Tisotumab vedotin (TV) + pembrolizumab (pembro) in first-line (1L) recurrent or metastatic cervical cancer (r/mCC): Interim results of ENGOT Cx8/GOG 3024/innovaTV 205.

5507 Background: TV monotherapy has received US accelerated approval for previously treated r/mCC with disease progression on or after chemotherapy based on clinically meaningful tumor response rate and duration of response (DOR) reported from the GOG-3023/ENGOT-cx6/innovaTV 204 study (Coleman et al., Lancet Onc. 2021). Recently, the recommended phase 2 dose (RP2D) and feasibility of TV + pembro, TV + carboplatin (carbo), and TV + bevacizumab in r/mCC were reported from the dose-escalation phase (Monk et al, IGCS 2021); interim safety and efficacy data from 2 dose-expansion cohorts, 1L TV + carbo and second-line/third-line (2L/3L) TV + pembro (Vergote et al, ESMO 2021) from the ENGOT-cx8/GOG-3024/innovaTV 205 (NCT03786081) study, were also reported. Here we report interim safety and efficacy results from a third dose-expansion cohort evaluating 1L TV + pembro in patients with r/mCC. Methods: Patients with r/mCC who had not received prior systemic therapy (excluding chemoradiation) for r/mCC were treated with the RP2D of TV 2.0 mg/kg + pembro 200 mg intravenously every 3 weeks. The primary endpoint was investigator-assessed confirmed objective response rate (ORR) per RECIST v1.1; secondary endpoints included DOR, progression-free survival (PFS), overall survival (OS), and safety. Results: 33 pts were treated with 1L TV + pembro (median 6 cycles). At data cutoff (July 1, 2021), median duration of exposure to TV + pembro was 5.1 mo (range 1-17) and median follow-up was 12.2 mo (range 1-17). Confirmed ORR among 32 evaluable patients was 41% (95% CI 24-59), with 3 (9%) complete responses and 10 (31%) partial responses. Median time to response was 1.4 mo (range 1.2-2.8); median DOR was not reached, with response ongoing in 7/13 patients. Median PFS was 5.3 mo (95% CI 4.0-12.2); median OS was not reached. The most common treatment-emergent AEs (TEAEs) were alopecia (61%), diarrhea (55%), epistaxis (49%), conjunctivitis (46%), and nausea (46%). Grade ≥3 TEAEs occurred in 67% of patients, the most common being anemia (12%); asthenia (9%); hypokalemia (9%); and increased alanine aminotransferase, decreased white blood cell count, dyspnea, and acute kidney injury (6% each). Three grade 5 TEAEs were reported of which one, disseminated intravascular coagulation, was considered treatment-related. Prespecified AEs of interest (grade 1-2/grade ≥3) with TV included ocular (58%/9%), peripheral neuropathy (45%/3%), and bleeding (61%/6%). Updated results with longer follow-up for this cohort and the 1L TV + carbo and 2L/3L TV + pembro cohorts will be provided at the meeting. Conclusions: TV + pembro demonstrated encouraging, durable antitumor activity with a manageable and acceptable safety profile as a 1L regimen for patients with r/mCC. This trial is ongoing and final analyses will be reported in the future. Clinical trial information: NCT03786081.