The first patient has been successfully dosed with IBI354 in the phase 3 clinical trial HeriCare-Ovarian01 for patients with platinum-resistant ovarian cancer and HER2 expression, according to the drug’s manufacturer, Innovent Biologics, Inc.
"Prolonging [progression-free survival] and [overall survival] of [platinum-resistant ovarian cancer] is an urgent unmet medical need,” professor Qi Zhou of Chongquing University Cancer Hospital in China, said in the news release.
Zhou explained that ovarian cancer is marked by frequent recurrence, ultimately leading to platinum resistance. At this stage, non-platinum monotherapy chemotherapy remains the primary treatment option, though its limited efficacy contributes to the cancer’s high mortality rate. HER2-targeted therapy, a fully validated approach, has proven effective in breast and gastric cancers.
Furthermore, IBI354, a conjugate of an anti-HER2 monoclonal antibody and a camptothecin derivative, has demonstrated strong antitumor activity in platinum-resistant ovarian cancer with HER2 expression in previous studies. Notably, in patients with low HER2 expression (IHC 1+), IBI354 showed efficacy comparable to that in patients with higher HER2 expression. The news release further stated that the therapy has an excellent safety profile, with a very low risk of common or concerning toxicities associated with other antibody-drug conjugates, including interstitial lung disease, fatigue, diarrhea, hair loss and eye toxicity.
Glossary:
Disease control rate: the percentage of patients whose cancer shrinks or remains stable for a defined period.
Interstitial lung disease: a group of lung conditions causing scarring and inflammation, sometimes a side effect of cancer treatments.
Objective response rate: the percentage of patients whose cancer significantly shrinks after treatment.
Progression-free survival: the length of time a patient lives without the cancer worsening.
Antibody-drug conjugate: a targeted cancer therapy combining a monoclonal antibody with a cytotoxic drug to selectively kill cancer cells.
Camptothecin derivative: a type of chemotherapy drug derived from camptothecin, which inhibits topoisomerase I, an enzyme necessary for DNA replication in cancer cells.
Monotherapy: treatment using a single drug rather than a combination of drugs.
“I look forward to positive results from the HeriCare-Ovarian01 study. It is hoped that IBI354 may provide survival benefits to [patients with platinum-resistant ovarian cancer] with varying levels of HER2 expression,” Zhou concluded.
After a median follow-up of 6.5 months, the overall objective response rate in the previous multicenter phase 1/2 study of IBI354 was 40.2%, and the disease control rate was 81.6%. Among 40 participants with ovarian cancer treated with 12 milligrams per kilogram every three weeks, the objective response rate was 52.5%, and the disease control rate was 90%. In 27 participants with HER2 IHC 1+ in the same dosing group, the objective response rate was 55.6%, and the disease control rate was 88.9%. The study included 87 participants with platinum-resistant ovarian cancer who were treated with IBI354 at doses ranging from 6 to 12 milligrams per kilogram, with 77% having received at least three prior anti-tumor regimens.
Additionally, in the phase 1/2 clinical study, which included 368 participants, no dose-limiting toxicities occurred up to the 18 milligram per kilogram dose group. The overall incidence of grade 3 (severe) or higher treatment-related side effects was 21.5%, with 12.2% of participants experiencing treatment-related side effects that led to dose interruption, 2.4% experiencing effects that led to dose reduction and 1.6% experiencing effects that led to discontinuation.
No treatment-related side effects resulted in death. The most common treatment-related side effects were nausea, decreased white blood cell count and anemia. The incidence of interstitial lung disease was 1.6%, with all cases classified as grade 1 (mild).
"We are pleased to complete the first patient enrollment for the HeriCare-Ovarian01 study at our site,” professor Tao Zhu, Zhejiang Cancer Hospital, and collaborating investigator said in the release. “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. As an anti-HER2 [antibody drug conjugate], preliminary findings from IBI354 have demonstrated encouraging objective response rates and disease control rates in [platinum-resistant ovarian cancer]. Furthermore, IBI354 exhibits a superior clinical safety profile and treatment tolerability compared to other [antibody drug conjugates].”
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