FDA Clears IND for IBI363 in Squamous Non–Small Cell Lung Cancer

"Although immunotherapy has significantly improved survival outcomes for some patients, those who do not respond to such treatments and lack driver gene mutations have limited therapeutic options, underscoring the urgent need for enhanced clinical interventions," according to Roy S. Herbst, MD, PhD.

The FDA has cleared an investigational new drug (IND) application for IBI363, a novel PD-1/IL-^2α-bias bispecific antibody, as a treatment for those with squamous non–small cell lung cancer (NSCLC) demonstrating resistance to prior immunotherapy, according to a press release from the developer, Innovent Biologics.¹

Based on the agency’s clearance, developers may now initiate the phase 3 MarsLight-11 trial of IBI363 in this NSCLC population. Acceptance of the IND followed positive feedback from an End-of-Phase 2 meeting in which the FDA and developers aligned on the dose selection, study design, and other key considerations for the phase 3 program.

The phase 3 trial will include approximately 600 patients across the US, China, Canada, EU, UK, Japan, and other areas. Investigators of the trial will assess the safety and efficacy of IBI363 at a dose of 3 mg/kg vs docetaxel among patients with unresectable, locally advanced or metastatic NSCLC after disease progression on prior platinum-containing chemotherapy and anti–PD-1 or anti–PD-L1 immunotherapy. The trial’s primary end point will be overall survival (OS).

“Lung cancer remains the most prevalent malignant tumor worldwide, with particularly high incidence and mortality rates globally. [NSCLC] constitutes the majority of these cases,” Roy S. Herbst, MD, PhD, deputy director and chief of Medical Oncology and Hematology for Yale Cancer Center and Smilow Cancer Hospital, and Ensign Professor of Medicine in Medical Oncology and professor of Pharmacology at Yale School of Medicine, said in the press release.¹ “Although immunotherapy has significantly improved survival outcomes for some patients, those who do not respond to such treatments and lack driver gene mutations have limited therapeutic options, underscoring the urgent need for enhanced clinical interventions.”

Investigators previously presented findings from a phase 1 study (NCT05460767) evaluating IBI363 monotherapy in patients with immunotherapy-resistant advanced NSCLC at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.² As of the data cutoff of April 7, 2025, the trial population consisted of 136 patients who received IBI363 from approximately 2 mg/kg every week to 4 mg/kg every 3 weeks, which included 67 patients with squamous cell carcinoma and 58 with EGFR wild-type adenocarcinoma.

Among patients who received the agent at 1 or 1.5 mg/kg every 2 weeks (n = 28) or 3 mg/kg every 3 weeks (n = 31) in the squamous NSCLC cohort, the confirmed objective response rate (ORR) was 25.9% (95% CI, 11.1%-46.3%) and 36.7% (95% CI, 19.9%-56.1%), respectively. In each respective group, the disease control rate (DCR) was 66.7% (95% CI, 46.0%-83.5%) and 90.0% (95% CI, 73.5%-97.9%), the median progression-free survival (PFS) was 5.5 months (95% CI, 1.5-8.3) and 9.3 months (95% CI, 6.2-11.7), and the median OS was 15.3 months (95% CI, 7.6-not calculable [NC]) and NC (95% CI, 10.4-NC).

Among those with EGFR wild-type adenocarcinoma who received IBI363 at 0.6 mg/kg every 2 weeks and 1 or 1.5 mg/kg every 3 weeks (n = 30) or 3 mg/kg every 3 weeks (n = 25), the confirmed ORR was 13.8% (95% CI, 3.9%-31.7%) and 24.0% (95% CI, 9.4%-45.1%), respectively, and the DCR was 62.1% (95% CI, 42.3%-79.3%) and 76.0% (95% CI, 54.9%-90.6%). Additionally, the median PFS was 2.7 months (95% CI, 1.4-5.1) and 5.6 months (95% CI, 3.1-9.4) in each respective group, and the median OS was 17.5 months (95% CI, 5.6-NC) and NC (95% CI, 9.4-NC).

According to the press release, the FDA previously granted fast track designation to IBI363 as a treatment for patients with squamous NSCLC. Furthermore, China’s National Medical Products Administration granted breakthrough therapy designation to IBI363 for the same indication.

“As a first-in-class PD-1/IL-^2α-biased bispecific antibody fusion protein, IBI363 acts by simultaneously blocking the PD-1/PD-L1 pathway and activating the IL-2 pathway…. This dual mechanism targets and activates tumor-specific T cells co-expressing PD-1 and IL-2α, enabling more precise and effective stimulation of this T-cell subpopulation,” Shun Lu, a professor from the Oncology Department of Shanghai Chest Hospital, added in the press release.¹ “IBI363 has demonstrated robust antitumor activity across multiple tumor models and has shown remarkable efficacy in [immunotherapy]-resistant, PD-L1 low expression, and cold tumor settings.”

References

1. Innovent Biologics announces U.S. FDA IND approval for the first global MRCT phase 3 study (MarsLight-11) of IBI363 (PD-1/IL-2α-bias) in squamous non-small cell lung cancer. News release. Innovent Biologics. August 24, 2025. Accessed August 25, 2025. https://tinyurl.com/3hyctz45
2. 2025 ASCO oral presentation: Innovent Biologics announces updated data of IBI363 (first-in-class PD-1/IL-2α-bias bispecific antibody fusion protein) from the phase 1 PoC clinical study in advanced non-small cell lung cancer. News release. Innovent Biologics. June 4, 2025. Accessed August 25, 2025. https://tinyurl.com/yc6e3zr2