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.
Domenica Lorusso, Ignace Vergote, Roisin E. O’Cearbhaill, Anneke M. Westermann, Susana Banerjee, Els Van Nieuwenhuysen, David A. Iglesias, Dearbhaile Catherine Collins, David Cibula, Kristine S. Madsen, Krishnansu S. Tewari, Sandro Pignata, Jean‐François Baurain, Ingrid Boere, Hannelore Denys, Camilla Mondrup Andreassen, Ibrahima Soumaoro, Shweta Jain, Christine Gennigens, Bradley J. Monk
Abstract
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.