Trial Outcomes & Findings for M7824 Monotherapy in Locally Advanced or Metastatic Second Line (2L) Biliary Tract Cancer (Cholangiocarcinoma and Gallbladder Cancer) (NCT NCT03833661)

Last Updated: 2023-10-25

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

159 participants

Primary outcome timeframe

Time from first treatment up to 555 days

Results posted on

2023-10-25

Participant Flow

First participant signed informed consent: 26 Mar 2019, Clinical cutoff date: 30 March 2021.

Participant milestones

Participant milestones
Measure	M7824 Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
Overall Study STARTED	159
Overall Study COMPLETED	159
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

M7824 Monotherapy in Locally Advanced or Metastatic Second Line (2L) Biliary Tract Cancer (Cholangiocarcinoma and Gallbladder Cancer)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	M7824 n=159 Participants Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
Age, Continuous	64 years STANDARD_DEVIATION 8.9 • n=5 Participants
Sex: Female, Male Female	65 Participants n=5 Participants
Sex: Female, Male Male	94 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	155 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	77 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	64 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	18 Participants n=5 Participants

PRIMARY outcome

Timeframe: Time from first treatment up to 555 days

Population: ITT analysis set included all participants who were administered at least one dose of M7824.

Outcome measures

Outcome measures
Measure	M7824 n=159 Participants Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
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)	10.7 percentage of participants Interval 6.4 to 16.6

SECONDARY outcome

Timeframe: Time from first documentation of objective response to data cutoff (assessed up to 736 days)

DOR was defined for participants with confirmed response, as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) 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.

Outcome measures

Outcome measures
Measure	M7824 n=17 Participants Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
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)	10.0 months Interval 3.9 to The upper limit could not be estimated due to insufficient number of events by the date of data cutoff.

SECONDARY outcome

Timeframe: Time from first treatment to data cutoff (assessed up to 736 days)

DRR was defined as the percentage of participants with confirmed objective response (CR or PR) 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. DRR was determined according to RECIST v1.1 and assessed by IRC.

Outcome measures

Outcome measures
Measure	M7824 n=17 Participants Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
Durable Response Rate (DRR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)	6.3 percentage of participants Interval 3.1 to 11.3

SECONDARY outcome

Timeframe: Time from first treatment to data cutoff (assessed up to 736 days)

Population: Safety analysis set included all participants who were administered at least one dose of M7824.

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-β) inhibition mediated skin AE and anemia.

Outcome measures

Outcome measures
Measure	M7824 n=159 Participants Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs) TEAEs	152 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs) Treatment Related TEAEs	99 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs) AESI: Infusion-related reaction	10 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs) AESI: Immune-related AE	46 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs) AESI: TGF-β inhibition mediated skin AE	13 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs) AESI: Anemia	44 Participants

SECONDARY outcome

Timeframe: Time from first administration of study drug until the first documentation of PD or death, assessed up to data-cutoff (736 days)

Population: ITT analysis set included all participants who were administered at least one dose of M7824.

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.

Outcome measures

Outcome measures
Measure	M7824 n=159 Participants Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)	1.8 months Interval 1.7 to 1.8

SECONDARY outcome

Timeframe: Time from first treatment to data cutoff (assessed up to 736 days)

Population: ITT analysis set included all participants who were administered at least one dose of M7824.

Outcome measures

Outcome measures
Measure	M7824 n=159 Participants Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
Percentage 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	10.7 percentage of participants Interval 6.4 to 16.6

SECONDARY outcome

Timeframe: Time from first documentation of objective response to data cutoff (assessed up to 736 days)

DOR was defined for participants with confirmed response, as the time from first documentation of objective response (Complete Response \[CR\] or Partial Rresponse \[PR\]) 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 Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) and assessed by Investigator. Results were calculated based on Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	M7824 n=17 Participants Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator	8.2 months Interval 3.9 to 12.0

SECONDARY outcome

Timeframe: Time from first treatment to data cutoff (assessed up to 736 days)

Outcome measures

Outcome measures
Measure	M7824 n=17 Participants Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
Durable Response Rate (DRR) Acoording to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator	5.7 percentage of participants Interval 2.6 to 10.5

SECONDARY outcome

Timeframe: Time from first administration of study drug until the first documentation of PD or death, assessed up to data-cutoff (736 days)

Population: ITT analysis set included all participants who were administered at least one dose of M7824.

