Introduction/Background Tisotumab vedotin (TV) is an investigational antibody-drug conjugate directed to tissue factor. In the US, TV monotherapy received accelerated approval for the treatment of adult patients with recurrent or metastatic cervical cancer (r/mCC) with disease progression on or after chemotherapy. Here, innovaTV 301 (NCT04697628) study results are presented.

Methodology Eligible patients had r/mCC with disease progression on/after treatment with standard of care chemotherapy doublet ± bevacizumab ± anti-PD-(L)1 therapy, measurable disease per RECIST v1.1, and ECOG PS 0–1. Patients were randomized 1:1 to TV monotherapy or investigator’s choice of topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed. The primary endpoint was OS. Key secondary endpoints included PFS and confirmed ORR by investigator.

Results 502 patients were randomized (TV: 253; chemotherapy: 249); median survival follow-up was 10.8 months (95% CI, 10.3–11.6). Arms were balanced for demographics and disease characteristics, with 63.9% and 27.5% of patients receiving prior bevacizumab and prior anti-PD-(L)1 therapy, respectively. The TV arm had a 30% reduction in risk of death versus chemotherapy (HR 0.70; 95% CI 0.54–0.89; P=0.0038), with significantly longer median OS (11.5 months [95% CI 9.8–14.9] versus 9.5 months [95% CI 7.9–10.7]). PFS was superior in the TV versus chemotherapy arm (HR: 0.67 [95% CI, 0.54–0.82]; P<0.0001). The OS and PFS benefits in the prespecified subgroups were generally consistent with the ITT population. Confirmed ORR was 17.8% and 5.2% in the TV and chemotherapy arms, respectively (odds ratio: 4.0; 95% CI, 2.1–7.6; P<0.0001). Most patients experienced ≥1 treatment-related adverse event (TV: 87.6% [grade ≥3: 29.2%] versus chemotherapy: 85.4% [grade ≥3: 45.2%]). AEs were consistent with the known TV safety profile.

Conclusion In the phase 3 innovaTV 301 study, TV showed a statistically significant and clinically meaningful improvement in OS, PFS, and ORR versus chemotherapy, with a manageable and tolerable safety profile in patients with 2L/3L r/mCC.

Disclosures Previously presented in part at ESMO 2023, ‘LBA9: innovaTV 301/ENGOT-cx12/GOG-3057: A Global, Randomized, Open-Label, Phase 3 Study of Tisotumab Vedotin vs Investigator’s Choice of Chemotherapy in 2L or 3L Recurrent or Metastatic Cervical Cancer ‘, Ignace Vergote et al. - Reused with permission.