Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Recurrence

Uterine Cervical Neoplasms

Death

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Paclitaxel

Carboplatin

Bevacizumab

Pembrolizumab

Albumin-Bound Paclitaxel

Cisplatin

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Immune Checkpoint Inhibitors

On Day 1 of each 21-day cycle, participants receive an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m\^2 PLUS cisplatin 50 mg/m\^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m\^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments are administered until disease progression or toxicity.

On Day 1 of each 21-day cycle, participants receive an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m\^2 PLUS cisplatin 50 mg/m\^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m\^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments are administered until disease progression or toxicity.

Placebo to pembrolizumab

Medical Director

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).

Efficacy and Safety Study of First-line Treatment With Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Women With Persistent, Recurrent, or Metastatic Cervical Cancer (MK-3475-826/KEYNOTE-826)

A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Chemotherapy Plus Placebo for the First-Line Treatment of Persistent, Recurrent, or Metastatic Cervical Cancer (KEYNOTE-826)

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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.

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.

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.

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.

OS was defined as the time from randomization to death due to any cause. The OS for all randomized participants is presented.

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.

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.

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.

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.

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.

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.

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.

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.

The number of participants who discontinued study treatment due to an AE is presented.

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".

Merck Sharp & Dohme LLC

Serious and Other adverse events (AEs) included all participants who received ≥1 dose of study drug. All-Cause Mortality included all randomized participants. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study treatment. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" \& "Disease progression" not related to study treatment are excluded as AEs. Data are reported by treatment received.

On Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m\^2 PLUS cisplatin 50 mg/m\^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m\^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.

Pembrolizumab+Chemotherapy

On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m\^2 PLUS cisplatin 50 mg/m\^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m\^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.

Placebo+Chemotherapy

Eligible participants received up to 17 additional administrations (up to approximately 1 year) of pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.

Pembrolizumab (Second Course)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

PD-L1 CPS<1

1≤ PD-L1 CPS<10

PD-L1 CPS≥10

Participants were assessed for their PD-L1 tumor expression level by immunohistochemistry assay using tumor tissue. Randomization of participants in the study were stratified by their PD-L1 CPS at baseline (PD-L1 CPS\<1, 1≤ PD-L1 CPS\<10, or PD-L1 CPS≥10).

Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) Status

Randomization of participants was stratified by whether they were metastatic at initial diagnosis (Yes or No). Metastatic was defined as Stage IV based on the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) (2009).

Metastatic at Initial Diagnosis

Randomization of participants was stratified by the Investigator's choice for the participant to receive bevacizumab (Yes or No).

Investigator Choice to Use Bevacizumab

Senior Vice President, Global Clinical Development

Treatment comparison (hazard ratio \[HR\]) was based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by metastatic at initial diagnosis (FIGO \[2009\] stage IVB) (yes or no), bevacizumab use (yes or no), and PD-L1 status (CPS\<1, CPS 1 to \<10, or CPS ≥10).

All randomized participants with PD-L1 CPS ≥1 based on the treatment group to which they were randomized.

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

Treatment comparison (HR) was based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by metastatic at initial diagnosis (FIGO \[2009\] stage IVB) (yes or no), bevacizumab use (yes or no), and PD-L1 status (CPS\<1, CPS 1 to \<10, or CPS ≥10).

All randomized participants based on the treatment group to which they were randomized.

PFS Per RECIST 1.1 as Assessed by Investigator in All Participants

All randomized participants with PD-L1 CPS ≥10 based on the treatment group to which they were randomized.

PFS Per RECIST 1.1 as Assessed by Investigator in Participants With PD-L1 CPS ≥10

Overall Survival (OS) in Participants With PD-L1 CPS ≥1

OS in All Participants

OS in Participants With PD-L1 CPS ≥10

Treatment comparison was based on Miettinen \& Nurminen method stratified by metastatic at initial diagnosis (FIGO \[2009\] stage IVB) (yes or no), bevacizumab use (yes or no), and PD-L1 status (CPS\<1, CPS 1 to \<10, or CPS ≥10).

Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator

All randomized participants based on the treatment group to which they were randomized who demonstrated CR or PR.

Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator

Percentage of Participants That Were PFS Event-Free (PFS Rate) at Month 12 Per RECIST 1.1 as Assessed by Investigator

PFS Per RECIST 1.1 as Assessed by Blinded Independent Central Review (BICR)

All randomized participants who received at least one dose of study treatment.

Number of Participants Who Experienced an Adverse Event (AE)

Number of Participants Who Experienced a Serious AE (SAE)

Number of Participants Who Experienced an Immune-related AE (irAE)

Number of Participants Who Discontinued Study Treatment Due to an AE

Improved

Stable

Deteriorated

Other

Per protocol, all randomized participants who received at least one dose of study treatment and completed at least one EORTC QLQ-C30 assessment were analyzed. Participants with no EORTC QLQ-C30 assessment were not included in the analysis.

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

Overall Study

Urinary Bladder Neoplasms

Urologic Neoplasms

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Anti-Infective Agents

Gemcitabine

Fluorouracil

Mitomycins

Mitomycin

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Alkylating Agents

Enzyme Inhibitors

Participants receive pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.

Participants receive placebo to pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.

400 mg of IV (intravenous) pembrolizumab once every 6 weeks.

64 Gy of radiation administered to participant's bladder only. Thirty-two fractions will be administered over 6.5 weeks.

Conventional Radiotherapy (Bladder only)

64 Gy of radiation administered to participant's bladder and pelvic nodes. Thirty-two fractions will be administered over 6.5 weeks.

Conventional Radiotherapy (Bladder and pelvic nodes)

55 Gy of radiation administered to participant's bladder only. Twenty fractions will be administered over 4 weeks.

Hypofractionated Radiotherapy (Bladder only)

35 mg of cisplatin per cubic meter of body volume, administered once weekly via IV infusion.

5-FU administered via IV infusion at a dose of 500 mg per cubic meter of body volume on Days 1-5 and 22-26.

Fluorouracil (5-FU)

MMC administered via IV infusion at a dose of 12 mg per cubic meter of body volume on Day 1.

Mitomycin C (MMC)

Gemcitabine administered via IV infusion at a dose of 27 mg per cubic meter of body volume twice weekly.

Placebo to intravenous (IV) pembrolizumab administered once every 6 weeks.

Placebo to Pembrolizumab

Toll Free Number

Study Coordinator

This study is designed to assess the antitumor efficacy and safety of pembrolizumab in combination with chemoradiotherapy (CRT) versus CRT alone in participants with muscle-invasive bladder cancer (MIBC). The primary hypothesis is that pembrolizumab + chemoradiotherapy is superior to placebo + chemoradiotherapy with respect to bladder intact event-free survival.

All Sponsor personnel will be blinded to treatment assignments, with the exception of designated unblinded team members. Chemoradiotherapy will be administered to all participants and will be open-label.

Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Chemoradiotherapy (CRT) Versus CRT Alone in Muscle-invasive Bladder Cancer (MIBC) (MK-3475-992/KEYNOTE-992)

A Phase 3, Randomized, Double-blind, Placebo-controlled Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Chemoradiotherapy (CRT) Versus CRT Alone in Participants With Muscle-invasive Bladder Cancer (MIBC) (KEYNOTE-992)

BI-EFS is defined as the time from randomization to any of the following events: residual/recurrent MIBC post-chemoradiotherapy (CRT), nodal or distant metastases as assessed by computerized tomography (CT) and CT urography (CTU) or magnetic resonance urography (MRU) per blinded independent central review (BICR) and/or biopsy results assessed by central pathology review, radical cystectomy, or death due to any cause. If biopsy is not feasible due to participant safety, the imaging alone will be sufficient. The BI-EFS for all participants will be presented.

Time from randomization to death due to any cause.

MFS is defined as the time from randomization to the first documented occurrence of nodal or distant metastases as assessed by CT and CTU or MRU per BICR and/or biopsy results assessed by central pathology review If biopsy is not feasible due to participant safety, the imaging alone will be sufficient.

Time to occurrence of low-grade disease, defined as the time from randomization until the development of NMIBC, will be presented.

An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be presented.

An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be presented.

The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1=Very Poor to 7=Excellent). A higher score indicates a better overall outcome. The change from baseline in Global Health Status/Quality of Life (EORTC QLQ-C30 Items 29 and 30) combined score will be presented.

EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a better quality of life. The change from baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) combined score will be presented.

The BCI is a validated, condition-specific health questionnaire assessing quality of life among participants with bladder cancer. The BCI contains 36 items which assess 3 domains (urinary, bowel, and sexual) with function and bother subdomains. Scores range from 0 to 100 with higher scores corresponding to better functioning and health-related quality of life. The change from baseline in the combined scores of the urinary, bowel, and sexual domains of the BCI will be presented.

The EQ-5D-5L VAS records the respondent's self-rated health on a 10 cm vertical, visual analogue scale. It is rated by the respondent on a scale 0 to 100, with 0 being "the worst health you can imagine" and 100 being "the best health you can imagine". The change from baseline in EQ-5D-5L VAS will be presented.

The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1=Very Poor to 7=Excellent). A higher score indicates a better overall outcome. TTD in Global Health Status/Quality of Life is defined as the time from baseline to the first onset of a 10 point or greater decrease from baseline in the Global Health Status/Quality of Life (EORTC QLQ-C30 Items 29 and 30) combined score, with or without subsequent confirmation.

EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a better quality of life. TTD in Physical Functioning (EORTC QLQ-C30 Items 1-5) combined score is defined as the time from baseline (at randomization) to the first onset of a ≥10-point decrease with confirmation by the subsequent visit of a ≥10-point decrease in physical functioning Items 1 to 5 scale scores.

The BCI is a validated, condition-specific health questionnaire assessing quality of life among participants with bladder cancer. The BCI contains 36 items which assess 3 domains (urinary, bowel, and sexual) with function and bother subdomains. Scores range from 0 to 100 with higher scores corresponding to better functioning and health-related quality of life. TTD in BCI is defined as a 6, 7, and 7 points or greater worsening from baseline for urinary, bowel, and sexual domains, respectively, with or without subsequent confirmation, under a right-censoring rule.

The EQ-5D-5L VAS records the respondent's self-rated health on a 10 cm vertical, visual analogue scale. It is rated by the respondent on a scale 0 to 100, with 0 being "the worst health you can imagine" and 100 being "the best health you can imagine". TTD in EQ-5D-5L VAS is defined as the time from baseline to the first onset of a 7 point or greater decrease from baseline in EQ-5D-5L VAS, with or without subsequent confirmation, under a right-censoring rule.

Time to cystectomy is defined as time from a participant's randomization to date of cystectomy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy and Safety Study of First-line Treatment With Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Women With Persistent, Recurrent, or Metastatic Cervical Cancer (MK-3475-826/KEYNOTE-826)	NCT03635567	Cervical Cancer	Pembrolizumab Paclitaxel Cisplatin Carboplatin Bevacizumab Placebo to pemb...	18 Years -	Merck Sharp & Dohme LLC
Efficacy and Safety Study of First-line Treatment With Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Women With Persistent, Recurrent, or Metastatic Cervical Cancer (MK-3475-826/KEYNOTE-826)	NCT03635567	Cervical Cancer	Pembrolizumab Paclitaxel Cisplatin Carboplatin Bevacizumab Placebo to pemb...	18 Years -	Merck Sharp & Dohme LLC
Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Chemoradiotherapy (CRT) Versus CRT Alone in Muscle-invasive Bladder Cancer (MIBC) (MK-3475-992/KEYNOTE-992)	NCT04241185	Urinary Bladder...	Pembrolizumab Conventional Ra... Conventional Ra... Hypofractionate... Cisplatin Fluorouracil (5... Mitomycin C (MM... Gemcitabine Placebo to Pemb...	18 Years -	Merck Sharp & Dohme LLC
Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Chemoradiotherapy (CRT) Versus CRT Alone in Muscle-invasive Bladder Cancer (MIBC) (MK-3475-992/KEYNOTE-992)	NCT04241185	Urinary Bladder...	Pembrolizumab Conventional Ra... Conventional Ra... Hypofractionate... Cisplatin Fluorouracil (5... Mitomycin C (MM... Gemcitabine Placebo to Pemb...	18 Years -	Merck Sharp & Dohme LLC

Spots Global Cancer Trial Database for placebo to pembrolizumab