MSB0011359C

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.

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.

A DLT was defined as any grade greater than or equal to (\>=) 3 adverse event suspected to be related to investigational medicinal product (IMP) by the Investigator and / or Sponsor occurring in the DLT evaluation period confirmed by the Safety Monitoring Committee (SMC) to be relevant for the IMP treatment.

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Serious AE: 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. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs.

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Serious AE: 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. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs: reasonably related to the study intervention. Number of participants with TEAEs and treatment related TEAEs were reported.

Adverse event (AE): any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Serious AE: 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. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs.

Treatment-related TEAEs are any untoward medical occurrence in a participant who received study drug with causal relationship with the investigational product as assessed by the investigator. Related TEAEs were events with relationship missing, unknown or yes. Number of participants With treatment-related TEAEs, treatment-related serious TEAEs and treatment-related TEAE leading to death were reported.

AEs were graded according to severity using NCI-CTCAE Version 4.03. Severity of TEAEs were graded as Grade 1: mild (not causing any significant problem, dose adjustment not required), Grade 2: moderate (caused problem that does not interfere significantly with usual activities or the clinical status, dose adjustment needed due to adverse event), Grade 3: Severe (caused problem that interferes significantly with usual activities or the clinical status, study drug stopped due to adverse event), Grade 4: Life-threatening, Grade 5: Death. Number of Participants with TEAEs and Related TEAEs Based on Severity having Grade greater than or equal to (\>=) 3 and Grade \>=4 were reported.

A DLT was defined as any grade \>= 3 Adverse Event (AE) suspected to be related to IMP by the Investigator and / or Sponsor occurring in the DLT evaluation period confirmed by the Safety Monitoring Committee (SMC) to be relevant for the IMP treatment. According to the NCI-CTCAE, v4.03, occurring in the DLT evaluation period and assessed to be related to study treatment by the Investigator and / or Sponsor confirmed by the safety monitoring committee to be relevant for the study treatment.

BOR according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and as adjudicated by the Independent Endpoint Review Committee (IRC). BOR is defined as sum of complete response and partial response (CR+PR). For target lesions (TLs), CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the sum of largest diameter (SLD) of the TLs, taking as a reference the baseline SLD.

DCR is defined as the percentage of participants with a confirmed CR+PR+SD+ Non-CR/non-PD at any time as per RANO criteria. A responder is a participant with a Complete Response (CR) or Partial Response (PR), and a non-responder is a participant with Stable Disease (SD) or Progressive Disease (PD) assessed by the RANO criteria. CR is no T1 gadolinium enhancing disease, no new lesions, or corticosteroids, and stable or decreasing T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR). PR is ≥50% decrease in T1 gadolinium enhancing disease, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increasing clinical status. SD is \<50% decrease in T1 gadolinium enhancing disease but \< 25% increase, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increase in clinical status. PD is ≥25% increase in T1 gadolinium enhancing disease.