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Protocol Details

A Randomized, Open Label, Two-Arm, Multicenter Phase 2 Study to Evaluate Efficacy and Safety of PRGN-2009 in Combination with Pembrolizumab Versus Pembrolizumab in Patients with Recurrent or Metastatic Cervical Cancer

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Recruitment has not started
Gender: Female
Min Age: 18 Years
Max Age: 120 Years

Referral Letter Required


Population Exclusion(s)

Pregnant Women;


Human Papilloma Virus;
Cervical Cancer;
Therapeutic Vaccine;
Cervix Cancer;
Resistance to Checkpoint Inhibitors

Recruitment Keyword(s)



Uterine Neoplasms;
Genital Neoplasms, Female;
Urogenital Neoplasms;
Neoplasms by Site;
Uterine Cervical Diseases;
Uterine Diseases;
Genital Diseases, Female;
Female Urogenital Diseases;
Female Urogenital Diseases and Pregnancy Complications;
Urogenital Diseases;
Genital Diseases;
Uterine Cervical Neoplasms;
Antineoplastic Agents, Immunological;
Antineoplastic Agents;
Immune checkpoint Inhibitors;
Molecular Mechanisms of Pharmacological Action;

Investigational Drug(s)

MK-3475 (Pembrolizumab)
PRGN-2009 (gorilla-derived adenovirus-expressing HPV-16/18 E6/E7 vaccine)

Investigational Device(s)



Biological/Vaccine: PRGN-2009
Drug: Pembrolizumab

Supporting Site

National Cancer Institute


Cervical cancer is the 4th leading cause of death in women worldwide. More than 90% of women survive more than 5 years when the disease is treated in its earliest stages. But if the disease returns or spreads, only about 17% of women survive 5 years. Better treatments are needed.


To test a new drug (PRGN-2009) combined with pembrolizumab vs pembrolizumab alone in women with cervical cancer.


Women aged 18 years or older with cervical cancer that came back or spread after treatment with pembrolizumab.


Participants will be screened. They will have blood tests, chest x-rays, imaging scans, and tests of heart function. They will have a biopsy: A tissue sample will be taken from their tumor.

Pembrolizumab is given through a tube attached to a needle inserted into a vein. All participants will receive this drug every 6 weeks.

PRGN-2009 is injected under the skin. Half of participants will get both drugs. The first 3 doses of PRGN-2009 will be given at 3-week intervals; after that, participants will get the injections every 6 weeks.

All participants will have regular clinic visits. Blood tests, biopsies, and imaging scans will be repeated. They may also give nasal swabs, skin swabs, urine, and stool samples.

If their disease progresses, participants who were not getting PRGN-2009 may begin taking that study drug.

Participants may remain in the study as long as the treatment is helping them. If they stop taking the study drugs, follow-up visits will continue every 12 weeks for up to 5 years. These visits may be in person or by phone.

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-Age 18 years and older.

-Recurrent or metastatic cervical cancer (histologically or cytologically confirmed) that meets the criteria of resistant to pembrolizumab

-Must have been treated with pembrolizumab, either as monotherapy or in combination, for at least 6 weeks

--Patients that discontinued pembrolizumab treatment due to an adverse event or have an ongoing adverse event (> Grade 2) due to pembrolizumab treatment are ineligible for this study.

-Patients must have received no more than two prior systemic regimens in the recurrent or metastatic setting.

-Tumors are positive for PD-L1 and HPV16/18:

--Expression of PD-L1 combined positive score must be >= 1 in newly obtained biopsy*

--HPV16 or HPV18 detected using FDA approved test of newly obtained biopsy*, if no prior testing of the tumor has been performed

*If it is not possible to obtain a fresh biopsy, a recently obtained archival tumor sample of a non-irradiated lesion is acceptable.

-Measurable disease that can be accurately measured by RECIST v1.1 criteria in at least one dimension as >=1.0 cm or 1.5 cm for lymph nodes. Previously irradiated lesions cannot be considered target lesions.

-Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

-Life expectancy >= 12 weeks from the time of enrollment.