Outcome measures

Outcome measures
Measure	M7824 n=159 Participants Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator	1.8 months Interval 1.7 to 1.8

SECONDARY outcome

Timeframe: Time from first administration of study drug to data cutoff (assessed up to 736 days)

Population: ITT analysis set included all participants who were administered at least one dose of M7824.

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.

Outcome measures

Outcome measures
Measure	M7824 n=159 Participants Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
Overall Survival (OS)	7.6 months Interval 5.8 to 9.5

SECONDARY outcome

Timeframe: At Day 15, Day 29, Day 43, Day 85, Day 127, Day 169, Day 253, Day 337, Day 421 and Day 505

Population: Pharmacokinetic (PK) analysis set included all participants who completed at least one dose of M7824 and who provided at least one sample with a measurable concentration of M7824. 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.

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

Outcome measures

Outcome measures
Measure	M7824 n=138 Participants Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
Serum Pre-Dose Concentrations (Ctrough) of M7824 Day 29	84.2 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 58.0
Serum Pre-Dose Concentrations (Ctrough) of M7824 Day 43	93.4 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 52.6
Serum Pre-Dose Concentrations (Ctrough) of M7824 Day 85	105 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 42.6
Serum Pre-Dose Concentrations (Ctrough) of M7824 Day 15	70.7 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 40.7
Serum Pre-Dose Concentrations (Ctrough) of M7824 Day 127	117 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 41.5
Serum Pre-Dose Concentrations (Ctrough) of M7824 Day 169	101 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 55.6
Serum Pre-Dose Concentrations (Ctrough) of M7824 Day 253	115 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 46.8
Serum Pre-Dose Concentrations (Ctrough) of M7824 Day 337	91.3 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 41.5
Serum Pre-Dose Concentrations (Ctrough) of M7824 Day 421	114 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 36.7
Serum Pre-Dose Concentrations (Ctrough) of M7824 Day 505	NA microgram per milliliter (mcg/mL) Geometric Coefficient of Variation NA Geometric Mean and Geometric Coefficient of Variation were not calculated if fewer than 3 participants have reportable parameter values.

SECONDARY outcome

Timeframe: At Day 1 and Day 29

Population: PK analysis set included all participants who completed at least one dose of M7824 and who provided at least one sample with a measurable concentration of M7824. 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 M7824 is reported.

Outcome measures

Outcome measures
Measure	M7824 n=152 Participants Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
Serum Concentration at End of Infusion (CEOI) of M7824 Day 1	399 mcg/mL Geometric Coefficient of Variation 31.5
Serum Concentration at End of Infusion (CEOI) of M7824 Day 29	434 mcg/mL Geometric Coefficient of Variation 48.5

SECONDARY outcome

Timeframe: Time from first treatment to data cutoff (assessed up to 736 days)

Population: Immunogenicity analysis set included all participants who received at least one dose of M7824 and who had at least one valid result of ADA.

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.

Outcome measures

Outcome measures
Measure	M7824 n=157 Participants Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
Number of Participants With Positive Antidrug Antibodies (ADA)	45 Participants

SECONDARY outcome

Timeframe: Time from first treatment to data cutoff (assessed up to 736 days)

Population: ITT analysis set included all participants who were administered at least one dose of M7824. 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 for the specified categories for this outcome measure.

