Pembrolizumab and Chemoradiation Treatment for Advanced Cervical Cancer

A Randomized Phase II Study of Chemoradiation and Pembrolizumab for Locally Advanced Cancer

The purpose of this study is to evaluate the safety and effectiveness of immunotherapy in combination with chemotherapy and radiation (chemoradiation) for the treatment of advanced cervical cancer. Pembrolizumab, a type of immunotherapy called a checkpoint inhibitor, will be administered after or during chemoradiation.

Primary: (1) To estimate the immunologic effects, as assessed in the tumor & PBMC, of both sequential and concurrent administration of pembrolizumab to CRT. Change between pre and post measurements of HPV E2, E7 specific CD8+ T cells, regulatory FoxP3+ T cells (Tregs) and the ratio of CD8+ T cells to Tregs are the immune measurements of primary interest. (2) To determine the safety of concurrent chemoradiation in combination with pembrolizumab for the treatment of locally advanced cervical cancer. Secondary: (1) To estimate rates of complete metabolic response on PET/CT imaging obtained 12 weeks after CRT.

(2) To estimate rates of distant metastasis as the first site of recurrence for patients.

(3) To estimate the influence of concurrent and consolidative MK-3475 on levels of plasminogen activator inhibitor-1 (PAI-1), a marker of immunosuppressive TGF-B.

(4) To estimate the influence of concurrent and consolidative MK-3475 on levels of IDO, an enzyme that depletes tryptophan, which is essential for T-cell function.

(5) To estimate the influence of concurrent and consolidative MK-3475 on levels of MHC class I (CD8+ T cell ligand) and MICA (NK ligand), as measured by MHC.

(6) To estimate the progression free survival (PFS) in subjects with locally advanced cervical cancer treated with sequential and concurrent administration of pembrolizumab in relation to CRT.

(7) To estimate the overall survival (OS) in subjects with locally advanced cervical cancer treated with sequential and concurrent administration of pembrolizumab in relation to CRT.

Inclusion Criteria:

• Confirmed cervical cancer.
• Must have adequate organ function.

Exclusion Criteria:

• Subject is pregnant.
• Recurrent cervical cancer.
• Distant metastases.
• Malignancy within the last 5 years; basal cell carcinoma or squamous cell carcinoma of the skin that has undergone potentially curative therapy is permissable.
• Subject has had prior radiation, chemotherapy, targeted therapy, or investigational therapy for cervical cancer.
• Subject has a immunodeficiency.
• Known history of HIV, Hepatitis B, Hepatitis C, TB, or inflammatory bowel disease.
• Hypersensitivity to pembrolizumab or similar drugs.
• Subject has an active autoimmune disease in the past 2 years.
• Known history of non-infectious pneumonitis.
• Subject has an active infection.
• Subject has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases are permissible. Talk to Study Contact for specifics.