753P - IN10018 in combination with pegylated liposomal doxorubicin (PLD) in platinum-resistant ovarian cancer (PROC): A single-arm, phase Ib clinical trial

Background

IN10018 is a highly potent and selective oral inhibitor of focal adhesion kinase (FAK). Our previous work showed promising objective response rate (ORR) and progression-free survival (PFS) of IN10018 in combination with PLD in PROC patients (Wu et al, ASCO2022). Here we present the fully enrolled study data, especially the overall survival (OS).

Methods

In this single-arm, open-label, phase Ib trial, PROC pts (high-grade serous only) received IN10018 in combination with PLD treatment until intolerable toxicity or disease progression. The primary endpoint was ORR, the second endpoints including disease control rate (DCR), duration of response (DOR), PFS, OS, and safety.

Results

As of April 28, 2023, a total of 61 PROC pts (median age 55 years) were enrolled with median follow-up duration of 14.0 months (range: 0.9 - 32.8 months). 90.2% (55/61) pts had 1-3 prior lines of therapy, 34.4% (21/61) had prior bevacizumab treatment and 27.9% (17/61) had prior PARPi treatment. The safety profile of the combination is comparable to these single agents alone without additive toxicities. No IN10018 related death was observed, and 9.8% (6/61) pts reported IN10018 related SAEs which were also PLD related. The most frequently reported IN10018 related AEs assessed by investigators were proteinuria, decreased appetite, fatigue and AEs of gastrointestinal origin such as nausea, diarrhea, vomiting. Majority of these IN10018 related AEs were grade 1 and 2. No IN10018 related grade 4 or 5 AEs were reported. Efficacy (as assessed by investigator) was evaluable in 54 pts. 25 responders (including 1 confirmed CR, 21 confirmed PRs and 3 unconfirmed PRs) and 20 SDs were reported. The ORR was 46.3% (95% CI: 32.6%, 60.4%), the DCR was 83.3% (95% CI: 70.7%, 92.1%). The mDOR was 6.9 months (95% CI: 4.2 – 9.1 months). The mPFS was 7.3 months (95% CI: 5.2 – 9.0 months). The mOS was 20.9 months (26/61 OS events, 95% CI: 14.4 – NA) in all treated population and maturing.

Conclusions

The combination of IN10018 with PLD showed manageable safety profile and prolonged survival in PROC pts. A placebo-controlled, randomized, double-blind phase II trial is ongoing to confirm the observed efficacy and safety.

Clinical trial identification

NCT05551507.

Editorial acknowledgement

Legal entity responsible for the study

InxMed (Nanjing) Co., Ltd.

Funding

InxMed (Nanjing) Co., Ltd.

Disclosure

S. Xie, J. Jiang: Financial Interests, Personal, Full or part-time Employment: InxMed (Nanjing) Co., Ltd. All other authors have declared no conflicts of interest.