Outcome measures

Outcome measures
Measure	M7824 n=141 Participants Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
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 expression on TC: < 1%	10.2 percentage of participants Interval 5.0 to 18.0
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 expression on TC: >= 1%	7.0 percentage of participants Interval 1.5 to 19.1
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 expression on TC: < 5%	9.7 percentage of participants Interval 5.0 to 16.8
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 expression on TC: >= 5%	7.1 percentage of participants Interval 0.9 to 23.5
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 expression on TC: < 25%	8.7 percentage of participants Interval 4.4 to 15.1
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 expression on TC: >= 25%	13.3 percentage of participants Interval 1.7 to 40.5
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 expression on TC: < 50%	9.2 percentage of participants Interval 4.9 to 15.6
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 expression on TC: >= 50%	9.1 percentage of participants Interval 0.2 to 41.3
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 expression on IC: < 1%	13.6 percentage of participants Interval 2.9 to 34.9
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 expression on IC: >= 1%	7.4 percentage of participants Interval 3.3 to 14.1
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 expression on IC: < 5%	8.7 percentage of participants Interval 2.4 to 20.8
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 expression on IC: >= 5%	8.3 percentage of participants Interval 3.4 to 16.4
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 expression on IC: < 25%	7.5 percentage of participants Interval 3.5 to 13.8
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 expression on IC: >= 25%	20.0 percentage of participants Interval 2.5 to 55.6
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 expression on IC: < 50%	8.5 percentage of participants Interval 4.3 to 14.7
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 expression on IC: >= 50%	0.0 percentage of participants Interval 0.0 to 97.5

SECONDARY outcome

Timeframe: Time from first treatment to data cutoff (assessed up to 736 days)

Confirmed OR was defined as the percentage of participants with a confirmed OR of CR or 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 OR was determined according to RECIST v1.1 and as adjudicated by IRC through MSI Status subgroups as:- MSI High = if participant is MSI High for any (at least one) test;- Microsatellite stable (MSS) or MSI Low = if participant is not MSI High for any test;- Unknown (missing) = no MSI tests available at baseline was reported. MSI high: if 2 or more unstable markers were detected in sample; MSI low: if 1 marker was unstable and remaining markers were stable and MSS if all markers were stable.

Outcome measures

Outcome measures
Measure	M7824 n=153 Participants Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
Percentage of Participants With Confirmed Objective Response as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Independent Review Committee (IRC) According to Microsatellite Instability (MSI) Status High	0.0 percentage of participants Interval 0.0 to 70.8
Percentage of Participants With Confirmed Objective Response as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Independent Review Committee (IRC) According to Microsatellite Instability (MSI) Status Low or Microsatellite stable	10.0 percentage of participants Interval 5.7 to 16.0

SECONDARY outcome

Timeframe: Time from first documentation of objective response to data cutoff (assessed up to 736 days)

DOR was defined for participants with confirmed response, as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) 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 as adjudicated by IRC through PD-L1 Subgroup: PD-L1 expression on tumor cells (TC) and on immune cells (IC) at baseline and in the following categories: \<1%, \>=1%, \<5%, \>=5%, \<25%, \>=25%, \<50%, \>=50% was reported.

