A Ph-Ib study of TRK-950 combined with anti-cancer treatment regimens in patients with advanced solid tumors

Background: TRK-950 is a first-in-class humanized antibody raised against CAPRIN-1 which we have identified as a novel and universal target for cancer therapies. TRK-950 strongly and specifically binds to various cancer cells and shows anti-tumor effects via engagement of immune cells. A series of pre-clinical studies demonstrates its potency and safety. In the phase I study of TRK-950 monotherapy (NCT02990481), it appears safe and well tolerated. No DLT was observed and MTD was not reached at doses of 3–30 mg/kg IV weekly. Here, we report on select cohorts of the ongoing, multicenter phase Ib study of TRK-950 combined with standard of care (SOC) regimens in patients (pts) with advanced cancers (NCT03872947). Materials and Methods: Pts with colorectal cancer (CRC), cholangiocarcinoma (CCA), gastric/GEJ (GC) and ovarian cancer (OC) with measurable disease were enrolled in separate cohorts. Pts with CRC received FOLFIRI on D1, 15 of a 28-day cycle. Pts with CCA received Gemcitabine/Cisplatin on D1, 8 of a 21-day cycle. Pts with OC received Gemcitabine on D1, 8 and Carboplatin on D1 of a 21-day cycle. Pts with GC received Paclitaxel on D1, 8, 15 and Ramucirumab on D1, 15 of a 28-day cycle. TRK-950 was given 10 mg/kg IV weekly in all cohorts. Each cohort consists of ≥6 pts and DLT was evaluated during the first cycle. Response was assessed every 2 cycles. Primary endpoint was safety and tolerability. Secondary endpoints incl. overall response rate (ORR), disease control rate (DCR) per REClST v1.1. Tumor CAPRIN-1 expression was measured by IHC. Results: A total of 75 pts have been enrolled and received at least 1 dose of TRK-950, incl. 44 pts with four representative solid tumors: 14 pts with CRC, 11 pts with CCA, 10 pts with OC, 9 pts with GC. Median age 60 yrs; Karnofsky performance status 70 (7%), 80 (23%), 90 (48%), 100 (23%); 52% male, 48% female. Most common all-grade treatment-related AEs (TRAEs) in ≥10% of all pts were fatigue (34%), nausea (27%), neutrophil count decreased (16%), diarrhea (11%), vomiting (11%) and white blood cell count decreased (11%). Most common grade ≥3 TRAE in ≥10% of pts was neutrophil count decreased (14%). In response evaluable pts, ORR was 21% in CRC, 27% in CCA, 33% in OC and 56% in GC. DCR was 57% in CRC, 82% in CCA, 78% in OC and 100% in GC. Conclusions: TRK-950 binds to a newly described target, CAPRIN-1, and has an acceptable safety and tolerability profile when combined with SOC chemotherapy in multiple cancers. Preliminary clinical activity is demonstrated in pre-treated patients with encouraging response rates and high disease control rates, particularly in OC and GC. Further antitumor activity is being confirmed for cancer types for which such a notable response rate has been obtained. Conflict of interest: Other Substantive Relationships: Dr. Okano - Director of TORAY