Objectives Tisotumab 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).
Methods Patients 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.
Results A 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.
Conclusions TV plus bevacizumab, pembrolizumab, or carboplatin was tolerated and had an acceptable safety profile with encouraging activity in patients with r/mCC.
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