A Study to Compare Sacituzumab Tirumotecan (MK-2870) Monotherapy Versus Treatment of Physician's Choice as Second-line Treatment for Participants With Recurrent or Metastatic Cervical Cancer (MK-2870-020/TroFuse-020/Gog-3101/ENGOT-cx20)

Merck Sharp & Dohme (MSD)

Status and phase: Enrolling; Phase 3

Conditions: Cervical Cancer

Treatments: Drug: Topotecan; Biological: Sacituzumab Tirumotecan; Drug: Irinotecan; Drug: Vinorelbine; Drug: Gemcitabine; Biological: Tisotumab Vedotin; Drug: Pemetrexed

Study type: Interventional

Funder types: Other; NETWORK; Industry

Identifiers

NCT06459180

GOG-3101 (Other Identifier)

TroFuse-020 (Other Identifier)

2023-508323-12-00 (Registry Identifier)

jRCT2031240201 (Registry Identifier)

ENGOT-cx20 (Other Identifier)

U1111-1298-0563 (Other Identifier)

2870-020

MK-2870-020 (Other Identifier)

Details and patient eligibility

About

This study will have two phases: a sacituzumab tirumotecan safety run-in and a Phase 3 portion. The safety run-in phase will be used to evaluate the efficacy and safety of sacituzumab tirumotecan at the dose for evaluation in the Phase 3 portion. The purpose of this study is to compare the efficacy and safety of sacituzumab tirumotecan versus treatment of physician's choice as second-line treatment for participants with recurrent or metastatic cervical cancer in the Phase 3 portion.

The primary study hypotheses are that, in the Phase 3 portion, sacituzumab tirumotecan results in a superior overall survival compared to TPC in participants with high trophoblast cell surface antigen 2 (TROP2) expression level and in all participants.

Enrollment: 686 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Has histologically-confirmed diagnosis of squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix
• Must have recurrent or metastatic cervical cancer that has progressed on or after treatment with 1 prior line of systemic platinum doublet chemotherapy (with or without bevacizumab) AND must have received anti-PD-1/anti-PD-L1 therapy as part of prior cervical cancer regimens
• Has measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, as assessed by the investigator. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions
• Is assigned female sex at birth, at least 18 years of age at the time of providing the informed consent
• Has ECOG performance status of 0 or 1 within 7 days before allocation for the Sacituzumab Tirumotecan Run-in or within 7 days before randomization for the Phase 3 portion
• Has provided tumor tissue (most recent sample is preferred) from a core or excisional biopsy of a tumor lesion not previously irradiated
• HIV-infected participants must have well controlled human immunodeficiency virus (HIV) on antiretroviral therapy (ART)
• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to allocation (Sacituzumab Tirumotecan Run-in) or randomization (Phase 3 portion)
• Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
• Has adequate organ function

Exclusion criteria

• Has Grade ≥2 peripheral neuropathy
• Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
• Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea)
• Has uncontrolled, significant cardiovascular disease or cerebrovascular disease.
• Received prior systemic anticancer therapy
• Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed
• Has other histological subtypes of cervical cancer apart from squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma (eg, carcinosarcoma), or has a diagnosis of nonepithelial cancer (eg, sarcoma, neuroendocrine tumors) of the cervix.
• Known additional malignancy that is progressing or has required active treatment within the past 3 years
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Active infection requiring systemic therapy
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• Concurrent active Hepatitis B and active Hepatitis C virus infection
• Severe hypersensitivity (≥Grade 3) to sacituzumab tirumotecan or treatment of physician's choice (TPC) and/or any of their excipients, or other biologic therapy
• Participants who have not adequately recovered from major surgery or have ongoing surgical complications
• Has a history of (noninfectious) pneumonitis/ILD that required steroids or has current pneumonitis/ILD

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

686 participants in 2 patient groups

Sacituzumab Tirumotecan

Experimental group

Description:

Participants will receive 4 mg/kg of sacituzumab tirumotecan once every 2 weeks (Q2W) via intravenous (IV) infusion until progressive disease or discontinuation.

Treatment:

Biological: Sacituzumab Tirumotecan

Treatment of Physician's Choice (TPC)

Active Comparator group

Description:

At the physician's discretion, participants will receive 500 mg/m\^2 of pemetrexed on day 1 of every 3-week cycle via IV infusion OR 2 mg/kg of tisotumab vedotin on day 1 of every 3-week cycle via IV infusion OR 1 mg/m\^2 (or 1.25 mg/m\^2 if tolerating well) topotecan on days 1, 2, 3, 4, and 5 of every 3-week cycle via IV infusion OR 30 mg/m\^2 of vinorelbine on days 1 and 8 of every 3-week cycle via IV infusion OR 1000 mg/m\^2 of gemcitabine on day 1 and 8 of every 3-week cycle via IV infusion OR 100 mg/m\^2 (or 125 mg/m\^2 if tolerating well) of irinotecan on days 1, 8, 15, and 22 of every 6 week cycle via IV infusion, until progressive disease or discontinuation.

Treatment:

Drug: Pemetrexed

Biological: Tisotumab Vedotin

Drug: Gemcitabine

Drug: Vinorelbine

Drug: Irinotecan

Drug: Topotecan