Outcome measures

Outcome measures
Measure	M7824 n=13 Participants Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on TC: < 1%	NA months Interval 3.4 to Due to small number of events, Median and Upper limit of 95% Confidence Interval from Kaplan-Meier survival curves could not derive.
Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on TC: >= 1%	5.8 months Interval 3.9 to Due to small number of events, Median and Upper limit of 95% Confidence Interval from Kaplan-Meier survival curves could not derive.
Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on TC: < 5%	NA months Interval 3.4 to Due to small number of events, Median and Upper limit of 95% Confidence Interval from Kaplan-Meier survival curves could not derive.
Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on TC: >= 5%	NA months Interval 3.9 to Due to small number of events, Median and Upper limit of 95% Confidence Interval from Kaplan-Meier survival curves could not derive.
Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on TC: < 25%	NA months Interval 3.4 to Due to small number of events, Median and Upper limit of 95% Confidence Interval from Kaplan-Meier survival curves could not derive.
Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on TC: >= 25%	NA months Interval 3.9 to Due to small number of events, Median and Upper limit of 95% Confidence Interval from Kaplan-Meier survival curves could not derive.
Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on TC: < 50%	NA months Interval 3.7 to Due to small number of events, Median and Upper limit of 95% Confidence Interval from Kaplan-Meier survival curves could not derive.
Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on TC: >= 50%	NA months Due to small number of events, Median and Upper limit of 95% Confidence Interval from Kaplan-Meier survival curves could not derive.
Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on IC: < 1%	NA months Interval 3.4 to Due to small number of events, Median and Upper limit of 95% Confidence Interval from Kaplan-Meier survival curves could not derive.
Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on IC: >= 1%	NA months Interval 3.7 to Due to small number of events, Median and Upper limit of 95% Confidence Interval from Kaplan-Meier survival curves could not derive.
Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on IC: < 5%	NA months Interval 3.4 to Due to small number of events, Median and Upper limit of 95% Confidence Interval from Kaplan-Meier survival curves could not derive.
Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on IC: >= 5%	NA months Interval 3.9 to Due to small number of events, Median and Upper limit of 95% Confidence Interval from Kaplan-Meier survival curves could not derive.
Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on IC: < 25%	NA months Interval 3.4 to Due to small number of events, Median and Upper limit of 95% Confidence Interval from Kaplan-Meier survival curves could not derive.
Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on IC: >= 25%	NA months Due to small number of events, Median and Upper limit of 95% Confidence Interval from Kaplan-Meier survival curves could not derive.
Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on IC: < 50%	NA months Interval 3.4 to Due to small number of events, Median and Upper limit of 95% Confidence Interval from Kaplan-Meier survival curves could not derive.

SECONDARY outcome

Timeframe: Time from first documentation of objective response to data cutoff (assessed up to 736 days)

DOR was defined for participants with confirmed response, as the time from first documentation of objective response (CR) or (PR) to the date of first documentation of 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 % 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 as adjudicated by IRC through MSI Status subgroups as:- MSI High = if participant is MSI High for any (at least one) test;- MSS or MSI Low = if participant is not MSI High for any test;- Unknown (missing) = no MSI tests available at baseline was reported. MSI high: if 2 or more unstable markers were detected in sample; MSI low: if 1 marker was unstable and remaining markers were stable and MSS if all markers were stable.

Outcome measures

Outcome measures
Measure	M7824 n=15 Participants Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to According to Microsatellite Instability (MSI) Status Low or Microsatellite stable	NA months Interval 3.7 to Due to small number of events, Median and Upper limit of 95% Confidence Interval from Kaplan-Meier survival curves could not derive.

SECONDARY outcome

Timeframe: Time from first treatment to data cutoff (assessed up to 736 days)

Outcome measures

Outcome measures
Measure	M7824 n=141 Participants Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
Durable Response Rate (DRR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on TC: < 1%	6.1 percentage of participants Interval 2.3 to 12.9
Durable Response Rate (DRR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on TC: >= 1%	2.3 percentage of participants Interval 0.1 to 12.3
Durable Response Rate (DRR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on TC: < 5%	5.3 percentage of participants Interval 2.0 to 11.2
Durable Response Rate (DRR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on TC: >= 5%	3.6 percentage of participants Interval 0.1 to 18.3
Durable Response Rate (DRR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on TC: < 25%	4.8 percentage of participants Interval 1.8 to 10.1
Durable Response Rate (DRR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on TC at >= 25%	6.7 percentage of participants Interval 0.2 to 31.9
Durable Response Rate (DRR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on TC: < 50%	4.6 percentage of participants Interval 1.7 to 9.8
Durable Response Rate (DRR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on TC: >= 50%	9.1 percentage of participants Interval 0.2 to 41.3
Durable Response Rate (DRR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on IC: < 1%	9.1 percentage of participants Interval 1.1 to 29.2
Durable Response Rate (DRR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on IC: >= 1%	3.7 percentage of participants Interval 1.0 to 9.2
Durable Response Rate (DRR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on IC: < 5%	4.3 percentage of participants Interval 0.5 to 14.8
Durable Response Rate (DRR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on IC: >= 5%	4.8 percentage of participants Interval 1.3 to 11.7
Durable Response Rate (DRR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on IC: < 25%	3.3 percentage of participants Interval 0.9 to 8.3
Durable Response Rate (DRR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on IC: >= 25%	20.0 percentage of participants Interval 2.5 to 55.6
Durable Response Rate (DRR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on IC: < 50%	4.7 percentage of participants Interval 1.7 to 9.8
Durable Response Rate (DRR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression PD-L1 expression on IC: >= 50%	0.0 percentage of participants Interval 0.0 to 97.5

