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

• Sponsor: EMD Serono Research & Development Institute, Inc. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03833661
• Collaborator: Merck KGaA, Darmstadt, Germany (Industry)
• Enrollment: 159
• Locations: 33
• Arm: 1
• Anticipated Duration (Months): 42.2
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The study to evaluate M7824 monotherapy in participants with advanced or metastatic biliary tract cancer (BTC) who failed or were intolerant to first-line (1L) chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Biliary Tract Cancer; Cholangiocarcinoma; Gallbladder Cancer	Drug: M7824	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 159 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Multicenter, Open-label Study to Investigate the Clinical Efficacy of M7824 Monotherapy in Participants With Locally Advanced or Metastatic Biliary Tract Cancer Who Fail or Are Intolerant to First-line Platinum-Based Chemotherapy
• Actual Study Start Date: Mar 26, 2019
• Actual Primary Completion Date: Nov 9, 2020
• Anticipated Study Completion Date: Sep 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: M7824	Drug: M7824; Participants received an intravenous infusion of 1200 milligrams (mg) M7824 once every 2 weeks until confirmed disease progression, death, unacceptable toxicity or study withdrawal.; Other Names: Bintrafusp alfa

Outcome Measures

Primary Outcome Measures

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) [Time from first treatment to up to data cutoff (assessed up to 555 days)]

   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.

Secondary Outcome Measures

1. 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) [Time from first documentation of objective response up to data cutoff (assessed up to 555 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.

2. 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) [Time from first treatment to up to data cutoff (assessed up to 555 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.

3. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs) [Time from first treatment to up to data cutoff (assessed up to 555 days)]

   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.

4. Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC) [Time from first administration of study drug until the first documentation of PD or death, assessed up to data-cutoff (555 days)]

   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.

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 the Investigator [Time from first treatment to up to data cutoff (assessed up to 555 days)]

   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 Investigator.

6. Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator [Time from first documentation of objective response up to data cutoff (assessed up to 555 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.

7. Durable Response Rate (DRR) Acoording to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator [Time from first treatment to up to data cutoff (assessed up to 555 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 Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) and assessed by Investigator.

8. Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator [Time from first administration of study drug until the first documentation of PD or death, assessed up to data-cutoff (555 days)]

   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.

9. Overall Survival (OS) [Time from first administration of study drug up to data cutoff (assessed up to 555 days)]

   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.

10. Serum Pre-Dose Concentrations (Ctrough) of M7824 [At Day 15, Day 29, Day 43, Day 85, Day 127, Day 169, Day 253 and Day 337]

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

11. Serum Concentration at End of Infusion (CEOI) of M7824 [At Day 1 and Day 29]

    Serum Concentration at End of Infusion (CEOI) of M7824 is reported.

12. Number of Participants With Positive Antidrug Antibodies (ADA) [Time from first treatment to up to data cutoff (assessed up to 555 days)]

    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.

13. 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 [Time from first treatment to up to data cutoff (assessed up to 555 days)]

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

14. 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 [Time from first treatment to up to data cutoff (assessed up to 555 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.

15. 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 [Time from first documentation of objective response up to data cutoff (assessed up to 555 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.

16. 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 [Time from first documentation of objective response up to data cutoff (assessed up to 555 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.

17. 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 [Time from first treatment to up to data cutoff (assessed up to 555 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 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.

18. 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 [Time from first treatment to up to data cutoff (assessed up to 555 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

• Are participants with histologically or cytologically confirmed locally advanced or metastatic BTC.

• Availability of tumor (primary or metastatic) archival material or fresh biopsies is mandatory

• Participants with BTC must have failed or be intolerant to 1L systemic platinum-based chemotherapy administered for locally advanced or metastatic disease. Only one prior treatment line is allowed

• Disease must be measurable with at least 1 unidimensionally measurable lesion by RECIST 1.1

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 1

• Life expectancy >= 12 weeks as judged by the Investigator

• Adequate hematological function defined by white blood cell (WBC) count >= 3 * 10^9/Litre with absolute neutrophil count (ANC) >= 1.5 * 109/Litre, lymphocyte count

= 0.5 * 10^{9/Litre, platelet count >=75 * 10}9/Litre, and hemoglobin (Hgb) >= 9 grams/decilitre

• Adequate hepatic function defined by a total bilirubin level =< 1.5 * upper limit of normal (ULN), an aspartate aminotransferase (AST) level =< 2.5 * ULN, and an alanine aminotransferase (ALT) level =<2.5 * ULN. For participants with liver involvement in their tumor, AST =< 5.0 * ULN and ALT =< 5.0 * ULN is acceptable

