On August 24, 2025 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company committed to developing, manufacturing and commercializing high-quality medicines in oncology, cardiovascular and metabolic diseases, autoimmune, ophthalmology and other major therapeutic areas, reported that the U.S. Food and Drug Administration (FDA) has cleared the investigational new drug (IND) application to initiate a global Phase 3 clinical trial (MarsLight-11) of IBI363 in immunotherapy(IO)-resistant squamous non-small cell lung cancer (NSCLC) (Press release, Innovent Biologics, AUG 24, 2025, View Source [SID1234655447]). IBI363 is Innovent’s self-discovered novel PD-1/IL-2α-bias bispecific antibody fusion protein. The upcoming study will be the first global Phase 3 trial of IBI363 and represents a significant milestone in advancing a first-in-class, dual-immune activation immunotherapy for this large patient population. Besides, the pivotal trial of IBI363 head-to-head against pembrolizumab (Keytruda) in the treatment of melanoma is underway in China.
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IBI363 as a Next-generation IO therapy Set for First Global Phase 3 Lung Cancer Trial
This IND clearance follows recent positive feedback from the U.S. FDA at the End-of-Phase 2 (EOP2) meeting. Major alignments of the Phase 3 program were reached regarding the dose selection, study design, and other critical considerations. Innovent has also received IND approval from China’s National Medical Products Administration (NMPA) for this program. In parallel, Innovent has initiated communications and submissions to other major Health authorities. IBI363 has also received Fast Track Designation (FTD) from the FDA and Breakthrough Therapy Designation (BTD) from the National Medical Products Administration (NMPA) in China for this indication.
The multi-regional, randomized, controlled Phase 3 trial will enroll approximately 600 patients globally including China, U.S., Canada, EU, UK, and Japan, etc. The study will evaluate the efficacy and safety of IBI363 3 mg/kg monotherapy compared with docetaxel in patients with unresectable, locally advanced or metastatic squamous NSCLC who have experienced disease progression following platinum-based chemotherapy and anti-PD-1/PD-L1 immunotherapy. The primary endpoint is overall survival.
IBI363’s Breakthrough Data Validates its Dual-immune Activation Mechanism, Stepwise Development in Multiple Tumor Types
At ASCO (Free ASCO Whitepaper) 2025, Phase 1b/2 results demonstrated meaningful and durable clinical activity in areas of high unmet need, including IO-resistant lung cancer, traditionally "cold tumors" such as acral and mucosal melanoma, and microsatellite stable (MSS) colorectal cancer.
These promising data position IBI363 as a potential first-in-class dual-immune activation therapy with broad applicability across difficult-to-treat cancers. Innovent is rapidly progressing IBI363 into registrational studies, with a pivotal program in melanoma already ongoing, a global Phase 3 trial in squamous NSCLC expected to start shortly, and a registration strategy in colorectal cancer in planning.
In parallel, multiple Phase 1b/2 trials are evaluating IBI363 both as monotherapy and in combinations in first-line NSCLC, first-line CRC, and additional tumor types, including platinum-resistant ovarian cancer (PROC), EGFR+ NSCLC, and neoadjuvant therapy for non-squamous NSCLC. This comprehensive development strategy is designed to maximize the value of IBI363 and expand its potential to address multiple large global oncology markets and improve patient outcomes.
Roy S. Herbst, MD, PhD, Deputy Director and Chief of Medical Oncology and Hematology for Yale Cancer Center and Smilow Cancer Hospital, Ensign Professor of Medicine (Medical Oncology) and Professor of Pharmacology at Yale School of Medicine, shared, "Lung cancer remains the most prevalent malignant tumor worldwide, with particularly high incidence and mortality rates globally. Non-small cell lung cancer constitutes the majority of these cases. 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.
Clinical research of the PD-1/IL-2α-biased bispecific molecule IBI363 has revealed encouraging findings. Preliminary trials have demonstrated that IBI363 not only induces tumor remission in a subset of patients but also achieves disease stability in the majority of patients, indicating durable anti-tumor activity. In comparison to traditional chemotherapy, IBI363 appears to offer potential advantages in both objective response rate (ORR) and progression-free survival (PFS), providing new hope for patients diagnosed with lung cancer."
Professor Shun Lu from the Oncology Department of Shanghai Chest Hospital, stated: "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. The IL-2 arm of IBI363 is engineered to retain its affinity for IL-2Rα while reducing binding to IL-2Rβ and IL-2Rγ, thereby minimizing toxicity. The PD-1 binding arm not only blocks PD-1 but also selectively delivers IL-2. 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. IBI363 has demonstrated robust antitumor activity across multiple tumor models and has shown remarkable efficacy in IO-resistant, PD-L1 low expression, and cold tumor settings.
The promising data associated with IBI363 offers a novel treatment avenue for patients with non-small cell lung cancer who have not responded to immunotherapy. As research progresses, this innovative therapy holds the potential to bridge clinical gaps and provide the possibility of long-term survival for a greater number of patients."
Dr. Hui Zhou, Chief R&D Officer for Oncology Pipeline at Innovent Biologics, said, "Today’s IND clearance marks a significant milestone as we initiate the first global Phase 3 trial of our next-generation IO therapy, IBI363 (PD-1/IL-2α-bias). If successful, this trial could bring a potentially transformative treatment to patients with squamous NSCLC worldwide, who currently have limited options after checkpoint inhibitor therapy. Concurrently, we are exploring IBI363 in a broad global clinical program and look forward to more data and continued development in the future.
This achievement also signifies a milestone for Innovent’s global innovation strategy, rooted in our mission to ’empower patients worldwide with affordable, high-quality biopharmaceuticals’ and our vision to ‘build a global premier biopharmaceutical leader.’ Having developed a highly competitive pipeline aligned with our globalization strategy, we have prioritized the global R&D of our assets, alongside expanding our international team and footprint to accelerate the development and access of innovative therapies worldwide.
In addition to IBI363, Innovent is advancing a broader pipeline for global development, including next-generation ADC programs such as bispecific and dual-payload ADCs. We believe our robust pipeline and ongoing R&D efforts will continue to expand our impact in oncology on a global scale."