Low-dose Pembrolizumab Plus Chemotherapy for the First-Line Treatment of Persistent, Recurrent, or Metastatic Cervical Cancer.

This is a phase II single-arm study of low-dose pembrolizumab plus chemotherapy in women aged 18 years or older with histologically confirmed persistent, recurrent, or metastatic cervical cancer who are ineligible for curative-intent treatment (surgery and/or radiation therapy) and who have not been previously treated with systemic chemotherapy, with the exception of chemotherapeutic agents used as radiosensitizers (cisplatin or carboplatin concurrent with radiation therapy). Participants must have measurable disease as defined by RECIST 1.1, as assessed by the local investigator/radiologist, and must provide a tumor tissue sample no older than 4 years for PD-L1 expression status determination. PD-L1 expression will be analyzed using the 22C3 antibody (Dako®) and classified according to the Composite Positive Score (CPS). Treatment will consist of pembrolizumab 100mg administered by intravenous infusion plus chemotherapy every 3 weeks. Chemotherapy may be paclitaxel 175 mg/m2 plus carboplatin AUC 5 or paclitaxel 175 mg/m2 plus cisplatin 50 mg/m2 for patients not previously exposed to cisplatin. Both carboplatin and cisplatin should be administered immediately after paclitaxel. All study treatments should be administered on Day 1 (D1) of each 3-week treatment cycle. All participants should receive premedication to prevent severe hypersensitivity reactions according to local practice. Premedication should be administered after the pembrolizumab infusion and before chemotherapy. During the treatment period, participants will have routine clinical visits for treatment administration, safety and well-being monitoring, and assessment of disease status changes. Primary safety assessments will include physical examinations, vital signs, electrocardiography (ECG), hematology and biochemistry tests, thyroid function tests, and urinalysis. At each visit, adverse events will be assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 1 5.0. Study treatment doses may be interrupted or reduced (applicable only to chemotherapy) or discontinued in case of severe adverse events. Imaging assessments will include computed tomography (CT) of the chest and magnetic resonance imaging (MRI) of the abdomen and pelvis. The first study imaging assessment will be performed at 9 weeks (63 days ± 7 days) from the date of Cycle 1 (C1) Day 1 infusion. Subsequent imaging should be performed every 9 weeks (63 days ± 7 days) until Week 54 and every 12 weeks (84 days ± 7 days) thereafter. Other imaging exams such as bone scintigraphy or brain imaging should be performed as clinically indicated. Participants may interrupt or discontinue pembrolizumab and continue in the study. Similarly, participants may interrupt or discontinue chemotherapy and continue treatment with pembrolizumab. Participants will receive study treatments until disease progression as defined by RECIST 1.1, unacceptable toxicities, intercurrent illness that precludes continued treatment, investigator's decision to withdraw the participant from treatment, withdrawal of consent, or administrative reasons requiring treatment discontinuation. Participants may receive up to 6 cycles of paclitaxel-platinum (carboplatin or cisplatin). Participants may receive a maximum of 35 administrations of pembrolizumab (approximately 2 years). In the case of complete response (CR), study treatment may be discontinued at the investigator's discretion after the CR has been confirmed by radiographic imaging and the participant has received at least 2 cycles of pembrolizumab and to have completed a minimum of 8 total treatment cycles (approximately 24 weeks). Participants who discontinue study treatment for reasons other than radiographic disease progression will be followed until documented disease progression by RECIST 1.1 criteria, initiation of new anticancer therapy, withdrawal of consent, loss to follow-up, or death. After discontinuation of study treatment, participants may initiate subsequent anticancer treatments at the discretion of the treating physician and in accordance with local standard of care. After verification of disease progression by RECIST 1.1 and/or initiation of subsequent oncological treatment, all participants will be followed up for overall survival (by telephone contact or in-person visits to the center) until withdrawal of consent, loss to follow-up, death, or until the study is completed or terminated early, whichever occurs first. Symptomatic improvement is a recognized clinical benefit. Participants will complete the EuroQol EQ-5D-5L, EORTC QLQ-C30, and EORTC QLQ-CX24 to assess quality of life. The study will begin when the first participant signs the Informed Consent Form and will end when the last participant completes the final study-related call or visit, withdraws from the study, or is lost to follow-up (i.e., the participant cannot be contacted by the investigator).