Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

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

Paclitaxel

Carboplatin

Bevacizumab

Albumin-Bound Paclitaxel

Cisplatin

Mitogens

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Participants received bintrafusp alfa until confirmed disease progression, death, unacceptable toxicity and study withdrawal maximum of 2 years (at the discretion of the Investigator).

M7824

Carboplatin was administered intravenously as per standard of care.

Paclitaxel was administered intravenously as per standard of care.

Bevacizumab was administrated as indicated for standard of care.

Cisplatin was administered intravenously as per standard of care.

Participants received radiotherapy as per standard of care.

Radiotherapy

Medical Responsible

This study was to evaluate the safety and tolerability of bintrafusp alfa in combination with other anti-cancer therapies in participants with locally advanced or advanced cervical cancer.

Bintrafusp Alfa Combination Therapy in Participants With Cervical Cancer (INTR@PID 046)

Safety Study of Bintrafusp Alfa in Combination With Other Anti-cancer Therapies in Participants With Locally Advanced or Advanced Cervical Cancer (INTR@PID 046)

Per company policy, following approval of a new product or a new indication for an approved product in both the EU and the US, EMD Serono will share study protocols, anonymized patient level and study level data and redacted clinical study reports from clinical trials in patients with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website https://www.emdgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html

DLT was defined as Adverse Events (AEs) with any of following toxicities: Grade 4 nonhematologic toxicity or hematologic toxicity lasting more than equal to (\>=) 7 days despite medical intervention; Grade 3 nausea, vomiting, and diarrhea lasting \>= 3 days despite supportive care; Any Grade 3 or Grade 4 nonhematologic lab value leading to hospitalization or persisting for \>= 7 days; Grade 3 or Grade 4: grade 3 is defined as absolute neutrophil count (ANC) less than (\<) 1,000/mm3 with a temperature of \> 38.3 degree Celsius (°C); grade 4 is defined as ANC \< 1,000/mm3 with a temperature of \> 38.3°C, with life-threatening consequences; Thrombocytopenia \< 25,000/mm3 associated with bleeding not resulting in hemodynamic instability or a life-threatening bleeding resulting in urgent intervention; Bleeding events \>= Grade 3 occurring within 5 days of bintrafusp alfa treatment; Prolonged delay (\> 3 weeks) in initiating Cycle 2 due to treatment-related toxicity; Grade 5 toxicity.

Adverse Event (AE) was defined any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment. Treatment-Emergent Adverse Events (TEAEs) were defined as events with onset date or worsening during the on-treatment period. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs included serious TEAEs and non-serious TEAEs.

Ceoi was the observed concentration at the end of the infusion period. This was taken directly from the observed Bintrafusp Alfa concentration-time data.

Ctrough was the serum concentration observed immediately before next dosing.

The area under the concentration-time curve (AUC) from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down).

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above the Lower Limit of quantification (LLQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase.

Cmax was obtained directly from the concentration versus time curve.

The time to reach the maximum observed concentration collected during a dosing interval. Tmax was obtained directly from the concentration versus time curve.

Elimination Half Life (T1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. Elimination half-life determined as 0.693/ Lamda z(λz), λz=terminal first order (elimination) rate constant.

A validated method was applied to detect ADAs in the presence of drug in human serum. The ADA titers of positive samples were determined.

Adverse Event (AE) was defined any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment. Treatment-Emergent Adverse Events (TEAEs) were defined as events with onset date or worsening during the on-treatment period. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important.

Merck KGaA, Darmstadt, Germany

EMD Serono Research & Development Institute, Inc.

Participants received 2400 miligrams (mg) Bintrafusp alfa along with 50 milligram per square meter (mg/m\^2) Cisplatin or Carboplatin, Paclitaxel and 15 milligram per kilogram (mg/kg) Bevacizumab every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.

Cohort 1A: Bintrafusp Alfa +Cisplatin/Carboplatin+Paclitaxel+Bevacizumab

Participants received 2400 mg Bintrafusp alfa along with 50 mg/m\^2 Cisplatin or Carboplatin, 175 mg/m\^2 Paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.

Cohort1B: Bintrafusp Alfa +Cisplatin or Carboplatin+Paclitaxel

Participants received 2400 mg Bintrafusp alfa once every 3 weeks along with 40 mg/m\^2 Cisplatin weekly for 5 weeks followed by radiotherapy as per standard care.

Cohort 2: Bintrafusp Alfa + Cisplatin+ Radiotherapy

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Ethnicity

Communication Center

Dose-Limiting Toxicity Analysis (DLT) Set included all participants who completed the DLT period (within 4 weeks after first administration of study intervention) with at least 80 Percent (%) of the planned cumulative dose received during this period for each study intervention and/or who experienced at least one DLT during the DLT period.

Number of Participants With Dose-Limiting Toxicities (DLTs)

Any TEAEs

Any Serious TEAEs

The safety (SAF) analysis set included all participants who were administered any dose of any study intervention.

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

As per changes in planned analysis, the outcome measure related to pharmacokinetics were not assessed.

Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Bintrafusp Alfa

Serum Trough Concentration Levels (Ctrough) of Bintrafusp Alfa

Area Under the Serum Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Bintrafusp Alfa

Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Bintrafusp Alfa

Maximum Observed Serum Concentration (Cmax) of Bintrafusp Alfa

Time to Reach Maximum Serum Concentration (Tmax) of Bintrafusp Alfa

Terminal Elimination Half-Life (T1/2) of Bintrafusp Alfa

As per changes in planned analysis, the outcome measure related to immunogenicity were not assessed.

Number of Participants With Positive Anti-Drug Antibody (ADA) of Bintrafusp Alfa

Dose-Limiting Toxicity Analysis (DLT) Set included all participants who completed the DLT period (within 4 weeks after first administration of study intervention) with at least 80 Percent (%) of the planned cumulative dose received during this period for each study intervention and/or who experienced at least one DLT during the DLT period. Number of Participants Analyzed=participants evaluable for this outcome.

Number of Japanese Participants With Dose-Limiting Toxicities (DLTs)

The safety (SAF) analysis set included all participants who were administered any dose of any study intervention. Number of Participants Analyzed=participants evaluable for this outcome.

Spots Global Cancer Trial Database for Bintrafusp Alfa Combination Therapy in Participants With Cervical Cancer (INTR@PID 046)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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