On May 29, 2022 InxMed Co., Ltd, a clinical-stage biotechnology company dedicates on developing innovative therapies targeting stroma microenvironment and drug resistance for hard-to-treat solid tumors, reported that the clinical data from an open-label phase Ib trial evaluating the efficacy and safety of IN10018, a highly potent and selective oral inhibitor of focal adhesion kinase (FAK), in combination with pegylated liposomal doxorubicin (PLD) in patients with platinum-resistant recurrent ovarian cancer (PROC), will be presented in the form of poster at the upcoming 2022 annual meeting of American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) from June 3, 2022 to June 7, 2022 (Press release, InxMed, MAY 29, 2022, View Source [SID1234615222]). Abstract was published on the ASCO (Free ASCO Whitepaper)’s website（Abstract #：5567）. The data showed that patients receiving combination of IN10018 with PLD demonstrated promising antitumor activities and manageable safety profile in PROC patients, with a high overall response rate (ORR) of 56.7%（Poster #：445）.
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This phase Ib study is to evaluate the safety, tolerability, and antitumor activities of IN10018 in combination with PLD in patients with platinum-resistant recurrent ovarian cancer. The primary endpoint for the study is objective response rate (ORR), and key secondary endpoint include disease control rate (DCR), duration of response (DOR) and progress-free survival (PFS).
As of cutoff data of December 31, 2021, a total of 42 patients were enrolled. Antitumor response was evaluated in 30 efficacy evaluable patients who had at least one post-baseline tumor assessments per investigator’s assessment. 17 PRs and 9 SDs were reported and none of the patients had CR. The ORR was 56.7%, the DCR was 86.7%, and the median DOR was 4.5 months (95% confidence interval [CI]: 2.7 months – NA) and still maturing. The ORR and DCR were 65.0% (13/20) and 90.0% (18/20), respectively, in 20 efficacy evaluable patients who had at least 6 months follow-up. In all 42 enrolled patients, the median PFS were 6.2 months (95% CI: 6.2 months – NA) and still maturing.
The safety profile of the combination is comparable to these single agents alone without additive toxicities. No IN10018 related death observed and only 9.5% (4/42) patients reported SAEs which were related to both IN10018 and PLD. The most frequently reported IN10018 related AEs were proteinuria, decreased appetite, fatigue, and AEs of gastrointestinal origin such as nausea, diarrhea, vomiting. Majority of these drug related AEs were CTCAE grade 1 and 2, no drug related grade 4 or 5 AE reported. Proteinuria was noted asymptomatic, reversible and could be managed with appropriate dose interruption/reduction and only one proteinuria event resulted in IN10018 dose reduction.
"We are extremely pleased with the data as it demonstrates the superior efficacy and safety of our IN10018, as well as confirming the proof of mechanism of IN10018 regimen. We are excited by this outcome and are working hard on completing this study and determining the further design for a subsequent pivotal study," said Dr Zaiqi Wang, CEO of InxMed. FAK is a non-receptor tyrosine kinase that plays an important role in cell adhesion, migration, and regulation. It exhibits expression upregulation in multiple tumor types. Researchers have found that inhibiting the FAK signaling pathway can effectively reverse previously failed chemotherapy and targeted therapy caused by drug resistance and enhance the response and efficacy of immunotherapy for solid tumors.
InxMed set up a global clinical development program for IN10018, as one of the most advanced FAK inhibitors. Clinical trials currently underway in the US and China are designed for platinum-resistant ovarian cancer, NRAS mutant metastatic melanoma, triple-negative breast cancer, head and neck cancer, pancreatic cancer, and other solid tumors that are still lacking effective treatment. IN10018 received fast track designation from the U.S. Food and Drug Administration (FDA) in August 2021, and breakthrough designation from China National Medical Products Administration (NMPA) for the treatment of patients with platinum-resistant ovarian cancer.
InxMed has the exclusive global development and commercial operation rights of IN10018 and is planning to initiate a pivotal trial in the second half of the year.