398P - A phase Ib/II study of IN10018/FAKi in combination with pegylated liposomal doxorubicin (PLD) and toripalimab in metastatic triple-negative breast cancer (TNBC): IN10018-010

Background

IN10018 is a highly potent and selective oral inhibitor of focal adhesion kinase (FAK). Preclinical data showed that IN10018 in combination with PLD had synergistic antitumor effect and can further enhance immunotherapeutic effect in TNBC animal model. This study was to evaluate the safety and antitumor activity of IN10018 combined with PLD +/- anti-PD-1 antibody, Toripalimab in metastatic TNBC.

Methods

All enrolled metastatic TNBCs who had failed in 1-2 lines of systemic therapy were assigned to either doublet group: IN10018+PLD or triplet group: IN10018+PLD+Toripalimab. Phase Ib-dose finding part was to identify the recommended phase II dose (RP2D) of triplet combination. Phase II-dose expansion part was to evaluate the primary endpoint of objective response rate (ORR) and secondary endpoints of disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety.

Results

At data cutoff of April 28, 2023, 12 pts received IN10018+PLD and 14 pts received IN10018+PLD+Toripalimab. Median follow-up duration was 7.2 mo (range: 4.9-9.7) in doublet group and 6.0 mo (range: 2.0-10.5) in triplet group. The RP2D was determined as IN10018 100mg qd + PLD 40mg/m² q4w + Toripalimab 3 mg/kg q2w. In doublet group, ORR by investigators was 16.7% (95% CI, 2.1-48.4); DCR was 50% (95% CI, 21.1-78.9); median PFS was 3.65 mo (95% CI, 1.77-NA); and median OS was 7.52 mo (95% CI, 5.59-NA). In triplet group, ORR by investigators was 14.3% (95% CI, 3.8-42.8); DCR was 78.6% (95% CI, 49.2-95.3); median PFS was 9.26 mo (95% CI, 3.02-NA); and median OS was not reached. No drug-related death was observed. In doublet group, TEAEs grade ≥3 occurred in 58.3% pts with TEAEs in ≥2 pts being WBC and neutrophil count decreased; SAE occurred in 2 pts with 1 related to treatment. In triplet group, TEAEs grade ≥3 occurred in 64.3% pts with TEAEs in ≥2 pts being anemia, WBC and neutrophil count decreased; SAE occurred in 5 pts with 4 related to treatment.

Conclusions

The combination of IN10018 with PLD and Toripalimab showed promising antitumor activity in metastatic TNBC. The combination safety profile was comparable to each single agent with no additional safety signal.

Clinical trial identification

NCT05830539.

Editorial acknowledgement

Legal entity responsible for the study

InxMed (Shanghai) Co., Ltd, Shanghai, China.

Funding

InxMed (Shanghai) Co., Ltd, Shanghai, China.

Disclosure

All authors have declared no conflicts of interest.