SECONDARY outcome

Timeframe: Time from first treatment to data cutoff (assessed up to 736 days)

DRR was defined as the percentage of participants with confirmed OR (CR or PR) 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 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. DRR was determined according to RECIST v1.1 and adjudicated by IRC through MSI Status subgroups as:- MSI High = if participant is MSI High for any (at least one) test;- MSS or MSI Low = if participant is not MSI High for any test;- Unknown (missing) = no MSI tests available at baseline was reported. MSI high: if 2 or more unstable markers were detected in sample; MSI low: if 1 marker was unstable and remaining markers were stable and MSS if all markers were stable.

Outcome measures

Outcome measures
Measure	M7824 n=153 Participants Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
Durable Response Rate (DRR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to According to Microsatellite Instability (MSI) Status High	0.0 percentage of participants Interval 0.0 to 70.8
Durable Response Rate (DRR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to According to Microsatellite Instability (MSI) Status Low or Microsatellite stable	4.0 percentage of participants Interval 1.5 to 8.5

Adverse Events

M7824

Serious events: 86 serious events

Other events: 144 other events

Deaths: 108 deaths

Serious adverse events

Serious adverse events
Measure	M7824 n=159 participants at risk Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
Blood and lymphatic system disorders Anaemia	3.1% 5/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Blood and lymphatic system disorders Haemolytic anaemia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Cardiac disorders Myocarditis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Cardiac disorders Ventricular fibrillation	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Abdominal pain	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Abdominal pain upper	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Ascites	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Colitis	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Duodenal stenosis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Dysphagia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Gastric stenosis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Gastritis erosive	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Gastrointestinal haemorrhage	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Gastrointestinal vascular malformation haemorrhagic	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Ileus	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Mechanical ileus	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Nausea	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Small intestinal obstruction	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Vomiting	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
General disorders Asthenia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
General disorders Disease progression	10.1% 16/159 • Time from first treatment to data cutoff (assessed up to 736 days)
General disorders Fatigue	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
General disorders General physical health deterioration	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
General disorders Multiple organ dysfunction syndrome	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
General disorders Pyrexia	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Hepatobiliary disorders Bile duct obstruction	1.9% 3/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Hepatobiliary disorders Bile duct stenosis	1.9% 3/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Hepatobiliary disorders Cholangitis	5.0% 8/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Hepatobiliary disorders Cholangitis acute	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Hepatobiliary disorders Cholestasis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Hepatobiliary disorders Hepatic failure	2.5% 4/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Hepatobiliary disorders Hepatitis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Hepatobiliary disorders Hepatocellular injury	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Hepatobiliary disorders Jaundice	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Hepatobiliary disorders Jaundice cholestatic	1.9% 3/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Hepatobiliary disorders Liver injury	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Abdominal infection	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Bacterial sepsis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Biliary tract infection	3.8% 6/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Bursitis infective	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations COVID-19	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Infective spondylitis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Osteomyelitis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Pneumonia	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Pyelonephritis acute	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Sepsis	1.9% 3/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Staphylococcal infection	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Subcutaneous abscess	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Urosepsis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Varicella zoster pneumonia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Varicella zoster virus infection	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Vascular device infection	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Metabolism and nutrition disorders Decreased appetite	1.9% 3/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Metabolism and nutrition disorders Hyponatraemia	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Metabolism and nutrition disorders Latent autoimmune diabetes in adults	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Musculoskeletal and connective tissue disorders Back pain	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Musculoskeletal and connective tissue disorders Myositis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Keratoacanthoma	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant ascites	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour hyperprogression	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour necrosis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Nervous system disorders Immune-mediated encephalitis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Psychiatric disorders Delirium	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Renal and urinary disorders Acute kidney injury	1.9% 3/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Renal and urinary disorders Nephritis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Reproductive system and breast disorders Prostatitis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Lichenoid keratosis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Pemphigoid	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Rash	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Rash maculo-papular	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Toxic skin eruption	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Surgical and medical procedures Biliary stent placement	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Vascular disorders Hypertension	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Musculoskeletal and connective tissue disorders Pain in extremity	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)

