Innovent Presents Phase 1 Clinical Data of First-in-class PD-1/IL-2α Bispecific Antibody Fusion Protein (IBI363) in Melanoma, Colorectal Cancer and other Solid Tumors at the 2024 ASCO Annual Meeting

SAN FRANCISCO, U.S. and SUZHOU, China, June 2, 2024 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, presented the Phase 1 clinical data of its first-in-class PD-1/IL-2^α bispecific antibody fusion protein (R&D code: IBI363) in advanced solid tumors at the 2024 ASCO Annual Meeting (ClinicalTrials.gov, NCT05460767). More updated data from the Phase 1 study including in non-small cell lung cancer will be presented orally at the European Society for Medical Oncology (ESMO) Virtual Plenary later this month.

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "We are pleased to present the Phase 1 results of IBI363 at ASCO. IL-2 is one of the earliest immunotherapies approved for cancer treatment, however, the safety and efficacy of IL-2 therapy have not been satisfactory. IBI363, a novel PD-1/IL-2 bispecific molecule, designed to selectively activates PD-1 and CD25 positive T cells by cis-activating IL-2, with the potential to significantly decrease toxicity related to IL-2 and potentially overcome immunotherapy resistance. We are excited that in the Phase 1 study, IBI363 achieved unprecedented dosing levels, overcoming safety concerns associated with IL-2 therapy. Meanwhile, as IBI363 monotherapy has already shown efficacy signals and good tolerability in IO failed melanoma (most patients with mucosal or acral subtypes) and non-small cell lung cancer, cold tumors such as colorectal cancer and several other tumor types. These results suggest the broad-spectrum anti-tumor effect of IBI363. This study is ongoing to further explore the long-term benefits and the potential optimal dose of IBI363. As immunotherapy moves into the next era, we are actively advancing the development of next-generation immune medicines, and hope to benefit more patients in need." 

Phase 1 Study of PD-1/IL-2^α (IBI363) in Melanoma, Colorectal Cancer and Other Solid Tumors

This Phase 1a/1b study was conducted to evaluate the safety, tolerability and preliminary efficacy of IBI363 in subjects with advanced solid tumors.

For melanoma cohort (abstract#: 9562): 

• 67 subjects with locally advanced or metastatic melanoma who failed or intolerant to standard treatment were enrolled and received IBI363 intravenously at dose levels between 100 μg/kg QW and 2 mg/kg Q3W. 89.6% of subjects had received prior immunotherapy, and 61.2% of subjects had ≥ 2 lines of prior systemic therapy. 25.4% of subjects had baseline liver metastasis and 70.1% of subjects were acral or mucosal subtypes.
  
  
• As of Jan 11, 2024, 57 subjects had at least 1 post-baseline tumor assessment. The best overall response was complete response (CR) in 1 subject, partial response (PR) in 15 subjects respectively. The overall response rate (ORR) was 28.1% (95%CI: 17.0-41.5) and DCR was 71.9% (95%CI: 58.5-83.0). In 25 immunotherapy (IO) treated subjects in 1mg/kg Q2W dose group (n=25), the ORR was 32.0% (95%CI: 14.9-53.5), DCR was 80.0% (95%CI: 59.3-93.2).
  
  
• As for safety, 16 (23.9%) subjects had grade ≥3 treatment emergent adverse events (TEAEs). Most common TEAEs were arthralgia (34.3%), hyperthyroidism (29.9%), and anemia (25.4%). Grade ≥3 immune related adverse events (irAEs) occurred in 8 (11.9%) subjects. No TRAE leading to death occurred.

For colorectal cancer cohort (abstract#: 3593):

• 68 subjects with locally advanced or metastatic colorectal cancer who failed or intolerant to standard treatment were enrolled and received IBI363 intravenously at dose levels between 100 μg/kg QW and 3 mg/kg Q3W. There were 83.8% subjects with microsatellite stable (MSS)/proficient mismatch repair (pMMR), and the MMR status of the others were unknown. 76.5% of the subjects had previously received ≥ 3rd line system therapy, and 61.8% of subjects had liver metastases at baseline.
  
  
• As of Dec 22, 2023, median follow-up time was 5.3 (95% CI: 4.4-6.9) months. The best overall response was complete response (CR) in 1 subject, partial response (PR) in 7 subjects respectively. The overall ORR was 12.7% (95%CI: 5.6-23.5). The ORR of the 1 mg/kg dose group was 15.0% (95% CI: 3.2-37.9). In 13 subjects with PD-L1 CPS ≥1, ORR was 30.8% (95%CI: 9.1-61.4), DCR was 76.9% (95%CI: 46.2-95.0).
  