-Must have adequate organ function, as determined by the following values:

--Hematological lab values determined within 14 days of treatment:

---Absolute neutrophil count (ANC) >= 1,500 /microL

---Platelets >=100,000 / microL

---Hemoglobin >= 9 g/dL or >=5.6 mmol/L without transfusion or erythropoietin (EPO) dependency

--Serum creatinine (Cr) < 2.0 x upper limit of normal (ULN) or calculated or measured creatinine clearance (absolute value) of >= 40 mL/minute or Cr. Glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl).

--Serum total bilirubin <= 2.0 x ULN or direct bilirubin <= 1.0 x ULN for patients with elevated total bilirubin.

--Alanine aminotransferase (ALT, SGPT) and aspartate aminotransferase (AST, SGOT) < 2.5 x ULN (or < 5 x ULN for patients with liver metastases).

--Ejection fraction measured by echocardiogram (ECHO) or multigated acquisition scan (MUGA) > 45%.

--International normalized ratio (INR) OR prothrombin time (PT) and activated partial thromboplastin time (aPTT) <= 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or a PTT is within therapeutic range of intended use of anticoagulants.

--Thyroid Stimulating Hormone <= 1.0 x ULN.

-Patient does not require supplemental oxygen or mechanical ventilation and has an oxygen saturation of >= 92% or higher on room air.

-Negative serum pregnancy test. Women of child-bearing potential (WOCBP) must agree to use adequate contraception prior to study entry and for at least 6 months following completion of study treatment. Acceptable effective methods of contraception (see list, below).

Highly Effective Contraceptive Methods:

--Failure rate of <1% per year when used consistently and correctly*:

---Implantable progestogen-only hormonal contraception associated with inhibition of ovulation

---Intrauterine device (IUD)

---Intrauterine hormone-releasing system (IUS)

---Bilateral tubal occlusion

---Vasectomized partner:

A vasectomized partner is a highly effective contraception method provided that the partner is the sole male sexual partner of the WOCBP and the absence of sperm has been confirmed. If not, an additional highly effective method of contraception should be used.

---Sexual abstinence:

Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drug. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the patient.

--Failure rate of 6-12% per year when used consistently and correctly*:

---Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation




---Progestogen-only hormonal contraception associated with inhibition of ovulation


-All patients must have the ability to understand and willingness to sign a written informed consent.


-Prior chemotherapy targeted small molecule therapy, or radiation therapy within 14 days of start of treatment; an antineoplastic monoclonal antibody within prior 4 weeks, or has not recovered from (i.e., <= Grade 1) adverse events caused by prior treatment.

-Patients with a diagnosis of immunodeficiency, patients with active autoimmune disease requiring systemic immunosuppressive therapy (i.e., > 10 mg of prednisone daily or equivalent), or patients who have received any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Note: patients with HIV are eligible if they have sufficient disease control, in the opinion of the investigator.

-Active hepatitis B or C infection based on testing performed within 30 days of enrollment.

-History of pneumonitis.

-Has received a live vaccine within 30 days prior to the first dose of study drug.

-Ongoing uncontrolled serious infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, poorly controlled pulmonary disease, or psychiatric illness/social situations that would limit compliance with study requirements.

-Patients with presence of other active malignancy within 1 year prior to study entry; patients with adequately resected basal or squamous cell carcinoma of the skin may enroll irrespective of the time of diagnosis.

-Known central nervous system (CNS) disease.

-Has severe hypersensitivity (>=Grade 3) to pembrolizumab and/or any of its excipients.

-Known history of active tuberculosis (TB, Bacillus tuberculosis).

-Pregnant and lactating women are excluded from this study.

-Patients with a history of solid organ transplant.

-Patients currently participating in or have participated in a study of an investigational agent or have used an investigational device within 4 weeks prior to the first dose of study treatment.

-Patients, who in the opinion of the investigator, may not be able to comply with the monitoring requirements of the study.

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Not Provided

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Principal Investigator

Referral Contact

For more information:

James L. Gulley, M.D.
National Cancer Institute (NCI)
(301) 480-7164

NCI Medical Oncology Referral Office
National Cancer Institute (NCI)

(888) 624-1937

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office

Clinical Trials Number:


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