Pembrolizumab plus Lenvatinib in vulvar cancer patients: The prospective, multi-cohorts and multicentre, phase 2 MITO VULVA-01 study.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Trial duration

12 Feb 2026 → ongoing

Decision date (initial)

2025-09-12

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

MSD Italia S.r.l.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To determine the activity (as assessed by objective response rate) and safety of Pembrolizumab plus Lenvatinib in vulvar cancer patients for each study cohorts.

Secondary objectives 4

1. Description of progression-free survival (PFS) in the different single cohorts
2. Description of overall survival (OS) in each single cohort
3. Description of overall safety of pembrolizumab and lenvatinib in patients who receive more than 4 cycles of treatment
4. Description of response rate, progression-free survival (PFS) and overall survival (OS) according to the biomarkers’ based subpopulations and PDL1 expression

Conditions and MedDRA coding

vulvar cancer

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Signed informed consent prior to any study specific procedures
2. Female, age ≥ 18 years at time of signing informed consent
3. Patients with histologically or cytologically confirmed unresectable squamous cell carcinoma, adenocarcinoma and mixed histology (adenosquamous) of the vulva, defined as: a. T2 or T3 primary tumors (N0-3, M0) not amenable to surgical resection by standard radical vulvectomy (Cohort A) OR b. patients with recurrent or de novo metastatic chemotherapy-naive vulvar squamous cell carcinoma, adenocarcinoma and mixed histology (adenosquamous) of the vulva, (Cohort B) OR c. patients with recurrent squamous cell carcinoma of the vulva after primary chemoradiation or patients with metastatic squamous cell carcinoma, adenocarcinoma and mixed histology (adenosquamous) of the vulva in progression to a chemotherapy based treatment (Cohort C)
4. At least 1 measurable target lesion according to RECIST 1.1
5. Patients must have a life expectancy ≥ 16 weeks
6. ECOG performance status of 0 to 1
7. Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤140/90 mmHg at Screening and no change in antihypertensive medications within 1 week before the Cycle 1/Day 1.
8. Patient must provide formalin fixed paraffin embedded (FFPE) archival tumor sample, from primary surgery or from biopsy of primary tumor or metastases. Samples must be collected before any treatment (chemotherapy-naïve patients). A centralized quality control analysis of samples will be performed before patient’s enrollment. Only patients with adequate tumor sample for will be enrolled.
9. Patient must be able to take oral medications
10. Patients must have normal organ and bone marrow function measured as defined below: i. Haemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days ii. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L iii. Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be ≤ 5x ULN iv. Patients must have creatinine clearance estimated of ≥51 mL/min using the Cockcroft-Gault equation or based on a 24 hour urine test: Estimated creatinine clearance = (140-age [years]) x weight (kg)(x F)a serum creatinine (mg/dL) x 72 (a where F=0.85 for females)
11. INR or PT aPTT/PTT ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
12. Patient is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: a. Is not a Women of Childbearing Potential (WOCBP) b. Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), as described in Appendix 1 during the intervention period and for at least 4 monts post pembrolizumab or 30 days post lenvatinib, whichever occurs last. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
13. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention. Note If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive
14. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.

Exclusion criteria 31

1. Patients with vulvar melanomas, sarcomas, vulvar Paget's disease, or basal cell carcinoma
2. Patients diagnosed with early-stage vulvar cancer that, according to the Investigator, can be treated with upfront curative surgery
3. Patients who have received any systemic anticancer therapy for vulvar cancer, anti-VEGF therapy, or any systemic investigational anticancer agent including radiotherapy (Cohort A and B); Patients who have received any further systemic therapy for advanced disease after progression to a first-line platinum-based chemotherapy (Cohort C)
4. Received a live vaccine or live attenuated within 30 days of planned start of study treatment (Cycle 1/Day 1). Note: The killed virus vaccines (ie seasonal influenza vaccines for injection are allowed)
5. Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula
6. Active infection (any infection requiring systemic treatment)
7. Subjects known to be positive for Human Immunodeficiency Virus (HIV)
8. Patients with known active hepatitis (i.e. Hepatitis B or C) i. Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible. ii. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA
9. Subjects with a diagnosis of immunodeficiency or who are receiving systemic steroid therapy (dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medications
10. Active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
11. Patients unable to swallow orally administered medication
12. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment;
13. Major surgery within 3 weeks of starting study treatment and patients must have recovered from any effects of major surgery. Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility;
14. Breast feeding women;
15. Known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, (i.e. without evidence of progression) for at least 4 weeks by repeat imaging (Note: The repeat imaging should be performed during study Screening.), clinically stable, and without requirement of steroid treatment for at least 14 days before the first dose of study intervention; Note: Participants with known untreated, asymptomatic brain metastases (ie, no neurological symptoms, no requirement for corticosteroids, no or minimal surrounding edema, and no lesion >1.5 cm) may participate but will require regular imaging of the brain as a site of disease;
16. Other malignancy unless curatively treated with no evidence of disease for ≥5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS); Stage 1, grade 1 endometrial carcinoma
17. Prolongation of QTcF interval to ≥480 msec
18. LVEF below of the institutional (or local laboratory), normal range, as determined, by MUGA or ECHO
19. Participation in another clinical study with an investigational product during the last 3 months
20. Subjects who have not recovered adequately from any toxicity from other anti-cancer treatment regimens and/or complications from major surgery prior to starting therapy. Note: Withhold lenvatinib for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing
21. Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, cerebro vascular accident/stroke within 12 months of the first dose of study drug, or cardiac arrhythmia associated with hemodynamic instability. Medically controlled arrhytmia would be permitted
22. Bleeding or thrombotic disorders or subjects at risk for severe hemorrhage
23. Radiographic evidence of tumor invasion/infiltration of major blood vessels (e.g. carotid artery) or intratumoral cavitation. Note: The degree of major blood vessel should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy
24. History of arterial tromboembolism within 12 months of start the study
25. Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug
26. Has urine protein ≥1 g/24 hours. Note: Participants with proteinuria ≥2+ (≥100 mg/dL) on urine dipstick testing (urinalysis) will undergo 24-hour urine collection for quantitative assessment of proteinuria
27. GI malabsorption or any other condition that might affect the absorption of Lenvatinib
28. An allogenic tissue/solid organ transplant
29. History of (non infectious) pneumonitis/interstizial lung disease that require steroids or current pneumonitis/ interstitial lung disease
30. Known psychiatric disorder or substance abuse that would interfere with participant ability to cooperate with the requirement of the study
31. Has received prior therapy with an anti-PD1, anti PD-L1 or anti PD-L2 agent or anti PD- L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Objective response rate (ORR) defined as a complete response (CR) or partial response (PR) by the Investigator using RECIST 1.1 criteria, in each single cohort (ORR will be evaluated after 4 cycles in Cohort A patients and on the whole treatment period in Cohort B and C patients)
2. Safety profile of Pembrolizumab plus Lenvatinib according to CTCAE (version 5.0) and PRO-CTCAE questionnaire in the overall study population

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Sponsor organisation

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Address

Via Mariano Semmola 52

City

Naples

Postcode

80131

Country

Italy

Scientific contact point

Organisation

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Contact name

Sandro Pignata

Public contact point

Organisation

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Contact name

Clorinda Schettino

Third parties 2

Locations

1 EU/EEA country · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications