Pembrolizumab Plus Bevacizumab Combination Therapy in Patients With Metastatic Cervical Cancer: Registry Study of 12‑Month Progression‑Free Survival

The primary objective is to assess 12‑month progression‑free survival and compare it with historical data from the KEYNOTE‑826 trial.

Secondary objectives are to:

• evaluate 12‑ and 24‑month progression‑free survival
• assess overall survival
• determine objective response rate
• measure duration of response
• describe treatment‑related immune‑related adverse events
• characterize patient quality of life over time

The trial enrolled female patients diagnosed with metastatic cervical cancer. The sponsor did not provide the total number of participants, and specific age limits were not disclosed. Eligibility required enrollment in an observation cohort of individuals with persistent, recurrent, or metastatic disease initiating or receiving a pembrolizumab‑based regimen, or inclusion in an early discontinuation cohort after prior participation in the observation group and meeting criteria for treatment cessation (e.g., confirmed complete or partial response after ≥8 cycles of pembrolizumab, grade ≥ 3 immune‑related toxicity, or patient‑driven discontinuation). General health status was limited to patients deemed suitable for pembrolizumab therapy, with no additional lifestyle or habit requirements reported. No further inclusion or exclusion details were provided.

The PROTECx study is a low‑intervention, phase 6 registry that prospectively evaluates outcomes of pembrolizumab‑containing regimens, with or without bevacizumab, in patients with metastatic cervical cancer. The design comprises two pre‑specified cohorts: an observation cohort of individuals initiating or receiving pembrolizumab‑based therapy, and an early‑discontinuation cohort defined by confirmed complete or partial response after ≥8 cycles of 3‑weekly pembrolizumab plus ≥9 weeks beyond response, immune‑related adverse events grade ≥ 3, or patient preference. The primary efficacy endpoint is progression‑free survival measured from the start of first‑line treatment to documented disease progression or death. Recruitment is planned from 1 April 2026 to 1 April 2039, with each participant followed for up to 24 months or until progression, death, or withdrawal. Study visits include a screening visit to verify eligibility, a baseline visit coinciding with treatment initiation, regular follow‑up visits aligned with pembrolizumab infusions (approximately every 3 weeks) and additional assessments at defined intervals (e.g., every 12 weeks) to capture efficacy, safety, immune‑related adverse events, and quality‑of‑life data, and a final end‑of‑study visit at 24 months or at the time of discontinuation. Early termination of study participation may occur if the criteria for the discontinuation cohort are met, if severe toxicity necessitates cessation of therapy, or if the participant withdraws consent or is lost to follow‑up.

The investigational product bevacizumab is supplied as a 25 mg/mL concentrate for solution for infusion and is administered intravenously at a dose of 15 mg/kg. The infusion is performed according to the dosing schedule defined in the study protocol, and each administration is recorded in the participant’s infusion log to support compliance monitoring.

The investigational product pembrolizumab is provided as a 25 mg/mL concentrate for solution for infusion and is administered intravenously at a fixed dose of 400 mg. Dosing follows the schedule outlined in the protocol, and infusion records are used to verify adherence to the dosing regimen.

No placebo or additional comparator therapy is specified for this study; all participants receive the experimental agents as described.

Drug administration is conducted in a clinical setting by qualified personnel. Compliance is assessed through documented infusion dates, doses administered, and any missed or delayed visits, with deviations reported to the study monitor.

Efficacy will be evaluated using time‑to‑event and response‑based parameters. The primary endpoint is progression‑free survival, defined as the interval from initiation of first‑line therapy to the first documented disease progression or death from any cause. Secondary efficacy parameters include the proportion of participants free of a PFS event at 12 and 24 months (PFS‑12 and PFS‑24), overall survival, the overall response rate (percentage of patients achieving complete or partial response), the duration of response (time from first documented complete or partial response to progression or death), rates of immune‑related adverse events leading to treatment discontinuation or interruption, incidence of immune‑related endocrinopathies, and changes in quality of life.

Progression and response assessments will be performed at predefined study visits, with disease status documented using standard imaging and clinical criteria. Time‑point analyses for PFS‑12, PFS‑24, overall survival, ORR, and DoR will be conducted using Kaplan‑Meier estimates and proportion calculations for the total cohort and for the observation and discontinuation sub‑cohorts. Quality‑of‑life evaluations will be collected at the scheduled intervals outlined in the protocol and summarized descriptively. All efficacy data will be analyzed according to the intention‑to‑treat population, with subgroup analyses performed for the observation and discontinuation cohorts.