Background: IN10018 is a highly potent and selective oral inhibitor of focal adhesion kinase (FAK). IN10018 is synergistic with PLD against ovarian cancer in PDX models. This study evaluated the safety, tolerability, and antitumor activities of IN10018 in combination with PLD in patients with platinum-resistant ovarian cancer (PROC). Methods: This is an open-label phase Ib trial in patients with PROC (high-grade serous carcinoma only). Patient were treated with IN10018 in combination with PLD. This study has a dose-confirmation part and a dose-expansion part. Dose-expansion part was conducted at RP2D dose level to evaluate the primary endpoint of objective response rate (ORR). Secondary endpoints included disease control rate (DCR, CR + PR + SD ≥ 6 weeks), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results: As of December 31, 2021 (cutoff date for all assessments), a total of 42 PROC patients were enrolled. 92.9% (39/42) patients had 1-3 prior lines of therapy and 14.3% (6/42) had prior bevacizumab use. The RP2D of the combination was determined as IN10018 100 mg QD in combination with PLD 40 mg/m² Q4W in the dose-confirmation part since no DLTs were observed in 6 patients treated. The safety profile of the combination is comparable to these single agents alone without additive toxicities. No IN10018 related death was observed, and 9.5% (4/42) patients reported IN10018 related SAEs which were also PLD related. 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 IN10018 related AEs were CTCAE grade 1 and 2, and 14.3% (6/42) had grade 3 AEs. No IN10018 related grade 4 or 5 AEs were reported. Proteinuria was noted asymptomatic, reversible, could be managed with appropriate dose interruption/reduction and only one proteinuria event resulted in IN10018 dose reduction. Antitumor response (as assessed by investigator) was evaluable in 30 patients. 17 patients had best overall response of PR including 13 confirmed PRs and 4 unconfirmed (2 in follow-up to be confirmed). No patient had CR and 9 patients had SD. The ORR is 56.7% (95% CI: 37.4%, 74.5%), the DCR is 86.7% (95% CI: 69.3%, 96.2%), and the median DOR was 4.5 months (95% CI: 2.7 months – NA) and is continuing to mature. Among the 20 efficacy evaluable patients who had at least 6 months of follow up, the ORR is 65.0% (13/20, 95% CI: 40.8%, 84.6%) and the DCR is 90.0% (18/20, 95% CI: 68.3%, 98.8%). In all 42 enrolled patients, the observed median PFS is 6.2 months (95% CI: 6.2 months - NA) and maturing. Conclusions: The combination of IN10018 with PLD showed promising antitumor activities and manageable safety profile in PROC patients. This combination warrants further confirmation in a randomized controlled trial.