• Adequate coagulation function defined as prothrombin time (PT) or international normalized ratio (INR) =< 1.5 * ULN unless the participant is receiving anticoagulant therapy

• Albumin >= 3.0 grams/decilitre

• Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) positive participants must be treated and on a stable dose of antivirals

• Adequate renal function defined by either creatinine =< 1.5 * ULN or an estimated creatinine clearance (CCr) > 40 milliliter (mL) per minute (min) according to the Cockcroft-Gault formula or by measure of CCr from 24-hour urine collection

• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• Ampullary cancer is excluded

• Significant acute or chronic infections

• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent

• Interstitial lung disease or its history

• Participants who are not eligible for or have not been treated with 1L systemic chemotherapy

• Anticancer treatment within 21 days before the start of study intervention

• Concurrent treatment with nonpermitted drugs

• Prior participation in a M7824 clinical trial

• Prior therapy with other immunotherapy or checkpoint inhibitors, such as anti-PD 1, anti PD L1, anti- cytotoxic T-cell lymphocyte-4 (CTLA-4) antibodies.

• Pregnancy or breast feeding

• Systemic anticancer treatment after failing 1L platinum-based chemotherapy

• Other protocol defined exclusion criteria could apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Arizona	Scottsdale	Arizona	United States	85259
2	UCSF Mount Zion Medical Ctr	San Francisco	California	United States	94158
3	Mayo Clinic in Florida - Department of Neurology	Jacksonville	Florida	United States	32224
4	H. Lee Moffitt Cancer Center and Research Institute, Inc	Tampa	Florida	United States	33612-9497
5	Sidney Kimmel Comprehensive Cancer Center at John Hopkins	Baltimore	Maryland	United States	21231
6	Mayo Clinic - Rochester	Rochester	Minnesota	United States	55905
7	MD Anderson Cancer Center - Unit	Houston	Texas	United States	77030
8	Peking University Cancer Hospital	Beijing		China	100142
9	Affiliated Tumor Hospital of Harbin Medical University	Harbin		China	150081
10	Groupe Hospitalier Sud - Hôpital Haut Lévêque - Service Hepato Gastroentérologie Oncologie Digest	Pessac Cedex		France	33604
11	ICO - Site René Gauducheau	Saint Herblain		France	44805
12	Institut Gustave Roussy	Villejuif cedex		France	94805
13	Istituto Clinico Humanitas	Rozzano	Milano	Italy	20089
14	Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi - Unita' Operativa di Pediatria	Bologna		Italy	40138
15	Fondazione IRCCS Istituto Nazionale dei Tumori Milano	Milano		Italy	20133
16	Policlinico Universitario Agostino Gemelli - UOC Oncologia Medica	Roma		Italy	00168
17	National Cancer Center Hospital - Dept of Hepatobiliary and Pancreatic Oncology	Chuo-ku		Japan	104-0045
18	National Cancer Center Hospital East	Kashiwa-shi		Japan	277-8577
19	Kyorin University Hospital - Dept of Oncology	Mitaka-shi		Japan	181-8611
20	Kindai University Hospital - Dept of Gastroenterology	Osakasayama-shi		Japan	589-8511
21	Kanagawa Cancer Center	Yokohama-shi		Japan	241-8515
22	Seoul National University Bundang Hospital	Seongnam-si		Korea, Republic of	13620
23	Seoul National University Hospital	Seoul		Korea, Republic of	03080
24	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
25	Asan Medical Center	Seoul		Korea, Republic of	05505
26	Samsung Medical Center	Seoul		Korea, Republic of	135-710
27	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain	08027
28	Hospital Universitari Vall d'Hebron - Dept of Oncology	Barcelona		Spain	8035
29	Hospital Universitario HM Madrid Sanchinarro - Servicio de Oncologia	Madrid		Spain	28050
30	Chang Gung Memorial Hospital, Linkou	Linkou		Taiwan	333
31	National Cheng Kung University Hospital	Tainan		Taiwan	704
32	National Taiwan University Hospital	Taipei		Taiwan
33	St James's University Hospital - Dept of Oncology	Leeds		United Kingdom	LS9 7TF

Sponsors and Collaborators

• EMD Serono Research & Development Institute, Inc.
• Merck KGaA, Darmstadt, Germany

Investigators

• Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Study Documents (Full-Text)

• Study Protocol - Jun 22, 2021
• Statistical Analysis Plan - Aug 26, 2020

More Information

Additional Information:

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

Publications

None provided.

