Abstract
ObjectivesTisotumab vedotin (TV) monotherapy has shown a manageable and tolerable safety profile with clinically meaningful and durable antitumor activity in previously treated r/mCC (Lancet Oncol. 2021;22:609–619). The potential of investigational TV combination regimens in r/mCC was assessed in a multi-cohort phase 1b/2 trial (NCT03786081).MethodsPatients with r/mCC with progression on/after or ineligible for/intolerant to standard-of-care were treated with escalating doses of TV + bevacizumab (Arm A) or pembrolizumab (Arm B) or carboplatin (Arm C) all given Q3W (figure 1). Primary objectives were to determine recommended phase 2 dosing (RP2D) and evaluate safety/tolerability.ResultsA maximum tolerated dose was not reached with any combination. In Arm A, 15 patients received 9 cycles (median) for both TV and bevacizumab. Grade≥3 adverse events (AEs) occurred in 5 patients (33%). The RP2D was TV 2.0 mg/kg + bevacizumab 15 mg/kg Q3W. Five patients had confirmed objective response (cOR). In Arm B, 13 patients received a median of 5 cycles of TV and 4 cycles of pembrolizumab. Grade≥3 AEs occurred in 12 patients (92%). The RP2D was TV 2.0 mg/kg + pembrolizumab 200 mg Q3W. Two patients had cOR. In Arm C, 13 patients received 5 cycles (median) of TV + 4 cycles of carboplatin. Grade≥3 AEs occurred in 8 patients (62%). The RP2D was TV 2.0 mg/kg + carboplatin AUC 5 Q3W. Four patients had cOR.Abstract O013/#573 Figure 1AUC, area under the curve; DL, dose level; DLT, dose-limiting toxicity; TV, tisotummab vedotin.Drugs administered IV on day 1 of 21-day cycle.Patients were treated for at least 2 cycles to evaluate DLTs.Escalation to the next DL was permited when fewer than 1 in 3 patients at the current DL experienced a DLT.The recommended phase 2 does (RP2D) was highest planned DL reached with DLTs in no more than 1 in 6 patients.ConclusionsTV plus bevacizumab, pembrolizumab, or carboplatin was tolerated and had an acceptable safety profile with encouraging activity in patients with r/mCC.