Innovent Begins Phase 3 Trial of IBI354 for Platinum-resistant Ovarian Cancer

Innovent Biologics, Inc., a renowned biopharmaceutical company based in SAN FRANCISCO and SUZHOU, China, announced the successful dosing of the first participant in a Phase 3 clinical trial involving its drug candidate, IBI354. This randomized, controlled, and multicenter study, named HeriCare-Ovarian01, focuses on treating platinum-resistant ovarian cancer (PROC) with HER2 expression and is the first of its kind in China to investigate this condition.

IBI354 is a HER2 Monoclonal Antibody-Camptothecin Derivative Conjugate (HER2 ADC) designed to combat PROC. The study aims to assess the safety and efficacy of IBI354 compared to traditional chemotherapy options chosen by investigators. Primary measures for the trial include progression-free survival (PFS) and overall survival (OS).

The development of IBI354 follows promising results from a previous multicenter Phase 1/2 study, which involved 87 participants with advanced solid tumors, including ovarian cancer. Participants received doses ranging from 6 to 12 mg/kg. Of the participants, 77% had undergone at least three previous anti-tumor treatments. As of July 2024, the overall objective response rate (ORR) stood at 40.2%, with a disease control rate (DCR) of 81.6%. Notably, a subgroup of 40 participants receiving a 12 mg/kg dose every three weeks demonstrated an ORR of 52.5% and a DCR of 90.0%. Another subgroup of 27 participants with HER2 IHC 1+ showed an ORR of 55.6% and DCR of 88.9%.

The safety profile of IBI354 is notable for its low incidence of severe treatment-related adverse events (TRAEs). In the Phase 1/2 trial, no dose-limiting toxicities occurred up to 18 mg/kg. Grade 3 or higher TRAEs were reported at 21.5%, with 12.2% leading to dose interruptions. Only 2.4% required dose reductions, and 1.6% resulted in treatment discontinuation, with no fatalities. Common TRAEs included nausea, decreased white blood cell count, and anemia, while interstitial lung disease was observed in only 1.6% of cases, all at grade 1 severity.

Prof. Qi Zhou from Chongqing University Cancer Hospital, leading the HeriCare-Ovarian01 study, emphasized the urgent need to improve survival for PROC patients, given ovarian cancer's high recurrence and resistance to platinum-based treatments. As a HER2-targeted therapy, IBI354 has demonstrated efficacy comparable to treatments for breast and gastric cancers, particularly in patients with low HER2 expression. Its excellent safety profile, characterized by minimal common ADC toxicities, makes it a promising candidate for enhancing patient outcomes.

Prof. Tao Zhu from Zhejiang Cancer Hospital, a principal collaborator in the study, highlighted the significance of IBI354 in addressing ovarian cancer's high mortality rates. Preliminary findings have shown encouraging response and disease control rates, with IBI354 exhibiting superior safety and tolerability compared to other ADCs. The promising clinical data suggest a bright future for IBI354 in treating PROC and potentially expanding treatment options for patients.

Dr. Zhou Hui, Senior Vice President at Innovent, expressed optimism for IBI354's Phase III trial outcomes, aiming to provide better treatment alternatives for patients with HER2-expressing PROC. Innovent's strategic focus on antibody-drug conjugates (ADCs) and innovative technology platforms like SoloTx® underscores their commitment to advancing cancer treatment and care.

Ovarian cancer remains a leading cause of death among gynecological cancers, with high relapse rates following platinum-based chemotherapy. Effective treatment options for platinum-resistant cases are limited, creating an urgent need for innovative therapies. Approximately 38% of ovarian cancer patients exhibit HER2 expression, yet no approved anti-HER2 treatments exist in China for this indication.

IBI354, developed using Innovent's proprietary topoisomerase inhibitor platform, features a drug-to-antibody ratio of 8, facilitating high payload delivery to tumors. Its design enhances biophysical and pharmacokinetic properties while targeting adjacent low or negative antigen tumor cells. Preclinical and clinical studies have showcased its remarkable anti-tumor activity, particularly in resistant and metastatic tumor models.

Innovent continues to explore IBI354 across multiple solid tumor indications, driven by urgent clinical needs and the promising potential shown in ongoing studies. As a leader in the biopharmaceutical industry, Innovent remains committed to developing affordable, high-quality medicines that address complex diseases and improve patient outcomes worldwide.