data cutoff.

Regarding safety, no dose-limiting toxicities were reported in the safety population (n = 33). Treatment-related adverse effects (TRAEs) did not lead to any dose reductions or death, and 1 patient discontinued treatment due to a TRAE. Adverse effects (AEs) were generally associated with VEGF inhibition, such as hypertension, proteinuria, hemoptysis; immune-related AEs were infrequent and mostly low-grade.

Full data from the study will be presented at a future medical meeting.

“[IMM2510] has demonstrated early but compelling activity in [patients with] frontline NSCLC,” Caicun Zhou, MD, PhD, director of the Department of Oncology at Shanghai East Hospital, Tongji University, in China, and lead investigator on the study, stated in a news release. “The PD-[L]1 x VEGF bispecific class has the potential to become the new standard of care for frontline NSCLC, and I look forward to the generation of additional data with [IMM2510] in this setting.”

Phase 2 Trial Breakdown

The single-arm, multicenter, open-label study is enrolling patients at least 18 years of age with EGFR wild-type NSCLC who do not harbor ALK or ROS1 gene fusions.2 Cohort 1a is including patients with nonsquamous NSCLC, and cohort 1b is intended for patients with squamous disease. The study also includes a cohort for patients with triple-negative breast cancer.

In the NSCLC cohorts, prior systemic therapy for advanced NSCLC is not permitted. At least 12 months must have passed for patients who received neoadjuvant or adjuvant therapy. Other key inclusion criteria comprise an ECOG performance status of 0 or 1, measurable lesions per RECIST 1.1 criteria, and an expected survival of at least 12 weeks.

Investigators are excluding patients who receive antitumor treatment within 4 weeks prior to the start of study treatment; receive nonspecific immunomodulatory treatments within 2 weeks prior to the start of the study; were previously treated with any antibody or inhibitor targeting PD-1, PD-L1, or VEGF; have a history of pulmonary fibrosis or current presence of severe pulmonary functional impairment; have uncontrolled chronic disease; have unresolved toxicity; have uncontrolled brain metastases; have active infection; or are at risk for bleeding.

In the nonsquamous cohort, patients are receiving IMM2510 at 10 mg/kg or 20 mg/kg once every 3 weeks in part 1, and 20 mg/kg once every 3 weeks in part 2. They are also receiving pemetrexed at 500 mg/m2 in combination with carboplatin at area under the curve (AUC) 5/6 or cisplatin at 75 mg/m2 once every 3 weeks 4 cycles, followed by maintenance pemetrexed. In the squamous cohort, IMM2510 is dosed at the same levels, and the chemotherapy regimen includes paclitaxel at 175 mg/m2 plus carboplatin at AUC 5/6 or cisplatin at 75 mg/m2 once every 3 weeks for 4 cycles.

Investigator-assessed ORR is the trial’s primary end point.

“We are delighted to witness the progress of [IMM2510] in frontline NSCLC. [These] data pave the way for its advancement into phase 3 clinical studies and provides valuable insights to support further research across multiple indications,” Tian Wenzhi, chief executive officer of ImmuneOnco, added in the news release.1

References

1. ImmuneOnco announced preliminary safety & efficacy data from the clinical trial studying IMM2510/AXN-2510, a PD-L1xVEGF bispecific antibody, in combination with chemotherapy in front-line NSCLC in China. News release. Instil Bio. July 31, 2025. Accessed July 31, 2025. https://ir.instilbio.com/news-releases/news-release-details/immuneonco-announced-preliminary-safety-efficacy-data-clinical
2. A phase II clinical study to evaluate the safety, pharmacokinetic profile, and preliminary efficacy of IMM2510 in combination with chemotherapy as first-line treatment in subjects with non-small cell lung cancer or triple-negative breast cancer. ClinicalTrials.gov. Updated December 24, 2024. Accessed July 31, 2025. https://clinicaltrials.gov/study/NCT06746870