INNOVENT BIO IBI354 shows good efficacy in advanced solid tumors, breast cancer, and advanced gynecological cancers

According to the Zhitong Finance and Economics APP, the 2024 European Society for Medical Oncology (ESMO) Annual Meeting will be held in Barcelona, Spain from September 13th to 17th local time. Recently, the ESMO conference website has just released the abstracts selected for Mini Oral presentations. Innovent Biologics (01801) targeting HER2 antibody-drug conjugate (ADC) IBI354 has two Phase 1 studies selected, which evaluate the safety and efficacy of IBI354 in late-stage solid tumors, breast cancer, and late-stage gynecological cancer patients. The reports show that in the treatment of late-stage solid tumors and breast cancer, the disease control rate (DCR) can reach 93.3%, while in the treatment of late-stage gynecological tumors, the DCR reaches 92.9%. IBI354 demonstrates good tolerability and efficacy in late-stage gynecological cancer patients.

IBI354 is an ADC product containing the anti-HER2 antibody trastuzumab and a topoisomerase I inhibitor. Currently, the product is undergoing Phase 1 clinical studies for various HER2-positive solid tumors.

IBI354 in the treatment of late-stage solid tumors and breast cancer, DCR can reach 93.3%

IBI354's global multicenter Phase 1 study in late-stage solid tumors and breast cancer patients was selected for the Mini Oral session of this ESMO conference. The study included patients who had failed standard treatment or were intolerant to it. IBI354 was administered at doses of 0.8 to 15mg/kg, every 3 weeks or every 2 weeks. Dose escalation selected a dose level of ≥6mg/kg. The primary endpoint was safety, and the secondary endpoints included objective response rate (ORR), disease control rate (DCR), median duration of response (DOR) according to RECIST v1.1, and progression-free survival (PFS).

As of March 22, 2024, a total of 318 patients from China and Australia who had received ≥2 prior treatment regimens were enrolled. The median duration of treatment was 14.2 weeks, with 215 patients (67.6%) still receiving treatment. No dose-limiting toxicities were observed at any dose level. Treatment-related adverse events (TRAEs) occurred in 257 patients (80.8%), with a ≥3 grade TRAE rate of 16.7% in all patients and 16.0% in the 12mg/kg Q3W cohort. Eleven patients (4.1%) experienced severe TRAEs, one patient (0.3%) required dose reduction, one patient (0.3%) required treatment discontinuation, and no TRAE-related deaths occurred. One patient (0.3%) experienced interstitial lung disease (grade 1).

Effectiveness data showed that as of April 25, 2024, 44 HER2-positive breast cancer patients had undergone at least one tumor assessment, with an ORR of 61.4% and a DCR of 88.6% The ORR and DCR of 6mg/kg Q3W were 57.1% and 85.7% respectively; 9mg/kg Q3W had ORR and DCR of 53.3% and 86.7% respectively; 12mg/kg Q3W had ORR and DCR of 73.3% and 93.3% respectively. 26 patients with low HER2 expression breast cancer underwent at least one tumor assessment, with a dosage of 12mg/kg Q3W, resulting in an ORR of 53.8% and DCR of 88.5%. DoR and PFS are still immature.

Researchers believe that IBI354 remains well tolerated at doses as high as 12mg/kg, and good efficacy has been observed in both HER2-positive and HER2-low breast cancer.

IBI354 achieves a DCR of 92.9% in the treatment of advanced gynecological tumors

A phase 1 study of IBI354 in the treatment of advanced gynecological cancers was also included in the mini oral session of this ESMO conference. In this study, patients with HER2 IHC 1+, 2+, or 3+ advanced cervical cancer (CC), endometrial cancer (EC), or platinum-resistant ovarian cancer (OC) who had failed standard treatment or were intolerant received IBI354 at doses of 6, 9, or 12mg/kg Q3W. The primary endpoint of the study was safety, with secondary endpoints including ORR, DCR, DoR, and PFS based on RECIST v1.1.

As of March 22, 2024, a total of 129 patients were enrolled, including 89 OC patients, 26 CC patients, and 14 EC patients. The median treatment duration was 12.3 weeks. The incidence of treatment-related adverse events (TRAEs) was 81.4% (105 cases), with a ≥3 grade TRAEs incidence of 16.3%. The most common TRAEs (≥20%) were anemia (34.1%), leukopenia (30.2%), nausea (29.5%), and neutropenia (21.7%). No interstitial lung disease was observed. The incidence of severe TRAEs was 7.0%. No TRAEs led to treatment interruption or death.

As of April 25, 2024, for patients who had undergone at least one tumor assessment (n=124), the ORR was 39.5% and the DCR was 83.1%. For OC patients, the ORR was 41.9% and the DCR was 81.4%; for 40 OC patients treated with a dose of 12mg/kg, the ORR and DCR were 45.0% and 90.0% respectively. For 14 HER2 2/3+ CC and EC patients, the ORR and DCR were 57.1% and 92.9% respectively, with one endometrial cancer patient achieving complete remission and seven (4 cervical cancer and 3 endometrial cancer) achieving partial remission DoR and PFS are not mature yet. Researchers believe that IBI354 is well tolerated in late-stage gynecological cancer patients and shows good efficacy