Tisotumab Vedotin Combo Elicits Responses in Frontline Recurrent Cervical Cancer

Treatment with tisotumab vedotin-tftv (Tivdak) in combination with carboplatin and pembrolizumab (Keytruda), with or without bevacizumab (Avastin), demonstrated antitumor activity in patients with frontline recurrent or metastatic cervical cancer. These findings from arm H of phase 1/2 ENGOT-cx8/GOG-3024/innova TV 205 (NCT03786081) were presented at the 2026 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.¹

Data from arm H (n = 38) showed that the triplet/quadruplet elicited a confirmed objective response rate (ORR) of 65.8% (95% CI, 48.6%-80.4%), which comprised a complete response rate of 18.4% and a partial response rate of 47.4%; the stable disease rate was 26.3% and 7.9% of patients had progressive disease. The confirmed disease control rate was 92.1% (95% CI, 78.6%-98.3%). Almost all patients experienced a decrease in size of target lesions.

Moreover, the median time to response was 2.1 months (range, 1.4-4.2) and the median duration of response (DOR) was 13.3 months (range, 6.1-not reached [NR]). Regarding survival outcomes, the median progression-free survival (PFS) was 10.6 months (95% CI, 6.8-17.8) and the 2-year PFS rate was 29.3% (95% CI, 15.3%-44.8%). The median overall survival (OS) was 28.0 months (95% CI, 19.7-NR) and the 2-year OS rate was 62.4% (95% CI, 44.9%-75.8%).

“Tisotumab vedotin in combination with carboplatin and pembrolizumab with or without bevacizumab was feasible and resulted in robust antitumor activity, leading to encouraging survival outcomes in first-line recurrent or metastatic cervical cancer,” Toon Van Gorp, MD, PhD, a gynecologic oncologist at University Hospital Leuven, KU Leuven, in Belgium, said in a presentation of the data. “In a proof-of-concept study, the primary end point, ORR, was 65.8%...The safety profile of the triplet and quadruplet combination was consistent with the known profile of each individual agent and toxicities were as expected. These findings really highlight the versatility of tisotumab vedotin to combine with standard-of-care treatments.”

How was innovaTV 205 designed?

the phase 1b, dose-escalation phase of the research was comprised of three arms. Those in arm A (n = 15) received tisotumab vedotin plus bevacizumab, those in arm B (n = 13) received tisotumab vedotin plus pembrolizumab, and those in arm C (n = 13) received tisotumab vedotin plus carboplatin. In this portion of the research, no dose-limiting toxicities were reported, the maximum tolerated dose was not reached, and the recommended phase 2 dose was identified. It was found that the regimens had an acceptable safety profile and “encouraging” antitumor activity.

The phase 2 dose-expansion portion of the study enrolled patients with recurrent or metastatic cervical cancer irrespective of PD-L1 status or tissue factor expression.² Patients were required to be at least 18 years of age, have measurable disease at baseline per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, and not have previously received systemic therapy for recurrent or metastatic disease.

The phase 2 portion is comprised of four arms. Those in arm D (n = 33), who are given first-line tisotumab vedotin plus carboplatin; those in arm E (n = 33), who are given frontline tisotumab vedotin plus pembrolizumab; those in arm F (n = 35), who are given second- or third-line tisotumab vedotin plus pembrolizumab; and those in arm H (n = 38).

Specifically, for arm H, patients received tisotumab vedotin at 2.0 mg/kg every 3 weeks (Q3W) plus carboplatin at area under the curve 5 Q3W, and pembrolizumab at 200 mg Q3W with or without bevacizumab at 15 mg/kg Q3W. In addition to the primary end point being ORR by investigator assessment and RECIST 1.1 criteria, secondary end points comprised DOR, PFS, OS, and adverse effects (AEs).

What were the baseline and disease characteristics of the patients who comprised arm H?

The median patient age was 48 years (range, 32-74). Most patients had an ECOG performance status of 0 (68.4%) and PD-L1 positivity defined as combined positive score of at least 1 (84.2%). More than half, or 63.2%, of patients had squamous histology; 34.2% of patients had adenocarcinoma and 2.6% had another histology. Moreover, 13.2% of patients had metastatic disease at diagnosis whereas 73.7% did not; this information was not known for 13.2% of patients.

In terms of previous therapy, 34.2% had received chemoradiotherapy or radiotherapy with surgery, 39.5% had prior chemoradiotherapy or radiotherapy only, 2.6% had chemotherapy with surgery, and 7.9% only underwent surgery; 15.8% of patients had no prior therapy. At the time of study entry, 23.7% of patients had persistent or recurrent disease without distant metastases, 52.6% had persistent or recurrent disease with distant metastases, and 23.7% had metastatic sites only. The median time since primary chemoradiotherapy or radiotherapy was 12.4 months and 13.3 months, respectively.

