Preliminary safety and efficacy of tinengotinib tablets as monotherapy and combination therapy in advanced solid tumors: A phase Ib/II clinical trial.

• DOI: 10.1200/jco.2023.41.16_suppl.3019
• Publication Date: 2023-06-04T15:23:35Z
• Authors: Sarina A. Piha-Paul; Sanjay Goel; Chih-Yi Liao; Nashat Y. Gabrail; Farshid Dayyani; Syed Mohammad Ali...; Yuan Yuan; Sayeh Moazami Lav...; Jean Fan; Peng Peng; Caixia Sun; Hui Wang; Katie Hennessy; Ximei Fu; Shumao Ni; Hui Xian Tan; Brenda Ngo; Qinhua Cindy Ru; Frank Wu; Milind M. Javle
• Keywords: Tolerability; Combination therapy

3019 Background: Tinengotinib is a spectrum-selective multi-kinase inhibitor that targets cell proliferation, angiogenesis, and immune-oncology pathways by inhibiting Aurora kinases A/B, Janus (JAK), receptor tyrosine (FGFRs, VEGFRs). has shown preliminary efficacy in prostate cancer (PC), hormone positive (HR+)/human epidermal growth factor 2 negative (HER2-) breast (BC), triple-negative BC (TNBC) cholangiocarcinoma (CCA) Phase (Ph) 1 trial. Here we present the safety, pharmacokinetics (PK), of tinengotinib Ph Ib/II Methods: Eligible patients (pts) with advanced or metastatic solid tumors were assigned to: Arm A (tinengotinib 12 mg QD), B 8/10/12 QD combination 100 mg/m Abraxane, HER2- BC); C PK Run-in 5/8/10/12 QD, 4/6 BID). Objectives include safety (CTCAE v5.0) tolerability, profile, (RECIST v1.1) exploratory biomarker(s). Results: As 30 Jan 2023, 157 pts enrolled treated. In monotherapy (Arm C, N=153), median age was 62.5 years (23-83), 56% female, 69% had ≥ 3 prior lines therapy. B, N=4), 40 (25-46), 100% ≥3 The treatment-related AEs (TRAE) arms reported 110 (71.9%) pts. 53 (34.6%) Grade (G) 1-2, 55 (35.9%) G3, (1.3%) G4, no G5 observed; most common TRAEs hypertension (29.4%), stomatitis (20.9%), diarrhea (16.3%), nausea (13.7%) palmar-plantar erythrodysesthesia syndrome (12.4%). arm, 4 treated at dose level experienced G3 TRAEs, neutropenia (75%), (50%), hyponatremia hypokalemia (50%) (50%). 108 efficacy-evaluable arms, overall response rate (ORR) disease control (DCR) 16% 60%, respectively. ORR PC, HR+/HER2- BC, TNBC CCA 50% (5/10), 40% (2/5), (3/6) 20% (3/15), Preliminary analysis showed linear increase on exposure terms geometric mean max,ss AUC 0-24h,ss from 5 to QD. No significant difference observed vs BID. Conclusions: well-tolerated. tolerability assessment chemotherapy underway. results may support recommendation for subsequent trials. Encouraging anticancer activity heavily pre-treated tumors, including CCA. ongoing II study continues evaluate clinical benefit PC. Clinical trial information: NCT04742959 .