This study is currently recruiting participants.
This is a Phase 2 study of PRGN-2009 in patients with recurrent or metastatic cervical cancer who are pembrolizumab resistant. Patients meeting all eligibility criteria who consent to participate in the study will receive PRGN-2009 (5 x 10^11 PU, subcutaneous injection) every 3 weeks for three administrations, thereafter every 6 weeks, plus pembrolizumab (400 mg IV) every 6 weeks. Subjects will receive study treatment until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or study closure.
INCLUSION CRITERIA:
1. Age 18 years and older.
2. Recurrent or metastatic cervical cancer (histologically or cytologically confirmed)
3. 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 the study.
4. Subjects must have histologically or cytologically confirmed HPV positive disease confirmed by using at least one of the following methods:
-- Medical history of any positive HPV result using an FDA approved assay
-- Any level of p16 overexpression on a tumor biopsy will be accepted for eligibility
-- Positive HPV result using FDA approved assay if the disease is amenable to a cervical or vault smear
5. Provide a newly obtained tumor tissue sample, if clinically feasible. If a recent biopsy is not available, an archival FFPE sample should be provided. Biopsy samples must be from a site not previously irradiated.
6. 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. Note: Previously irradiated lesions cannot be considered target lesions.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
8. Life expectancy >= 12 weeks from the time of enrollment.
9. 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 >= 8.5 g/dL (patients must not have had transfusion or erythropoietin [EPO] within 4 weeks).
-- 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. GFR can also be used in place of creatinine or 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, or if unless patient is receiving anticoagulant therapy, PT or a PTT is within therapeutic range of intended use of anticoagulants.
10. Patient does not require supplemental oxygen or mechanical ventilation and has an oxygen saturation of >= 92% or higher on room air.
11. Negative serum pregnancy test. Persons of child-bearing potential (POCBP) must agree to use adequate contraception prior to study entry and for at least 6 months following completion of study treatment.
12. All patients must have the ability to understand and willingness to sign a written informed consent.
EXCLUSION CRITERIA:
Patients will be excluded from entry to the study if any of the following criteria are met:
1. Prior chemotherapy targeted small molecule therapy, or radiation therapy with the intent to treat 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.
-- Radiation therapy in a palliative setting or local radiation (ex. radiation therapy for one or more lesions for symptom control in subjects with multiple lesions provided that not all lesions are irradiated) is allowed prior to treatment
2. 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.
3. Active hepatitis B (positive HBsAg test) or hepatitis C (positive HCV RTPCR) infection based on testing performed within 30 days of enrollment.
4. History of non-infectious pneumonitis or interstitial lung disease.
5. Patients with a history of endocrine autoimmune disease, with the exception of:
a. History of Graves disease, now euthyroid for > 4 weeks
b. Hypothyroidism managed by thyroid replacement
6. Has received a live vaccine within 30 days prior to the first dose of study drug.
7. 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.
8. Symptomatic central (CNS) metastases must have been treated, be asymptomatic for >= 14 days, and meet the following at the time of enrollment:
-- No concurrent treatment for CNS disease (e.g., surgery, radiation, corticosteroids >10 mg prednisone/day or equivalent)
-- No concurrent leptomeningeal disease or cord.
9. Has severe hypersensitivity (>=Grade 3) to pembrolizumab and/or any of its excipients.
10. Known history of active tuberculosis (TB, Bacillus tuberculosis).
11. Pregnant and lactating women are excluded from this study.
12. Patients with a history of solid organ transplant.
13. Patients currently participating in a study of an investigational agent or have used an investigational device within 4 weeks prior to the first dose of study treatment.
14. Patients, who in the opinion of the investigator, may not be able to comply with the monitoring requirements of the study.
15. Patients with uncontrolled serious infection, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, poorly controlled pulmonary disease, psychiatric illness/social situations serious illness, or any other medical condition, which in the investigator s opinion would interfere with the patient s participation in the study, or with the interpretation of the results.