The median follow-up for arm H was 34.5 months (95% CI, 33.6-36.1) and the data cutoff date was October 15, 2025. Of the 38 total patients, 97.4% had discontinued treatment, the most common reasons being radiographic disease progression (55.3%), AE (21.1%), and other (13.2%); 5.3% of patients discontinued due to clinical progression. Moreover, 2.6% of patients were still receiving treatment at data cutoff and 36.8% were still on study.

What was learned with regard to subsequent treatments?

“A little more than half of the patients received subsequent lines of therapy [52.6%]; this was mainly chemotherapy [34.2%] and immunotherapy [13.2%],” Van Gorp noted. Other subsequent treatments included antibody-drug conjugate (7.9%), bevacizumab (7.9%), and a small molecule or TKI (5.3%). Patients received 1 (23.7%) or 2 (28.9%) lines of subsequent systemic treatment.

What was the toxicity profile of the tisotumab vedotin combination?

All patients experienced treatment-emergent AEs (TEAEs) and 92% of cases were grade 3 or higher. Serious TEAEs occurred in 66% of patients. Moreover, TEAEs led to dose reduction or interruption of tisotumab vedotin for 53% and 89% of patients, respectively; TEAEs led to discontinuation of tisotumab vedotin for 55% of patients and treatment discontinuation for 71% of patients. One fatal TEAE was reported in the form of a uterine infection deemed related to bevacizumab treatment.

The most common grade 3 or higher AEs were anemia (39.5%), thrombocytopenia (15.8%), fatigue (13.2%), neutropenia (13.2%), decreased neutrophil count (10.5%), hypertension (7.9%), decreased platelet count (7.9%), asthenia (5.3%), diarrhea (5.3%), keratitis (5.3%), ulcerative keratitis (5.3%), vaginal hemorrhage (5.3%), and weight decrease (5.3%).

AEs of special interest for tisotumab vedotin that were reported in at least 10% of patients included ocular AEs in the form of dry eye (grade 1, 32%; grade 2, 18%; grade 3, 5%), conjunctivitis (11%; 21%; 0%), keratitis (3%; 8%; 5%), and eye pruritus (11%; 3%; 0%); peripheral neuropathy AEs in the form of sensory neuropathy (16%; 40%; 0%), motor neuropathy (8%; 8%; 3%), and muscular weakness (5%; 5%; 0%); and bleeding AEs in the form of epistaxis (45%; 3%; 0%) and vaginal hemorrhage (11%; 8%; 0%).

“The safety profile of the tisotumab vedotin triplet/quadruplet was consistent with the known profile of each individual agent and toxicities were as expected,” Van Gorp concluded.

Disclosures: Dr Van Gorp disclosed receipt of consulting fees paid to institution from AbbVie, AstraZeneca, BeiGene, BioNTech, Cancer Communications and Consultancy Ltd, Daiichi Sankyo, Eisai, Genmab, GlaxoSmithKline, ImmunoGen, Incyte, Karyopharm, Lilly, MSD/Merck, OncXerna Therapeutics, Seagen, TORL BioTherapeutics, Tubulis, Verastem, and Zentalis. Research funding paid to the institution was provided by Amgen, AstraZeneca, and Roche. Honoraria paid to the institution was received by AbbVie, AstraZeneca, Eisai, GlaxoSmithKline, ImmunoGen, and MSD. Support for meetings and/or travel was provided by ImmunoGen, MSD, and PharmaMar. Van Gorp serves as chair of the Belgian and Luxembourg Gynaecological Oncology Group (unremunerated).

References

1. Van Gorp T, Vergote I, Randall L, et al. Tisotumab vedotin in combination with carboplatin and pembrolizumab with or without bevacizumab in first-line recurrent or metastatic cervical cancer: first disclosure of arm H from the ENGOT-cx8/GOG-3024/innovaTV 205 study. Presented at: 2026 SGO Annual Meeting; April 10-13, 2026; San Juan, Puerto Rico.
2. Vergote IV, Nieuwenhuysen EV, O’Cearbhaill RE, et al. Tisotumab vedotin in combination with carboplatin, pembrolizumab, or bevacizumab in recurrent or metastatic cervical cancer: results from the innovaTV 205/GOG-3024/ENGOT-cx8 study. J Clin Oncol. 2023;41(suppl 36):5536-5549. doi:10.1200/JCO.23.00720