Study of Chemoradiotherapy With or Without Pembrolizumab (MK-3475) For The Treatment of Locally Advanced Cervical Cancer (MK-3475-A18/KEYNOTE-A18/ENGOT-cx11/GOG-3047)

Completed · Phase 3 · Has a placebo group

Conditions studied: Uterine Cervical Neoplasms

In brief

The purpose of this study is to evaluate the efficacy and safety of pembrolizumab plus concurrent chemoradiotherapy compared to placebo plus concurrent chemoradiotherapy in participants with locally advanced cervical cancer. The primary hypotheses are that pembrolizumab plus concurrent chemoradiotherapy is superior to placebo plus concurrent chemoradiotherapy with respect to progression-free survival and overall survival. Once the study objectives have been met or the study has ended, participants will be discontinued from this study and will be enrolled in an extension study to continue protocol-defined assessments and treatment.

Key facts

Study ID

NCT04221945

Run by

Merck Sharp & Dohme LLC

People needed

1060

Starts

2020-05-12

Expected to finish

2026-01-26

Last updated by the study team

2026-02-20

Who can join

Age: 18 and older. Sex: female. Healthy volunteers: not accepted.

You may qualify if…

• Has high-risk locally advanced cervical cancer (LACC): The International Federation of Gynecology and Obstetrics (FIGO) 2014 Stage IB2-IIB (with node-positive disease) or FIGO 2014 Stages III-IVA
• Has histologically-confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix
• Has not previously received any definitive surgical, radiation, or systemic therapy for cervical cancer, including investigational agents, and is immunotherapy-naïve
• Female participants must not be pregnant or breastfeeding and agree to use highly effective contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab or placebo and 180 days following the end of chemoradiotherapy and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period.
• Female participants must abstain from breastfeeding during the study intervention period and for at least 120 days after the last dose of pembrolizumab or placebo and 180 days following the end of chemoradiotherapy
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the first dose of study treatment
• Has provided a tissue sample from a core incisional or excisional biopsy of a tumor lesion
• Has radiographically evaluable disease, either measurable or non-measurable per RECIST 1.1, as assessed by the local site investigator/radiology
• Has adequate organ function within 7 days prior to the start of study treatment.

You may not qualify if…

• Has excluded subtypes of LACC
• Has FIGO 2014 Stage IVB disease
• Has undergone a previous hysterectomy defined as removal of the entire uterus or will have a hysterectomy as part of their initial cervical cancer therapy
• Has bilateral hydronephrosis, unless at least one side has been stented or resolved by positioning of nephrostomy or considered mild and not clinically significant in the opinion of the investigator
• Has anatomy or tumor geometry or any other reason or contraindication that cannot be treated with intracavitary brachytherapy or a combination of intracavitary and interstitial brachytherapy
• Has received a live vaccine within 30 days prior to the first dose of study treatment
• Has received treatment with systemic immunostimulatory agents, colony stimulating factors, interferons, interleukins and vaccine combinations within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1
• Has received prior therapy with an anti-programmed cell death receptor 1 (PD-1), anti-programmed cell death receptor ligand 1 (PD-L1), or anti-programmed cell death receptor ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, CD137)
• Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to randomization
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to randomization
• Has any contraindication to the use of cisplatin
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in 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 treatment
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has severe hypersensitivity to pembrolizumab and/or any of its excipients
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has an active infection requiring systemic therapy
• Has a known history of Human Immunodeficiency Virus (HIV) infection
• Has a known history of Hepatitis B or known active Hepatitis C virus infection
• Has a history or current evidence of any condition, therapy, lab abnormality, or other circumstance that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results, and in the judgment of the investigator or Sponsor, would make the participant inappropriate for entry into this study
• Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
• Has had an allogenic tissue/solid organ transplant
• Has evidence of metastatic disease per RECIST 1.1 including lymph nodes above the first lumbar vertebra (L1) cephalad body, in the inguinal region

Where it is running

• UCLA Hematology/Oncology - Westwood (Building 200 Suite 120) ( Site 0027) — Los Angeles, California, United States
• Hoag Memorial Hospital Presbyterian ( Site 0038) — Newport Beach, California, United States
• UC Davis Comprehensive Cancer Center ( Site 0017) — Sacramento, California, United States
• University of Colorado Health Sciences Center and Hospital ( Site 0028) — Denver, Colorado, United States
• Smilow Cancer Center at Yale-New Haven ( Site 0023) — New Haven, Connecticut, United States
• AdventHealth Orlando-AdventHealth Medical Group Gynecological Oncology ( Site 0009) — Orlando, Florida, United States
• Parkview Research Center at Parkview Regional Medical Center ( Site 0026) — Fort Wayne, Indiana, United States
• University of Kentucky Markey Cancer Center ( Site 0015) — Lexington, Kentucky, United States
• Our Lady of the Lake Regional Medical Center. ( Site 0031) — Baton Rouge, Louisiana, United States
• Women's Cancer Care ( Site 0039) — Covington, Louisiana, United States
• Karmanos Cancer Institute ( Site 0018) — Detroit, Michigan, United States
• Minnesota Oncology Hematology, PA ( Site 8007) — Minneapolis, Minnesota, United States
• University of New Mexico Comprehensive Cancer Center-Clinical Research Office ( Site 0019) — Albuquerque, New Mexico, United States
• University of North Carolina at Chapel Hill ( Site 0025) — Chapel Hill, North Carolina, United States
• Sanford Bismarck Medical Center ( Site 0046) — Bismarck, North Dakota, United States
• The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C — Columbus, Ohio, United States
• Willamette Valley Cancer Institute and Research Center ( Site 8000) — Eugene, Oregon, United States
• Legacy Good Samaritan Medical Center ( Site 0013) — Portland, Oregon, United States
• Allegheny Health Network West Penn Hospital-Gynecologic Oncology ( Site 0030) — Pittsburgh, Pennsylvania, United States
• Hollings Cancer Center ( Site 0007) — Charleston, South Carolina, United States
• Sanford Gynecology Oncology ( Site 0003) — Sioux Falls, South Dakota, United States
• Texas Oncology-Austin Central ( Site 8006) — Austin, Texas, United States
• Texas Oncology-Fort Worth Cancer Center ( Site 8001) — Fort Worth, Texas, United States
• Texas Oncology-San Antonio Medical Center ( Site 8002) — San Antonio, Texas, United States
• HonorHealth Research Institute - Biltmore ( Site 8009) — Phoenix, Arizona, United States

Full record on ClinicalTrials.gov

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