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

Background

• Tisotumab vedotin (TV) is an investigational antibody-drug conjugate composed of a tissue factor-directed human monoclonal antibody covalently linked to cytotoxic MMAE.
• 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 of TV vs investigator’s choice of chemotherapy in pts with r/mCC following 1L therapy are presented.

Methods

• 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 pts were randomized (TV: 253; chemotherapy: 249)
• Median survival follow-up was 10.8 mo (95% CI, 10.3-11.6).
• Overall, median age was 50 yrs (range: 26-80)
• Arms were balanced for demographics and disease characteristics
• 63.9% and 27.5% of patients had prior bevacizumab and prior anti-PD-(L)1 therapy, respectively.
• The TV arm had a 30% reduction in risk of death vs chemotherapy (HR 0.70; 95% CI 0.54-0.89; P=0.0038), with significantly longer median OS (11.5 mo [95% CI 9.8-14.9] vs 9.5 mo [95% CI 7.9-10.7]).
• PFS was superior in the TV vs chemotherapy arm (HR: 0.67 [95% CI, 0.54-0.82]; P<0.0001).
• 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 at least 1 treatment-related adverse event (TV: 87.6% [grade ≥3: 29.2%] vs chemotherapy: 85.4% [grade ≥3: 45.2%]).
• AEs were consistent with the known TV safety profile, including for ocular, peripheral neuropathy, and bleeding AEs.

Conclusions

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

Vergote IB, Gonzalez Martin A, Fujiwara K et al. innovaTV 301/ENGOT-cx12/GOG-3057: A global, randomized, open-label, phase III study of tisotumab vedotin vs investigator’s choice of chemotherapy in 2L or 3L recurrent or metastatic cervical cancer. Abstract presented at: ESMO Congress 2023, October 20-24, 2023.