Abstract 140P
Background
Immune-checkpoint inhibitor (ICI) combined with chemotherapy have been approved as first-line therapy for BTC. However, the efficacy of subsequent standard of care is limited. Tinengotinib (TT) is a novel multi-kinase inhibitor that targets cell proliferation, angiogenesis, and immune-oncology pathways by inhibiting Aurora kinases A/B, Janus kinases and receptor tyrosine kinases (FGFRs and VEGFRs). Here we present the data of TT in combination with atezo in pts with BTC from a phase Ⅰb/Ⅱ trial in China.
Methods
Eligible pts with advanced BTC were enrolled and treated with TT plus atezo 1200 mg in 21-day cycle, including pts with prior ICI(s). Dose escalation (Phase Ib) and dose expansion (Phase II) were designed.
Results
As of 31-May-2024, 31 pts with median age 59.0 years had been enrolled (median follow-up: 6.7 mos). 67.7% were male, 90.3% had ECOG of 1, 80.6% were FGFR wild type, 61.3% had ≥ 2 lines of prior therapies, 71.0% had prior ICI(s), and 100% were MSS. PD-L1 CPS was ≥10 in 3 (21.4%) of 14 tested. No DLT was observed in Phase Ib (3 pts in each group of TT 8, 10, 12 mg QD plus atezo). 8 and 10 mg QD were selected as alternative dose levels in Phase II. All 31 pts were efficacy evaluable. The objective response rate (ORR) and disease control rate (DCR) were 19.4% and 74.2%, the mPFS reached 4.21 (95% CI, 2.27-NA) mos. Among 28 cholangiocarcinoma (CCA) pts, the ORR and DCR were 21.4% and 75.0%, the mPFS reached 6.77 (95% CI, 2.43-NA) mos. Similar efficacy was observed regardless of prior ICI(s) therapy. TRAEs were reported in 31 (100%) pts, Gr ≥ 3 in 18 (58.1%) pts. The most common TRAEs (Gr3/4 ≥5%) included hypertension (22.6%), neutropenia, thrombocytopenia (12.9%), palmar-plantar erythrodysesthesia syndrome (9.7%), and diarrhea (6.5%). No Gr 5 TRAE were observed.
Conclusions
TT combined with atezo has promising antitumor activities and well-tolerated safety profiles in heavily pre-treated BTC pts. The results support a further study to evaluate the safety and efficacy of TT plus ICI in BTC pts who had prior ICI and/or chemotherapy.
Clinical trial identification
NCT05253053.
Editorial acknowledgement
Legal entity responsible for the study
TransThera Sciences (Nanjing), Inc.
Funding
TransThera Sciences (Nanjing), Inc.
Disclosure
All authors have declared no conflicts of interest.