Seagen Inc. and Genmab A/S presented interim data from two cohorts of the phase 1b/2 innovaTV 205 multi-cohort, open-label trial of tisotumab vedotin in recurrent or metastatic cervical cancer at the European Society for Medical Oncology (ESMO) Virtual Congress 2021 as part of a featured mini oral presentation. Initial results from these two dose expansion cohorts of the study showed encouraging and durable anti-tumor activity with tisotumab vedotin in combination with carboplatin (Cohort D) as first-line therapy for patients with advanced cervical cancer who had not received prior systemic therapy, with a 55% objective response rate (ORR) and with tisotumab vedotin in combination with pembrolizumab (Cohort F) for patients with advanced cervical cancer who experienced disease progression after 1-2 lines of prior systemic therapy, with a 38% ORR. Both combinations demonstrated a manageable and acceptable safety profile, with no new safety signals identified.

1L TV + Carbo Dose Expansion Cohort Interim Results Within this cohort, recurrent or metastatic cervical cancer patients who had not received any prior systemic therapy were given the recommended phase 2 dose of tisotumab vedotin 2.0 mg/kg plus carboplatin AUC 5 Q3W. Efficacy: The primary endpoint of ORR was 55% (n=18/33 patients), with four patients achieving complete responses and 14 patients achieving partial responses. Median time to response was 1.4 months (range 1.1-4.4), with median follow up of 7.9 months and median duration of response of 8.3 months (95% CI: 4.2-NR).

Median progression-free survival (PFS) was 9.5 months (95% CI: 4.0-NR). Safety: Grade =3 adverse events (AE) occurred in 78.8% of patients (n=26/33), with 57.6% (n=19/33) of patients experiencing Grade =3 AEs related to treatment with tisotumab vedotin. Adverse events of special interest (AESI) included ocular events (Grade 1-2: 57.6%; Grade =3: 9.1%), bleeding (Grade 1-2: 51.5%; Grade =3: 6.1%) and peripheral neuropathy (Grade 1-2: 48.5; Grade =3: 12.1%).

2L/3L TV + Pembro Dose Expansion Cohort Results Interim Results Within this cohort, recurrent or metastatic cervical cancer patients who had received 1-2 prior systemic therapies were given the recommended phase 2 dose of tisotumab vedotin 2.0 mg/kg plus pembrolizumab 200 mg Q3W. Efficacy: The primary endpoint of ORR was 38% (n=13/34 patients), with two patients achieving complete responses and 11 patients achieving partial responses. Median time to response was 1.4 months (range 1.3-5.8), with median follow-up of 13.0 months and a median duration of response of 13.8 months (95% CI: 2.8-NR).

Median PFS was 5.6 months (95% CI: 2.7-13.7). Safety: Grade =3 AEs occurred in 74.3% of patients (n=26/35), with 45.7% (n=16/35) of patients experiencing Grade =3 AEs related to treatment with tisotumab vedotin. AESI included ocular events (Grade 1-2: 51.4%; Grade =3: 2.9%), bleeding (Grade 1-2: 57.1%; Grade =3: 8.6%) and peripheral neuropathy (Grade 1-2: 37.1%; Grade =3: 2.9%), with one patient experiencing a Grade 4 bleeding event.