Other adverse events

Other adverse events
Measure	M7824 n=159 participants at risk Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
Investigations Blood albumin decreased	2.5% 4/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations Blood albumin increased	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations Bilirubin conjugated increased	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations Blood cholesterol increased	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations Blood creatinine increased	4.4% 7/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations Cell marker increased	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations C-reactive protein increased	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations Gamma-glutamyltransferase increased	3.1% 5/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations Blood glucose increased	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations Heart rate increased	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations Blood lactate dehydrogenase increased	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations Blood potassium decreased	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations Blood sodium decreased	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations Blood thyroid stimulating hormone increased	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations International normalised ratio increased	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations Lipase increased	3.8% 6/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations Blood urea increased	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations Liver function test increased	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations Lymphocyte count decreased	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations Platelet count decreased	3.8% 6/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations Weight decreased	4.4% 7/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Metabolism and nutrition disorders Electrolyte imbalance	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Metabolism and nutrition disorders Hyperammonaemia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Metabolism and nutrition disorders Hypercalcaemia	3.1% 5/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Metabolism and nutrition disorders Hyperglycaemia	3.1% 5/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Metabolism and nutrition disorders Hyperkalaemia	2.5% 4/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Metabolism and nutrition disorders Hypernatraemia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Metabolism and nutrition disorders Hypokalaemia	3.1% 5/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Metabolism and nutrition disorders Hypomagnesaemia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Metabolism and nutrition disorders Hypophosphataemia	1.9% 3/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Metabolism and nutrition disorders Hypocalcaemia	1.9% 3/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Metabolism and nutrition disorders Type 1 diabetes mellitus	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Musculoskeletal and connective tissue disorders Arthralgia	6.3% 10/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Metabolism and nutrition disorders Hypoproteinaemia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Metabolism and nutrition disorders Steroid diabetes	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Musculoskeletal and connective tissue disorders Myalgia	1.9% 3/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Musculoskeletal and connective tissue disorders Myositis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Musculoskeletal and connective tissue disorders Bone pain	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Musculoskeletal and connective tissue disorders Muscle discomfort	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Musculoskeletal and connective tissue disorders Muscle spasms	1.9% 3/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Injury, poisoning and procedural complications Toxicity to various agents	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Injury, poisoning and procedural complications Upper limb fracture	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations Activated partial thromboplastin time prolonged	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations Amylase increased	3.1% 5/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Blood and lymphatic system disorders Anaemia	25.8% 41/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Endocrine disorders Hypothyroidism	5.7% 9/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Abdominal pain	13.2% 21/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Ascites	5.0% 8/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Constipation	15.1% 24/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Diarrhoea	8.2% 13/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Nausea	14.5% 23/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Vomiting	7.5% 12/159 • Time from first treatment to data cutoff (assessed up to 736 days)
General disorders Asthenia	14.5% 23/159 • Time from first treatment to data cutoff (assessed up to 736 days)
General disorders Fatigue	14.5% 23/159 • Time from first treatment to data cutoff (assessed up to 736 days)
General disorders Oedema peripheral	6.9% 11/159 • Time from first treatment to data cutoff (assessed up to 736 days)
General disorders Pyrexia	15.7% 25/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Injury, poisoning and procedural complications Infusion related reaction	5.0% 8/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations Alanine aminotransferase increased	15.1% 24/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations Aspartate aminotransferase increased	16.4% 26/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations Blood alkaline phosphatase increased	10.7% 17/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Investigations Blood bilirubin increased	10.1% 16/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Metabolism and nutrition disorders Decreased appetite	21.4% 34/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Metabolism and nutrition disorders Hypoalbuminaemia	10.1% 16/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Metabolism and nutrition disorders Hyponatraemia	6.9% 11/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Musculoskeletal and connective tissue disorders Back pain	6.9% 11/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Nervous system disorders Headache	6.9% 11/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.0% 8/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Respiratory, thoracic and mediastinal disorders Epistaxis	5.0% 8/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Pruritus	18.2% 29/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Rash	12.6% 20/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Blood and lymphatic system disorders Anaemia of malignant disease	26.4% 42/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Blood and lymphatic system disorders Increased tendency to bruise	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Blood and lymphatic system disorders Leukocytosis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Blood and lymphatic system disorders Myelosuppression	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Blood and lymphatic system disorders