Study of Cemiplimab in Adults With Cervical Cancer
Condition: Squamous Cell Carcinoma (SCC); Recurrent or Metastatic, Platinum-refractory Cervical Cancer
MeSH terms: Carcinoma; Uterine Cervical Neoplasms
Intervention: Cemiplimab; Investigator Choice (IC) Chemotherapy
Intervention description: Intravenous (IV) administration every 3 weeks (Q3W); IC chemotherapy options include:
Antifolate: Pemetrexed
Topoisomerase 1 inhibitor: Topotecan or Irinotecan
Nucleoside analogue: Gemcitabine
Vinca alkaloid: Vinorelbine
The only chemotherapy treatments allowed in the control arm are any of the 5 drugs that are listed as IC options above.
Intervention MeSH terms: Cemiplimab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 608.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective is to compare overall survival (OS) for patients with recurrent or
      metastatic cervical cancer who have histology of squamous cell carcinoma (SCC) and who have
      any eligible histology treated with either cemiplimab or investigator's choice (IC)
      chemotherapy.

      The secondary objectives performed among SCC patients and among all eligible histologies (SCC
      and adenocarcinoma/adenosquamous carcinoma (AC) are:

        -  To compare progression-free survival (PFS) of cemiplimab versus IC chemotherapy

        -  To compare objective response rate (ORR) (partial response [PR] + complete response
           [CR]) of cemiplimab versus IC chemotherapy per Response Evaluation Criteria in Solid
           Tumors (RECIST) 1.1

        -  To compare the duration of response (DOR) of cemiplimab versus IC chemotherapy

        -  To compare the safety profiles of cemiplimab versus IC chemotherapy by describing
           adverse events (AE)

        -  To compare quality of life (QOL) for patients treated with cemiplimab versus IC
           chemotherapy using the European Organization for Research and Treatment of Cancer
           Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
    

Eligibility criteria:

        The criteria listed below are not intended to contain all considerations relevant to a
        patient's potential participation in this clinical trial.

        Key Inclusion Criteria:

          1. Recurrent, persistent, and/or metastatic cervical cancer with squamous cell histology,
             for which there is not a curative-intent option (surgery or radiation therapy with or
             without chemotherapy).

               -  Acceptable histologies (squamous carcinoma, adenocarcinoma, and adenosquamous
                  carcinoma) as defined in the protocol

          2. Tumor progression or recurrence after treatment with platinum therapy (must have been
             used to treat metastatic, persistent, or recurrent cervical cancer)

          3. Patient must have measurable disease as defined by RECIST 1.1.

          4. Eastern Cooperative Oncology Group (ECOG) performance status ≤1

          5. ≥18 years old

          6. Adequate organ or bone marrow function

          7. Received prior bevacizumab therapy or had clinically documented reason why not
             administered

          8. Received prior paclitaxel therapy or had clinically documented reason why not
             administered

        Key Exclusion Criteria:

          1. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that
             required treatment with systemic immunosuppressive treatments

          2. Prior treatment with an agent that blocks the PD-1/PD-L1 pathway

          3. Prior treatment with other systemic immune-modulating agents that was

               1. within fewer than 4 weeks (28 days) of the enrollment date, or

               2. associated with irAEs of any grade within 90 days prior to enrollment, or

               3. associated with toxicity that resulted in discontinuation of the immune
                  modulating agent

          4. Active or untreated brain metastases

          5. Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within
             4 weeks prior to the first dose of study drug cemiplimab or IC chemo)

          6. Active infection requiring therapy

          7. History of pneumonitis within the last 5 years

          8. History of documented allergic reactions or acute hypersensitivity reaction attributed
             to antibody treatments

          9. Concurrent malignancy other than cervical cancer and/or history of malignancy other
             than cervical cancer within 3 years of date of first planned dose of study drug
             cemiplimab or IC chemo), except for tumors with negligible risk of metastasis or
             death, such as adequately treated cutaneous squamous cell carcinoma or basal cell
             carcinoma of the skin or ductal carcinoma in situ of the breast. Patients with
             hematologic malignancies (eg, chronic lymphocytic leukemia) are excluded.

        Note: Other protocol defined Inclusion/Exclusion apply