• Responsible Party: EMD Serono Research & Development Institute, Inc.
• ClinicalTrials.gov Identifier: NCT03833661
• Other Study ID Numbers: MS200647_0047; 2018-003707-19
• First Posted: Feb 7, 2019
• Last Update Posted: Mar 9, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by EMD Serono Research & Development Institute, Inc.: M7824; Bintrafusp alfa (proposed INN); Transforming growth factor-beta; First-line Platinum-Based Chemotherapy; Programmed death-ligand 1; Metastatic Biliary Tract Cancer; Cholangiocarcinoma; Gallbladder cancer; INTR@PID BTC 047
• Additional relevant MeSH terms: Cholangiocarcinoma; Biliary Tract Neoplasms; Gallbladder Neoplasms

Study Results

Participant Flow

Pre-assignment Detail	First participant signed informed consent: 26 Mar 2019, Primary Analysis cutoff date: 30 September 2020. Primary analysis results are reported. Complete results will be reported within 1 year of study completion date.

Arm/Group Title	M7824
Arm/Group Description	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.
Period Title: Overall Study
STARTED	159
COMPLETED	150
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	M7824
Arm/Group Description	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 Participants	159
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64 (8.9)
Sex: Female, Male (Count of Participants)
Female	65 40.9%
Male	94 59.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 2.5%
Not Hispanic or Latino	155 97.5%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	77 48.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	64 40.3%
More than one race	0 0%
Unknown or Not Reported	18 11.3%

Outcome Measures

1. Primary Outcome

Title	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)
Description	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.
Time Frame	Time from first treatment to up to data cutoff (assessed up to 555 days)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	M7824
Arm/Group Description	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.
Measure Participants	159
Number (95% Confidence Interval) [percentage of participants]	10.1 6.4%

2. Secondary Outcome

Title	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)
Description	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.
Time Frame	Time from first documentation of objective response up to data cutoff (assessed up to 555 days)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	M7824
Arm/Group Description	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.
Measure Participants	16
Median (95% Confidence Interval) [months]	NA

3. Secondary Outcome

Title	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)
Description	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.
Time Frame	Time from first treatment to up to data cutoff (assessed up to 555 days)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	M7824
Arm/Group Description	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.
Measure Participants	159
Number (95% Confidence Interval) [percentage of participants]	4.4 2.8%

4. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs)
Description	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.
Time Frame	Time from first treatment to up to data cutoff (assessed up to 555 days)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	M7824
Arm/Group Description	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.
Measure Participants	159
TEAEs	152 95.6%
Treatment Related TEAEs	99 62.3%
AESI: Infusion-related reaction	10 6.3%
AESI: Immune-related AE	46 28.9%
AESI: TGF-β inhibition mediated skin AE	11 6.9%
AESI: Anemia	43 27%

5. Secondary Outcome

Title	Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)
Description	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.
Time Frame	Time from first administration of study drug until the first documentation of PD or death, assessed up to data-cutoff (555 days)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	M7824
Arm/Group Description	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.
Measure Participants	159
Median (95% Confidence Interval) [months]	1.8

6. Secondary Outcome

Title	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
Description	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 Investigator.
Time Frame	Time from first treatment to up to data cutoff (assessed up to 555 days)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	M7824
Arm/Group Description	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.
Measure Participants	159
Number (95% Confidence Interval) [percentage of participants]	10.7 6.7%

7. Secondary Outcome

Title	Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator
Description	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.
Time Frame	Time from first documentation of objective response up to data cutoff (assessed up to 555 days)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	M7824
Arm/Group Description	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.
Measure Participants	17
Median (95% Confidence Interval) [months]	8.2

8. Secondary Outcome

Title	Durable Response Rate (DRR) Acoording to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator
Description	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 Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) and assessed by Investigator.
Time Frame	Time from first treatment to up to data cutoff (assessed up to 555 days)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	M7824
Arm/Group Description	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.
Measure Participants	159
Number (95% Confidence Interval) [percentage of participants]	5.0 3.1%

9. Secondary Outcome

Title	Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator
Description	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.
Time Frame	Time from first administration of study drug until the first documentation of PD or death, assessed up to data-cutoff (555 days)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	M7824
Arm/Group Description	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.
Measure Participants	159
Median (95% Confidence Interval) [months]	1.8

10. Secondary Outcome

Title	Overall Survival (OS)
Description	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.
Time Frame	Time from first administration of study drug up to data cutoff (assessed up to 555 days)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	M7824
Arm/Group Description	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.
Measure Participants	159
Median (95% Confidence Interval) [months]	7.6