Neutropenia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Blood and lymphatic system disorders Thrombocytopenia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Cardiac disorders Atrial fibrillation	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Cardiac disorders Pericardial effusion	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Ear and labyrinth disorders Vertigo	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Endocrine disorders Adrenal insufficiency	2.5% 4/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Endocrine disorders Hypercalcaemia of malignancy	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Endocrine disorders Hyperthyroidism	4.4% 7/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Endocrine disorders Hypophysitis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Endocrine disorders Hypopituitarism	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Eye disorders Diplopia	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Eye disorders Dry eye	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Eye disorders Lacrimation increased	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Eye disorders Uveitis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Eye disorders Vision blurred	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Abdominal discomfort	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Abdominal distension	3.8% 6/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Abdominal pain upper	2.5% 4/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Anal haemorrhage	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Angular cheilitis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Colitis	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Dry mouth	1.9% 3/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Duodenal ulcer	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Duodenitis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Dyspepsia	4.4% 7/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Enterocolitis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Eructation	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Flatulence	1.9% 3/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Gastritis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Gastrointestinal haemorrhage	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Gastrooesophageal reflux disease	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Gingival bleeding	4.4% 7/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Haematochezia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Haemorrhoidal haemorrhage	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Haemorrhoids	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Hiatus hernia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Large intestine polyp	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Melaena	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Mouth haemorrhage	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Portal hypertensive gastropathy	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Proctalgia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Stomatitis	1.9% 3/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Toothache	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Gastrointestinal disorders Upper gastrointestinal haemorrhage	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
General disorders Chest discomfort	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
General disorders Chest pain	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
General disorders Chills	2.5% 4/159 • Time from first treatment to data cutoff (assessed up to 736 days)
General disorders Disease progression	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
General disorders Generalised oedema	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
General disorders Influenza like illness	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
General disorders Malaise	3.1% 5/159 • Time from first treatment to data cutoff (assessed up to 736 days)
General disorders Mucosal haemorrhage	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
General disorders Mucosal inflammation	2.5% 4/159 • Time from first treatment to data cutoff (assessed up to 736 days)
General disorders Non-cardiac chest pain	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
General disorders Oedema	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
General disorders Pain	2.5% 4/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Hepatobiliary disorders Biliary obstruction	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Hepatobiliary disorders Cholangitis	1.9% 3/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Hepatobiliary disorders Cholelithiasis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Hepatobiliary disorders Hepatitis	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Hepatobiliary disorders Hyperbilirubinaemia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Hepatobiliary disorders Jaundice	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Hepatobiliary disorders Jaundice cholestatic	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Hepatobiliary disorders Liver disorder	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Hepatobiliary disorders Liver injury	1.9% 3/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Immune system disorders Contrast media allergy	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Immune system disorders Hypersensitivity	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Immune system disorders Infusion related hypersensitivity reaction	1.9% 3/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Bacteraemia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Bacterial vaginosis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Bronchitis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Candida infections	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Biliary tract infection	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Conjunctivitis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Device related infection	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Gingivitis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Herpes oesophagitis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Herpes zoster	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Infection	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Nasopharyngitis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Osteomyelitis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Periodontitis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Pneumonia	3.1% 5/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Pyuria	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Rhinitis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Skin infection	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Staphylococcal skin infection	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Upper respiratory tract infection	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Urinary tract infection	2.5% 4/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Infections and infestations Vulvovaginal candidiasis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Injury, poisoning and procedural complications Contusion	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Injury, poisoning and procedural complications Fall	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Injury, poisoning and procedural complications Limb traumatic amputation	