The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) plus one of four platinum-based chemotherapy regimens compared to the efficacy and safety of placebo plus one of four platinum-based chemotherapy regimens in the treatment of adult women with persistent, recurrent, or metastatic cervical cancer. Possible chemotherapy regimens include: paclitaxel plus cisplatin with or without bevacizumab and paclitaxel plus carboplatin with or without bevacizumab. The primary study hypotheses are that the combination of pembrolizumab plus chemotherapy is superior to placebo plus chemotherapy with respect to: 1) Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by the Investigator, or, 2) Overall Survival (OS).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
617
IV infusion
IV infusion
IV infusion
IV infusion
IV infusion
IV infusion
Alaska Women's Cancer Care ( Site 1770)
Anchorage, Alaska, United States
Arizona Oncology Associates, PC- HAL ( Site 8005)
Phoenix, Arizona, United States
UC Irvine Health ( Site 1796)
Orange, California, United States
Smilow Cancer Hospital at Yale New Haven ( Site 1809)
New Haven, Connecticut, United States
H. Lee Moffitt Cancer Center and Research Institute ( Site 1754)
Tampa, Florida, United States
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator in Participants With Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1
PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 as assessed by Investigator for all randomized participants with PD-L1 CPS ≥1 is presented.
Time frame: Up to approximately 46 months
PFS Per RECIST 1.1 as Assessed by Investigator in All Participants
PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 as assessed by Investigator for all randomized participants is presented.
Time frame: Up to approximately 46 months
PFS Per RECIST 1.1 as Assessed by Investigator in Participants With PD-L1 CPS ≥10
PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 as assessed by Investigator for all randomized participants with PD-L1 CPS ≥10 is presented.
Time frame: Up to approximately 46 months
Overall Survival (OS) in Participants With PD-L1 CPS ≥1
OS was defined as the time from randomization to death due to any cause. The OS for all randomized participants with PD-L1 CPS ≥1 is presented.
Time frame: Up to approximately 46 months
OS in All Participants
OS was defined as the time from randomization to death due to any cause. The OS for all randomized participants is presented.
Time frame: Up to approximately 46 months
OS in Participants With PD-L1 CPS ≥10
OS was defined as the time from randomization to death due to any cause. The OS for all randomized participants with PD-L1 CPS ≥10 is presented.
Time frame: Up to approximately 46 months
Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator
ORR was defined as the percentage of the participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters). The ORR per RECIST 1.1 as assessed by Investigator is presented.
Time frame: Up to approximately 46 months
Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator
For participants who demonstrate CR or PR, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. The DOR per RECIST 1.1 as assessed by Investigator is presented.
Time frame: Up to approximately 46 months
Percentage of Participants That Were PFS Event-Free (PFS Rate) at Month 12 Per RECIST 1.1 as Assessed by Investigator
PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS Rate was defined as the percentage of participants that were PFS event-free at Month 12. The PFS Rate per RECIST 1.1 as assessed by Investigator at Month 12 is presented.
Time frame: 12 months
PFS Per RECIST 1.1 as Assessed by Blinded Independent Central Review (BICR)
PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 as assessed by BICR is presented.
Time frame: Up to approximately 46 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Georgia Cancer Center at Augusta University ( Site 1767)
Augusta, Georgia, United States
Barbara Ann Karmanos Cancer Institute ( Site 1785)
Detroit, Michigan, United States
Henry Ford Health System ( Site 1810)
Detroit, Michigan, United States
Washington University School of Medicine ( Site 1779)
St Louis, Missouri, United States
Cancer Institute of New Jersey at University Hospital ( Site 1762)
Newark, New Jersey, United States
...and 139 more locations
Number of Participants Who Experienced an Adverse Event (AE)
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experienced an AE is presented.
Time frame: Up to approximately 66 months
Number of Participants Who Experienced a Serious AE (SAE)
An SAE was defined as any untoward medical occurrence that, at any dose: a.) Resulted in death; b.) Was life-threatening; c.) Required inpatient hospitalization or prolongation of existing hospitalization; d.) Resulted in persistent or significant disability/incapacity; e.) Was a congenital anomaly/birth defect; f.) Other important medical events; h.) Was a new cancer (that is not a condition of the study) or i.) Was associated with an overdose. The number of participants who experienced an SAE is presented.
Time frame: Up to approximately 66 months
Number of Participants Who Experienced an Immune-related AE (irAE)
AEs associated with pembrolizumab exposure may be a result of an immune response. These irAEs may occur shortly after the first dose or several months after the last dose of pembrolizumab treatment and may affect more than one body system simultaneously. For this study irAEs included, but were not limited to: -Pneumonitis; * Diarrhea/Colitis; * Aspartate transaminase (AST)/Alanine transaminase (ALT) elevation or Increased bilirubin; * Type 1 diabetes mellitus or Hyperglycemia; * Hypophysitis; * Hyperthyroidism; * Hypothyroidism; * Nephritis and Renal dysfunction; and * Myocarditis. The number of participants who experienced an irAE is presented.
Time frame: Up to approximately 66 months
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued study treatment due to an AE is presented.
Time frame: Up to approximately 63 months
Number of Participants With a 10-point Change From Baseline in Quality of Life (QoL) Based on the European Organisation for the Research & Treatment of Cancer (EORTC) QoL Questionnaire-30 (QLQ-C30) Combined Global Score
The EORTC QLQ-C30 is a questionnaire to assess the quality of life of cancer patients. Participant responses to "How would you rate your overall health during the past week?" (Item 29) and "How would you rate your overall quality of life during the past week?" (Item 30) are scored on a 7-point scale (1= Very poor to 7=Excellent). Raw scores are standardized with linear transformation so that scores range from 0-100. A higher combined score indicates a better overall health status. Participant post-baseline scores were classified based on change from baseline, "Improved": a ≥10-point improvement in score and confirmed by the next visit; "Stable": a ≥10-point increase or \<10-point change in score OR a \<10-point change in score and a ≥10-point increase in score at the next visit; or "Deteriorated": a ≥10-point deterioration in score when the criteria for improvement/stability weren't met. Participants who didn't meet "Improved", "Stable", or "Deteriorated" criteria reported as "Other".
Time frame: Baseline (Cycle 1 Day 1: Predose) and up to approximately 46 months