  
• As for safety, grade ≥3 treatment emergent adverse events (TEAEs) occurred in 22 (32.4%) subjects. Most common TEAEs were arthralgia (35.3%), anemia (32.4%), pyrexia (22.1%) and hypoalbuminemia (20.6%). Grade ≥3 immune related adverse events (irAEs) occurred in 4 (5.9%) subjects. No TRAE leading to death occurred.

For other tumors (abstract#:e14593):

• As of January 26, 2024, 13 subjects with biliary tract cancers (BTC), 3 subjects with head and neck squamous cell carcinoma (HNSCC), 4 subjects with cervical cancer (CC) and 4 subjects with ovarian cancer (OC) received IBI363 monotherapy.
  
  
• In 11 evaluable patients with BTC, 1 patient (IO-failed) had confirmed partial response (cPR), 9 patients (including 6 patients with tumor regression) had stable disease (SD) and 1 patient  had progressive disease (PD). In 2 evaluable patients with HNSCC, 1 patient had cPR (IO-naïve, PD-L1 expression negative) and 1 patient had PD. In 3 evaluable patients with CC, 1 patient had cPR (IO-failed), 1 patient had SD and 1 patient had PD. In 2 evaluable patients with OC, 1 patient had cPR (platinum-resistant) and 1 patient had PD. In 4 patients with cPR, 3 patients still on treatment and 1 patient with HNSCC received curative resection.

Professor Yu Chen, Fujian Cancer Hospital, stated: "Melanoma is a rare tumor type in China, and the majority of patients are acral or mucosal subtypes, which are not sensitive to immunotherapy (about 60%-70%). IL-2, as an important cytokine that activates tumor-specific CD8+T cells and mechanistically complementary to immune checkpoint inhibitors, has long become a well-established target in melanoma. As a novel PD-1/IL-2^α bispecific molecule, IBI363 demonstrate significantly higher response rate compared to the current standard of care in IO failed melanoma, and the response is durable. IBI363 is well tolerated, and the toxicity is manageable. The current safety profile is similar to that of previous PD-1 monoclonal antibodies. The clinical data suggests that IBI363 has great development potential in melanoma population. Clinical trials are ongoing for further confirming the clinical benefits of IBI363 in melanoma population."

Professor Tingbo Liang, The First Affiliated Hospital, School of Medicine, Zhejiang University, stated: "CRC is the third most common diagnosed cancer and the second leading cause of cancer death[1]. 50%~60% of patients diagnosed with CRC develop distant metastases during their disease course, and the prognosis of metastatic CRC is poor, with a 5-year survival rate of less than 20%[2].  For subjects with advanced CRC who have failed standard chemotherapy, the ORR for existing treatments is only 1% ~ 4.7%, and the median overall survival is only 6 ~ 9 months[3]. Promising efficacy of IBI363 was observed in subjects with advanced CRC, particularly in subjects with PD-L1 CPS ≥1, with a manageable safety profile. We are looking forward to the study of IBI363 monotherapy or combination therapy in advanced CRC and hope to bring new treatment options to more patients."

About IBI363 (PD-1/IL-2^α)

IBI363 is a first-in-class drug candidate independently developed by Innovent Biologics. Its active ingredient is PD-1/IL-2 bispecific antibody fusion protein. The IL-2 arm of IBI363 has been engineered to maximize efficacy and reduce toxicity, whereas the PD-1 binding arm achieves PD-1 blockade and selective IL-2 delivery. Therefore, IBI363 has both functions of simultaneously blocking PD-1/PD-L1 pathway and activating IL-2 pathway, allowing more precise and efficient targeting and activation of tumor specific T cells. IBI363 not only showed promising anti-tumor activity in a variety of tumor-bearing pharmacological models, but also exhibited prominent antitumor efficacy in PD-1 resistant and metastatic models; meanwhile, IBI363 demonstrated a good safety profile in preclinical models. Currently, clinical studies of IBI363 are conducted in China, United States, and Australia to assess the safety, tolerability, and preliminary efficacy in subjects with advanced malignancies.

About Innovent Biologics:

Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 10 products in the market. It has 4 new drug applications under regulatory review, 4 assets in Phase III or pivotal clinical trials and 18 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Sanofi, Incyte, Adimab, LG Chem and MD Anderson Cancer Center.

Guided by the motto, 'Start with Integrity, Succeed through Action,' Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.

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