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Injury, poisoning and procedural complications Rib fracture	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Musculoskeletal and connective tissue disorders Neck pain	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Musculoskeletal and connective tissue disorders Pain in extremity	3.1% 5/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Musculoskeletal and connective tissue disorders Sarcopenia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Musculoskeletal and connective tissue disorders Spinal pain	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Anogenital warts	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Infected neoplasm	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Keratoacanthoma	5.0% 8/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lip squamous cell carcinoma	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanocytic naevus	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Seborrhoeic keratosis	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	1.9% 3/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Nervous system disorders Amnesia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Nervous system disorders Dizziness	3.1% 5/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Nervous system disorders Hypoaesthesia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Nervous system disorders Neuropathy peripheral	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Nervous system disorders Peripheral sensory neuropathy	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Nervous system disorders Seizure	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Nervous system disorders Syncope	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Nervous system disorders Visual field defect	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Psychiatric disorders Anxiety	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Psychiatric disorders Delirium	1.9% 3/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Psychiatric disorders Depression	2.5% 4/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Psychiatric disorders Insomnia	5.0% 8/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Renal and urinary disorders Acute kidney injury	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Renal and urinary disorders Azotaemia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Renal and urinary disorders Chromaturia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Renal and urinary disorders Haematuria	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Renal and urinary disorders Nephritis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Renal and urinary disorders Nocturia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Renal and urinary disorders Renal failure	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Renal and urinary disorders Renal injury	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Renal and urinary disorders Tubulointerstitial nephritis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Renal and urinary disorders Urinary incontinence	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Renal and urinary disorders Urinary retention	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Reproductive system and breast disorders Benign prostatic hyperplasia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Reproductive system and breast disorders Nipple pain	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Reproductive system and breast disorders Prostatitis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Reproductive system and breast disorders Pruritus genital	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Reproductive system and breast disorders Scrotal oedema	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Respiratory, thoracic and mediastinal disorders Cough	4.4% 7/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Respiratory, thoracic and mediastinal disorders Dysphonia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Respiratory, thoracic and mediastinal disorders Hypoxia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.9% 3/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Respiratory, thoracic and mediastinal disorders Productive cough	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Respiratory, thoracic and mediastinal disorders Pulmonary artery thrombosis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Respiratory, thoracic and mediastinal disorders Sputum increased	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Acanthosis nigricans	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Actinic keratosis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Decubitus ulcer	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Dermatitis	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Dermatitis acneiform	3.1% 5/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Dermatitis allergic	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Dermatitis bullous	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Dry skin	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Eczema	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Eczema asteatotic	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Erythema	2.5% 4/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Erythema nodosum	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Hyperhidrosis	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Hyperkeratosis	1.9% 3/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Intertrigo	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Keratosis pilaris	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Lichenoid keratosis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Milia	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Night sweats	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Pigmentation disorder	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Psoriasis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Rash macular	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Rash maculo-papular	3.1% 5/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Rash pruritic	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Scab	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Seborrhoeic dermatitis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Skin exfoliation	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Skin mass	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Skin ulcer	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Toxic skin eruption	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Skin and subcutaneous tissue disorders Urticaria	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Vascular disorders Embolism	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Vascular disorders Flushing	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Vascular disorders Haematoma	1.3% 2/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Vascular disorders Hot flush	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Vascular disorders Hypertension	5.0% 8/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Vascular disorders Hypotension	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Vascular disorders Orthostatic hypotension	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)
Vascular disorders Phlebitis	0.63% 1/159 • Time from first treatment to data cutoff (assessed up to 736 days)

Additional Information

Communication Center

Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place