Tisotumab Vedotin Enters a Phase 2 Test in Recurrent Vulvar Squamous Cell Carcinoma
A phase 2 study is preparing to test tisotumab vedotin in one of gynecologic oncology’s most difficult settings: recurrent or metastatic squamous cell carcinoma of the vulva. The trial is designed as an open-label, single-arm investigation with objective response rate as the main efficacy readout, a practical choice in a disease where treatment options remain limited and durable disease control is often elusive.
The study plans to enroll 28 participants and will open under the GOG Foundation umbrella at Atrium Health Levine Cancer Center in Charlotte, North Carolina. Treatment will be administered every 3 weeks, continuing until unacceptable toxicity, disease progression, or withdrawal at the request of the investigator or participant. For a malignancy that frequently presents late and can recur after local therapy, the design centers on whether a targeted antibody-drug conjugate can produce measurable tumor shrinkage in a population with few realistic curative options.
One sentence captures the entire clinical wager: can a drug built for tissue factor-directed delivery produce meaningful responses in vulvar cancer before the disease outruns local salvage?
Why This Tumor Type Needs a New Systemic Option
Recurrent vulvar cancer with squamous histology is a narrow but serious clinical niche. The protocol requires disease that is not amenable to curative therapy, including cases in which radiotherapy or exenterative surgery is no longer a realistic path. That eligibility threshold reflects the bedside reality of this cancer: once recurrence becomes metastatic or locally unresectable, management often shifts from cure to palliation, symptom control, and short-lived disease stabilization.
The biological rationale for tisotumab vedotin fits that unmet need. As an antibody-drug conjugate, it is designed to bind a tumor-associated target and deliver a cytotoxic payload directly into malignant cells. In squamous tumors, where tissue factor expression has made this agent attractive in other solid tumors, the strategy aims to increase antitumor activity while limiting systemic exposure compared with untargeted chemotherapy. In vulvar cancer, where evidence for later-line therapy remains sparse, even modest response signals could influence how oncologists sequence treatment after surgery, radiation, or prior systemic therapy.
Eligibility Criteria Define a Frail but Treatable Population
The trial allows adults with recurrent or metastatic vulvar cancer of squamous histology who have received no more than two prior systemic therapy regimens for recurrent or metastatic disease. Prior chemotherapy given in adjuvant or neoadjuvant settings, or alongside radiation, does not count as a separate regimen under the protocol. Participants also must have measurable disease by RECIST v1.1, with explicit size requirements for non-nodal and nodal lesions.
Laboratory thresholds are relatively conservative, which is important for a drug with known toxicity considerations. Participants need an estimated glomerular filtration rate of at least 50 mL/min/1.73 m2, adequate liver function, hemoglobin at least 9.0 g/dL, ANC of at least 1500/μL, and platelets at least 100 x 10^9/L. Performance status is restricted to ECOG 0 or 1, signaling that the study is targeting patients well enough to tolerate repeated infusions and ongoing toxicity surveillance.
A separate set of reproductive safeguards applies to participants of reproductive potential. Pregnancy testing is required, contraception must continue during treatment and for 6 months afterward, and breastfeeding or ova donation is prohibited over the same interval. Those requirements are standard for cytotoxic payloads delivered through antibody-drug conjugates, where fetal risk cannot be dismissed.
Safety Screening Suggests the Expected Toxicity Profile
The exclusion criteria reveal where investigators see the principal risks. Bleeding disorders, recent major bleeding, and recent trauma that could raise hemorrhagic risk are excluded, along with recent severe head trauma or intracranial surgery. Cardiovascular exclusions are also strict: unstable angina, recent myocardial infarction, severe heart failure, reduced ejection fraction, marked QT prolongation, and bundle branch block all remove a participant from eligibility.
Ocular toxicity deserves special attention. Participants with active ocular surface disease, cicatrizing conjunctivitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, mucus pemphigoid, or penetrating ocular transplants are excluded, while cataracts alone are not disqualifying. That pattern points to a class-effect concern seen with tisotumab vedotin: the eye is a vulnerable off-target site, and preexisting ocular injury can magnify harm. In practical terms, the screening framework tries to prevent corneal and conjunctival complications before they become treatment-limiting.
The protocol also bars several neurologic and oncologic conditions, including certain CNS vascular disorders and other active malignancies with more than negligible metastatic or mortality risk. Brain metastases are permitted only if local therapy has been completed, disease is stable, and perioperative steroid use has been tapered or completed, although stable chronic steroids are acceptable under the protocol.
A Small Cohort, a Narrow Endpoint, and a Long Timeline
This is not a large confirmatory trial. Enrollment is estimated at 28 participants, with study start projected for November 2026, primary completion in March 2029, and final completion in December 2029. The narrow size fits the rarity of the disease and the exploratory nature of the question. For a condition with limited evidence and small patient pools, a phase 2 signal can still matter if it changes the logic of later studies or expands systemic options beyond conventional chemotherapy.
Objective response rate is the central endpoint because response can be measured relatively cleanly in a single-arm study and may reveal whether the drug is producing meaningful antitumor activity at all. In a setting with recurrent or metastatic disease, tumor shrinkage can translate into symptom relief, improved local control, or a bridge to additional therapy. Whether those benefits emerge will depend not only on the drug’s antitumor potency but also on how often bleeding, ocular events, and other treatment-related toxicities force discontinuation.
The trial has no results posted yet, and no efficacy or safety data are available from this study record. What remains concrete is the clinical question embedded in the design: vulvar squamous cell carcinoma has long lacked a clearly effective later-line systemic therapy, and this phase 2 study will test whether tisotumab vedotin can fill part of that gap without introducing prohibitive toxicity.