Innovent Biologics has announced the successful dosing of the first participant in a pivotal Phase 3 clinical trial evaluating IBI354, a novel HER2-targeted antibody-drug conjugate (ADC), for the treatment of platinum-resistant ovarian cancer (PROC) with HER2 expression.
The randomized, controlled, multicenter study, named HeriCare-Ovarian01 (NCT06834672), represents the first Phase 3 trial in China specifically investigating PROC with HER2 expression (IHC 1+, 2+, or 3+). The trial will compare IBI354 against investigator's choice of chemotherapy, with progression-free survival (PFS) and overall survival (OS) as primary endpoints.
Promising Phase 1/2 Results
Earlier Phase 1/2 data from 87 participants with platinum-resistant ovarian cancer showed encouraging results. As of July 2024, the overall objective response rate (ORR) was 40.2%, with disease control rate (DCR) reaching 81.6%. Notably, in the 40 participants receiving the 12mg/kg every three weeks (Q3W) dosing regimen, the ORR increased to 52.5% with a DCR of 90.0%.
The drug demonstrated particular efficacy in patients with low HER2 expression (IHC 1+), achieving a 55.6% ORR and 88.9% DCR in the 12mg/kg Q3W dose group. This is significant as approximately 38% of ovarian cancer patients have some level of HER2 expression, yet no anti-HER2 treatments are currently approved for HER2-expressing ovarian cancer in China.
Safety Profile
In the broader Phase 1/2 study involving 368 participants, IBI354 exhibited an excellent safety profile:
- No dose-limiting toxicities occurred up to the 18mg/kg dose level
- Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 21.5% of patients
- Only 1.6% of participants discontinued treatment due to TRAEs
- No treatment-related deaths were reported
- The most common adverse events were nausea, decreased white blood cell count, and anemia
- Interstitial lung disease, a concern with some ADCs, occurred in only 1.6% of patients and was limited to grade 1
Addressing an Urgent Unmet Need
Professor Qi Zhou from Chongqing University Cancer Hospital, the Principal Investigator of the study, emphasized the urgent need for effective treatments for PROC: "Ovarian cancer is characterized by a pattern of frequent recurrence, which ultimately leads to platinum resistance. Non-platinum monotherapy chemotherapy remains the primary treatment option at this stage, but its limited efficacy is a major contributor to the high mortality rate."
According to the International Agency for Research on Cancer, approximately 324,000 new cases of ovarian cancer were diagnosed worldwide in 2022, resulting in about 206,000 deaths. In China alone, there were approximately 61,000 new cases and 33,000 deaths reported.
About 70% of patients with initially platinum-sensitive ovarian cancer eventually develop platinum resistance. Current treatment options for these patients are limited, with objective response rates of only 4-13.2% and median overall survival of 10.9-14 months with non-platinum chemotherapy with or without anti-angiogenic therapy.
Innovative Drug Design
IBI354 is an innovative HER2-targeted antibody-drug conjugate developed using Innovent's proprietary topoisomerase inhibitor platform. The drug features:
- A drug-to-antibody ratio (DAR) of 8, delivering a high payload of effective drugs to tumors
- A highly hydrophilic linker design for excellent biophysical and pharmacokinetic properties
- A hydrophobic payload that enhances its bystander effect, targeting adjacent antigen-low or negative tumor cells
- Extremely low exposure of free toxin in circulation
Professor Tao Zhu from Zhejiang Cancer Hospital, the Principal Collaborating Investigator, noted: "Although ovarian cancer ranks third among gynecologic malignancies in incidence, behind cervical and endometrial cancers, its mortality rate exceeds the combined total of the latter two, making it the deadliest gynecologic cancer and a severe threat to women's health."
Future Development Plans
Dr. Zhou Hui, Senior Vice President of Innovent, stated that beyond the HeriCare-Ovarian01 study, Innovent plans to develop IBI354 for multiple solid tumor indications. The company considers ADC technology a core strategic area, combining "world's leading antibody engineering and multiple sets of differentiated linker-payload technologies to create a highly competitive and innovative TOPO1i ADC technology platform SoloTx®."
Innovent Biologics, founded in 2011, has already launched 15 products in the market and has 3 new drug applications under regulatory review, along with 4 assets in Phase III or pivotal clinical trials and 15 more molecules in early clinical stages.
The successful initiation of this Phase 3 trial marks an important milestone in addressing the significant unmet need for effective treatments for platinum-resistant ovarian cancer patients with HER2 expression.
