A Single-arm, Multicenter Clinical Study of Becotatug Vedotin Combined With Zimberelimab in the Treatment of Recurrent and Metastatic Cervical Cancer, Vulvar Cancer and Vaginal Cancer

Recurrent and metastatic cervical, vulvar, and vaginal cancers represent a significant clinical challenge, with limited treatment options and poor prognosis for patients who have failed standard therapies. These malignancies are often driven by persistent human papillomavirus (HPV) infection, leading to immunosuppression and tumor immune evasion. While immune checkpoint inhibitors, such as anti-PD-1 antibodies, have shown some efficacy, response rates remain suboptimal, highlighting the need for more effective combination strategies.

Becotatug vedotin is an antibody-drug conjugate (ADC) that selectively delivers a potent cytotoxic payload to tumor cells expressing specific antigens, thereby inducing targeted cell death. Zimberelimab is a monoclonal antibody targeting the PD-1 checkpoint receptor, which functions to reactivate the body's immune system to recognize and attack cancer cells. The combination of these two agents is hypothesized to exert a synergistic anti-tumor effect, by directly eliminating tumor cells while simultaneously overcoming immunosuppression in the tumor microenvironment.

This trial will evaluate the safety, tolerability, and preliminary efficacy of this novel combination regimen.

Inclusion criteria

A subject must meet all of the following criteria to be eligible for enrollment:

• The subject has a full understanding of the study, voluntarily agrees to participate, and signs the Informed Consent Form (ICF).
• Female, aged 18 to 75 years (inclusive).
• Life expectancy ≥ 3 months, as assessed by the investigator.
• Histologically confirmed squamous cell carcinoma of the cervix, vagina, or vulva.
• Have received at least one line of standard therapy, which must have included platinum-based chemotherapy and an immunotherapy agent; prior lines of therapy ≤ 4.
• ECOG performance status of 0 or 1.
• Presence of at least one measurable target lesion according to the RECIST 1.1 criteria.
• Adequate bone marrow function: absolute neutrophil count ≥ 1.5 × 10⁹/L, platelets ≥ 90 × 10⁹/L, hemoglobin ≥ 90 g/L.
• Adequate hepatic and renal function: serum creatinine ≤ 1.5 × upper limit of normal (ULN); AST and ALT ≤ 2.5 × ULN (≤ 5 × ULN for subjects with liver metastases); total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for subjects with liver metastases).
• Not pregnant or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 28 days prior to enrollment and agree to use an appropriate method of contraception from the time of signing the ICF until 6 months after the last study drug administration.
• Agrees to provide blood and histology samples.

Exclusion criteria

A subject will be ineligible for study enrollment if they meet any of the following criteria:

• Known hypersensitivity or allergic reaction to any study drug or its components.
• Use of a strong CYP3A4 inducer (e.g., anticonvulsants [phenytoin, phenobarbital, carbamazepine], rifampicin, rifabutin, St. John's Wort) within 2 weeks prior to the first dose of study medication; or use of a strong CYP3A4 inhibitor (e.g., grapefruit juice, clarithromycin, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, voriconazole) or a strong UGT1A1 inhibitor (e.g., atazanavir, gemfibrozil, indinavir) within 1 week prior to the first dose.
• Known central nervous system (CNS) metastases, meningeal metastases, spinal cord metastases or spinal cord compression.
• Currently having uncontrolled systemic diseases (e.g., progressive infection, uncontrolled hypertension, diabetes mellitus, etc.), or psychiatric disorders/social conditions that would limit the subject's ability to comply with study requirements or provide written informed consent.
• Radiologically confirmed intestinal obstruction; or a medical history of the following diseases: inflammatory bowel disease, extensive bowel resection (partial colectomy or extensive small bowel resection complicated by chronic diarrhea), Crohn's disease, ulcerative colitis.
• Active hepatitis B or hepatitis C infection (hepatitis B surface antigen positive with hepatitis B virus DNA > 1 × 10³ copies/mL; hepatitis C virus RNA > 1 × 10³ copies/mL).
• Human immunodeficiency virus (HIV) infection (positive HIV antibody test).
• Major surgery or severe trauma within 30 days prior to the first dose, or planned major surgery within 30 days after the first dose (as determined by the investigator).
• Pregnant or breastfeeding women; or women of childbearing potential who refuse to adopt effective contraceptive measures.
• Any other condition deemed unsuitable for study participation by the investigator.