Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Uterine Cervical Neoplasms

Death

Disease Progression

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

Camurati-Engelmann Disease

All Drugs and Chemicals

Mitogens

Participants received an intravenous infusion of 1200 milligrams (mg) bintrafusp alfa once every 2 weeks until confirmed disease progression, death, unacceptable toxicity and study withdrawal.

Bintrafusp alfa

Medical Responsible

The main purpose of this study was to evaluate clinical efficacy and safety of bintrafusp alfa in participants with advanced, unresectable cervical cancer with disease progression during or after platinum-containing chemotherapy.

Bintrafusp Alfa Monotherapy in Platinum-Experienced Cervical Cancer

A Phase II, Multicenter, Open Label Study of Bintrafusp Alfa (M7824) Monotherapy in Participants With Advanced, Unresectable Cervical Cancer With Disease Progression During or After Platinum-Containing Chemotherapy

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

Confirmed objective response was defined as the number of participants with a confirmed objective response of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Confirmed CR = at least 2 determinations of CR at least 4 weeks apart and before progression. Confirmed PR = at least 2 determinations of PR at least 4 weeks apart and before progression (and not qualifying for a CR). Confirmed objective response was determined according to RECIST v1.1 and as adjudicated by IRC.

DOR was defined for participants with confirmed response, as the time from first documentation of confirmed objective response (Complete Response \[CR\] or Partial Response \[PR\]) according to RECIST 1.1 to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. DOR was determined according to RECIST v1.1 and assessed by IRC. Results were calculated based on Kaplan-Meier estimates.

Durable Response was defined as the number of participants with confirmed objective response (CR or PR) according to RECIST 1.1, determined by IRC with duration of at least 6 months. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

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. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs: TEAEs was defined as events with onset date or worsening during the on-treatment period. TEAEs included serious AEs and non-serious AEs. Treatment-related TEAEs: reasonably related to the study intervention. AESIs included Infusion-related reactions, Immune-related AEs, Transforming growth factor- beta (TGF-ß) inhibition mediated skin AE, bleeding and anemia.

PFS was defined as the time from first administration of study intervention until date of the first documentation of disease progression (PD) or death due to any cause, whichever occurred first. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Kaplan-Meier estimates was used to calculate PFS.

Confirmed objective response was defined as the number of participants with a confirmed objective response of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Confirmed CR = at least 2 determinations of CR at least 4 weeks apart and before progression. Confirmed PR = at least 2 determinations of PR at least 4 weeks apart and before progression (and not qualifying for a CR). Confirmed objective response was determined according to RECIST v1.1 and as adjudicated by Investigator.

OS was defined as the time from first administration of study intervention to the date of death due to any cause. The OS was analyzed by using the Kaplan-Meier method.

Ctrough was defined as the concentration observed immediately before next dosing (corresponding to pre-dose or trough concentration for multiple dosing).

Serum Concentration at End of Infusion (CEOI) of bintrafusp alfa is reported.

Serum samples were analyzed by a validated assay method to detect the presence of antidrug antibodies (ADA). Number of participants with positive ADA were reported.

Confirmed objective response was defined as the percentage of participants with a confirmed objective response of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Confirmed CR = at least 2 determinations of CR at least 4 weeks apart and before progression. Confirmed PR = at least 2 determinations of PR at least 4 weeks apart and before progression (and not qualifying for a CR). Confirmed objective response was determined according to RECIST v1.1 and as adjudicated by IRC through PD-L1 Subgroup. Participants with PD-L1 positive tumors (Combined positive score (CPS) \>=1) and PD-L1 negative tumors (CPS\<1).

PFS was defined as the time from first administration of study intervention until the first documentation of disease progression (PD) or death due to any cause, whichever occurred first. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was determined according to RECIST v1.1 and as adjudicated by IRC through PD-L1 Subgroup. Participants with PD-L1 positive tumors (Combined positive score (CPS) \>=1) and PD-L1 negative tumors (CPS\<1).

OS was defined as the time from first administration of study intervention to the date of death due to any cause. The OS was analyzed by using the Kaplan-Meier method. Participants with PD-L1 positive tumors (Combined positive score (CPS) \>=1) and PD-L1 negative tumors (CPS\<1).

Merck KGaA, Darmstadt, Germany

EMD Serono Research & Development Institute, Inc.

Participants received an intravenous infusion of 1200 milligrams (mg) bintrafusp alfa once every 2 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.

Bintrafusp Alfa

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

The Full analysis set (FAS) included all participants, who were administered at least one dose of bintrafusp alfa.

Communication Center

FAS included all participants who were administered at least one dose of bintrafusp alfa.

Number of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)

Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)

Durable Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)

TEAE's

Treatment Related TEAEs

AESI: Infusion-related reaction

AESI: Immune-related AE

AESI: TGF-beta inhibition mediated skin AE

AESI: Anemia

AESI: Bleeding events

Safety analysis set included all participants who were administered at least one dose of bintrafusp alfa

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs)

Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)

Number of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator

Overall Survival (OS)

Day 15

Day 29

Day 43

Day 85

Day 127

Day 169

Day 253

Day 337

Day 421

Day 505

Day 589

Pharmacokinetic (PK) analysis set included all participants who completed at least one dose of bintrafusp alfa and who provided at least one sample with a measurable concentration of bintrafusp alfa. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "number analyzed" signifies those participants who were evaluable at specified time points for this outcome measure.

Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa

Day 1

PK analysis set included all participants who completed at least one dose of Bintrafusp Alfa and who provided at least one sample with a measurable concentration of Bintrafusp Alfa. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "number analyzed" signifies those participants who were evaluable at specified time points for this outcome measure.

Serum Concentration at End of Infusion (CEOI) of Bintrafusp Alfa

Immunogenicity analysis set included all participants who received at least one dose of bintrafusp alfa and who had at least one valid result of ADA.

Number of Participants With Positive Antidrug Antibodies (ADA)

PD-L1 positive tumors (CPS>=1)

PD-L1 negative tumors (CPS <1)

FAS included all participants who were administered at least one dose of bintrafusp alfa. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "number analyzed" signifies those participants who were evaluable at specified categories for this outcome measure.

Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression

PD-L1 negative tumors (CPS<1)

PFS According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression

Overall Survival (OS) as Assessed According to Programmed Death Ligand 1 (PD-L1) Expression

Overall Study

Antineoplastic Agents

Paclitaxel

Carboplatin

Bevacizumab

Albumin-Bound Paclitaxel

Cisplatin

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

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)

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.

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

Ethnicity

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Bintrafusp Alfa Monotherapy in Platinum-Experienced Cervical Cancer	NCT04246489	Uterine Cervica...	Bintrafusp alfa	18 Years -	EMD Serono
Bintrafusp Alfa Combination Therapy in Participants With Cervical Cancer (INTR@PID 046)	NCT04551950	Cervical Cancer	M7824 Carboplatin Paclitaxel Bevacizumab Cisplatin Radiotherapy	18 Years -	EMD Serono
Bintrafusp Alfa Monotherapy in Platinum-Experienced Cervical Cancer	NCT04246489	Uterine Cervica...	Bintrafusp alfa	18 Years -	EMD Serono

Spots Global Cancer Trial Database for intr@pid

Every month we try and update this database with for intr@pid cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for intr@pid

Every month we try and update this database with for intr@pid cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for intr@pid cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.