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Induction pembrolizumab with carboplatin/paclitaxel before chemoradiation and pembrolizumab maintenance for high‑risk locally advanced cervical cancer

NRG-GY037: A Phase III Study of Induction Pembrolizumab and Chemotherapy Followed by Chemoradiation and Pembrolizumab Versus Chemoradiation and Pembrolizumab Both Followed by Pembrolizumab for High Risk Locally Advanced Cervical Cancer

Phase 3 Interventional National Cancer Institute (NCI) · NCT07061977

This phase III trial tests whether giving pembrolizumab with carboplatin and paclitaxel before chemoradiation, then continuing pembrolizumab as maintenance, helps people with locally advanced high‑risk cervical cancer stay free of progression longer than starting pembrolizumab during chemoradiation.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment336 (estimated)
Ages18 Years and up
SexFemale
SponsorNational Cancer Institute (NCI) NIH
Drugs / interventionsimmunotherapy, radiation, prednisone, pembrolizumab, chemotherapy
Locations239 sites (Birmingham, Alabama and 238 other locations)
Trial IDNCT07061977 on ClinicalTrials.gov

What this trial studies

This randomized phase III trial compares two approaches for locally advanced cervical cancer: induction pembrolizumab plus carboplatin/paclitaxel followed by concurrent chemoradiation with pembrolizumab and pembrolizumab maintenance versus standard concurrent chemoradiation with pembrolizumab and pembrolizumab maintenance. The primary endpoint is progression‑free survival, with secondary endpoints including overall survival, toxicity (CTCAE v5.0), treatment timing and completion, and biomarker correlations. The study includes integrated biomarker studies such as baseline PD‑L1, serial circulating tumor DNA, T‑cell receptor repertoire dynamics, allostatic load correlations, and radiotherapy quality review aided by AI. Eligible patients are newly diagnosed with locally advanced squamous, adeno, or adenosquamous cervical cancer without high para‑aortic nodal metastasis and must be able to receive chemotherapy, immunotherapy, and radiation including brachytherapy.

Who should consider this trial

Good fit: Ideal candidates are people with newly diagnosed locally advanced cervical cancer (FIGO III–IVA or T3/T4 disease, including regional nodal involvement up to T12/L1) of squamous, adenocarcinoma, or adenosquamous histology who can tolerate combined chemo, immunotherapy, and radiation.

Not a fit: Patients with early‑stage disease, para‑aortic lymph node metastases above the T12/L1 interspace, prior definitive treatment for cervical cancer, or major comorbidities precluding chemo, immunotherapy, or radiation are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could extend the time patients live without disease progression and potentially improve overall survival by treating systemic disease earlier.

How similar studies have performed: PD‑1 inhibitors like pembrolizumab have shown activity in recurrent/metastatic cervical cancer and combinations with radiation are under study, but using induction pembrolizumab plus chemotherapy before chemoradiation is a relatively novel strategy with limited phase III precedent.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Patients must have pathologically confirmed newly diagnosed cervical cancer. Eligible pathologic types: squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma
* Patients must have locally advanced cervical cancer (LACC) with T3 or T4 disease with or without lymph node involvement:

  * IIIA (T3aN0M0)
  * IIIB (T3bN0M0)
  * IIIC1(T3aN1M0, T3bN1M0)
  * IIIC2 (T3aN2M0, T3bN2M0)
  * IVA (T4aN0M0, T4aN1M0, T4aN2M0) No prior hysterectomy defined as removal of the entire uterus.
  * NOTE: prior partial/subtotal hysterectomy for reasons other than cervical cancer are eligible to participate in the study. No plan to perform a hysterectomy as part of initial cervical cancer therapy.

No paraaortic lymph node (PALN) metastases above the T12/L1 interspace.

* Note: Nodal status can be confirmed by imaging (CT, MRI, or PET/CT), fine needle aspirate/core biopsy, extra peritoneal biopsy, laparoscopic biopsy, or lymphadenectomy.

Radiologic definition of lymph node staging:

* N1:

  * One or more pelvic lymph nodes with short axis diameter of ≥ 15 mm (axial plane) by CT or MRI, and/or
  * One or more pelvic lymph nodes with short axis diameter of ≥ 10 mm and standardized uptake value maximum (SUVmax) ≥ 2.5 by fludeoxyglucose (FDG)-PET
* N2:

  * One or more para-aortic lymph node with short axis diameter of ≥ 15 mm (axial plane) by CT or MRI, and/or
  * One or more para-aortic lymph node with short axis diameter of ≥ 10 mm and SUVmax ≥ 2.5 by FDG-PET

    * No prior definitive surgical, radiation, or systemic therapy for cervical cancer
    * No prior immunotherapy
    * No prior pelvic radiation therapy for any disease
    * Age ≥ 18
    * Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
    * Not pregnant and not nursing
    * Absolute neutrophil count (ANC) ≥ 1,500 cells/mm\^3
    * Platelets ≥ 100,000 cells/mm\^3
    * Hemoglobin ≥ 8 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobulin \[Hgb\] ≥ 8 g/dl is acceptable)
    * Creatinine clearance (CrCL) of ≥ 50 mL/min by the Cockcroft-Gault formula
    * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x institutional ULN may be enrolled)
    * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x institutional ULN
    * Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
    * No active infection requiring parenteral antibiotics
    * No live vaccine within 30 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacille Calmette Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines are live attenuated vaccines and are not allowed
    * No 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 registration
    * No active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
    * No history of (non-infectious) pneumonitis that required steroids, or current pneumonitis
    * No history of allergic reaction to the study agent(s) or compounds of similar chemical or biologic composition to the study agent(s) (or any of its excipients)

Where this trial is running

Birmingham, Alabama and 238 other locations

+189 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Locally Advanced Cervical AdenocarcinomaLocally Advanced Cervical Adenosquamous CarcinomaLocally Advanced Cervical Squamous Cell CarcinomaStage IIIA Cervical Cancer FIGO 2018Stage IIIB Cervical Cancer FIGO 2018Stage IIIC1 Cervical Cancer FIGO 2018Stage IIIC2 Cervical Cancer FIGO 2018Stage IVA Cervical Cancer FIGO 2018
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.