This is a randomized, blinded, non-comparative, two-arm Phase 2 clinical trial to assess the efficacy and safety of AGEN2034 administered with placebo (Treatment Arm 1 - monotherapy) or with AGEN1884 (Treatment Arm 2 - combination therapy) for treatment of patients with advanced cervical cancer who relapsed or progressed after receiving first-line platinum-based chemotherapy. The study is not intended to compare the efficacy of the 2 experimental arms. Rather, the efficacy of each arm will be evaluated against its relevant historical controls as appropriate.
The primary objective is to assess the Objective Response Rate (ORR) to the treatment of AGEN2034 (anti PD-1) administered with placebo (Treatment Arm 1 - monotherapy), or with
AGEN1884 (anti-CTLA4) (Treatment Arm 2 - combination therapy), defined as
the binomial proportion of intent to treat (ITT) patients with best overall response
(BOR) of complete response (CR) or partial response (PR), in women with
recurrent/persistent/metastatic cervical cancer who have progressed following
first-line therapy. BOR will be determined by the Independent Radiology Review
Committee (IRRC), according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
Experimental: AGEN2034 + Placebo
AGEN2034 administered with placebo monotherapy: approximately 100 patients
Experimental: AGEN2034 + AGEN1884
AGEN2034 administered in combination with AGEN1884 (combination therapy): approximately 100 patients
Baptist MD Anderson Cancer Center
1.Voluntarily agree to participate by giving written informed consent. (Participation in pharmacogenomics testing is optional)
2.Be 18 years of age
a.Have (1) a histologically or cytologically confirmed diagnosis of squamous-cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix, and (2) metastatic, locally advanced, and/or unresectable disease at the time of enrollment. Histologic confirmation of the original primary tumor is required via pathology report.
Note: The following cervical tumors are not eligible: minimal deviation/adenoma malignum, gastric type adenocarcinoma, clear cell carcinoma, and mesonephric carcinoma.
b.Has cervical cancer and has relapsed after a platinum-based treatment (first line) regimen for advanced (recurrent, unresectable, or metastatic) disease;
Note: Patient receiving chemotherapy concurrently with primary radiation (e.g., weekly cisplatin) or patient receiving adjuvant chemotherapy following completion of radiation therapy (e.g., paclitaxel and carboplatin for 4 cycles) and progressed within 6 months after treatment completion will be eligible as this systemic therapy will be considered as first-line treatment.
Note: Patients must have at least one "target lesion" to be used to assess response, as defined by RECIST version 1.1. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented, or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
5.Have a life expectancy of at least 3 months and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6.Have adequate organ function as indicated by the following laboratory values:
a.Adequate hematological function defined by absolute neutrophil count (ANC) > 1.5 x 10^9/L, platelet count > 100 x 10^9/L, and hemoglobin >8 g/dL (without transfusions within 1 week of first dose).
b.Adequate hepatic function based by a total bilirubin level 1.5 the institutional upper limit of normal (IULN), aspartate aminotransferase (AST) level 2.5 x IULN, alanine aminotransferase (ALT) level 2.5 x IULN, and alkaline phosphatase 2.5 IULN and albumin 3.0 mg/dL.
c.Adequate renal function defined as calculated creatinine clearance >50 mL/min (creatinine clearance should be calculated using the Cockcroft-Gault Method).
d.Adequate coagulation defined by international normalized ratio (INR) or prothrombin time )
7.Have no history of prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous-cell carcinoma of the skin, and has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.
9.Patients must have a negative serum pregnancy test at screening (within 72 hours of first dose of study medication) if of childbearing potential or be of non-child bearing potential. Non-childbearing potential is defined as (by other than medical reasons):
a.45 years of age and has not had menses for greater than 1 year,
c.History of hysterectomy, oophorectomy or tubal ligation.
d.Definitive pelvic radiation for the treatment of cervical cancer.
10.If of childbearing potential, female patients must be willing to use 2 adequate barrier methods throughout the study, starting with
Secondary Trial ID Number