11. Secondary Outcome

Title	Serum Pre-Dose Concentrations (Ctrough) of M7824
Description	Ctrough was defined as the concentration observed immediately before next dosing (corresponding to pre-dose or trough concentration for multiple dosing).
Time Frame	At Day 15, Day 29, Day 43, Day 85, Day 127, Day 169, Day 253 and Day 337

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	M7824
Arm/Group Description	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.
Measure Participants	137
Day 15	70.6 (40.8)
Day 29	84.2 (58.0)
Day 43	93.4 (52.6)
Day 85	105 (42.6)
Day 127	117 (41.5)
Day 169	101 (55.6)
Day 253	115 (46.8)
Day 337	112 (18.4)

12. Secondary Outcome

Title	Serum Concentration at End of Infusion (CEOI) of M7824
Description	Serum Concentration at End of Infusion (CEOI) of M7824 is reported.
Time Frame	At Day 1 and Day 29

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	M7824
Arm/Group Description	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.
Measure Participants	151
Day 1	398 (31.5)
Day 29	434 (48.5)

13. Secondary Outcome

Title	Number of Participants With Positive Antidrug Antibodies (ADA)
Description	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.
Time Frame	Time from first treatment to up to data cutoff (assessed up to 555 days)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	M7824
Arm/Group Description	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.
Measure Participants	157
Count of Participants [Participants]	45 28.3%

14. Secondary Outcome

Title	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
Description	Confirmed objective response was defined as the percentage of participants with a confirmed objective response of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Confirmed CR = at least 2 determinations of CR at least 4 weeks apart and before progression. Confirmed PR = at least 2 determinations of PR at least 4 weeks apart and before progression (and not qualifying for a CR). Confirmed objective response was determined according to RECIST v1.1 and as adjudicated by IRC through PD-L1 Subgroup: 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% were reported.
Time Frame	Time from first treatment to up to data cutoff (assessed up to 555 days)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	M7824
Arm/Group Description	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.
Measure Participants	141
PD-L1 expression on TC: < 1%	10.2 6.4%
PD-L1 expression on TC: >= 1%	7.0 4.4%
PD-L1 expression on TC: < 5%	9.7 6.1%
PD-L1 expression on TC: >= 5%	7.1 4.5%
PD-L1 expression on TC: < 25%	8.7 5.5%
PD-L1 expression on TC: >= 25%	13.3 8.4%
PD-L1 expression on TC: < 50%	9.2 5.8%
PD-L1 expression on TC: >= 50%	9.1 5.7%
PD-L1 expression on IC: < 1%	13.6 8.6%
PD-L1 expression on IC: >= 1%	7.4 4.7%
PD-L1 expression on IC: < 5%	8.7 5.5%
PD-L1 expression on IC: >= 5%	8.3 5.2%
PD-L1 expression on IC: < 25%	7.5 4.7%
PD-L1 expression on IC: >= 25%	20.0 12.6%
PD-L1 expression on IC: < 50%	8.5 5.3%
PD-L1 expression on IC: >= 50%	0.0 0%

15. Secondary Outcome

Title	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
Description	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.
Time Frame	Time from first treatment to up to data cutoff (assessed up to 555 days)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	M7824
Arm/Group Description	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.
Measure Participants	153
High	0.0 0%
Low or Microsatellite stable	10.0 6.3%

16. Secondary Outcome

Title	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
Description	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.
Time Frame	Time from first documentation of objective response up to data cutoff (assessed up to 555 days)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	M7824
Arm/Group Description	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.
Measure Participants	13
PD-L1 expression on TC: < 1%	NA
PD-L1 expression on TC: >= 1%	5.8
PD-L1 expression on TC: < 5%	NA
PD-L1 expression on TC: >= 5%	NA
PD-L1 expression on TC: < 25%	NA
PD-L1 expression on TC: >= 25%	NA
PD-L1 expression on TC: < 50%	NA
PD-L1 expression on TC: >= 50%	NA
PD-L1 expression on IC: < 1%	NA
PD-L1 expression on IC: >= 1%	NA
PD-L1 expression on IC: < 5%	NA
PD-L1 expression on IC: >= 5%	NA
PD-L1 expression on IC: < 25%	NA
PD-L1 expression on IC: >= 25%	NA
PD-L1 expression on IC: < 50%	NA

17. Secondary Outcome

Title	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
Description	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.
Time Frame	Time from first documentation of objective response up to data cutoff (assessed up to 555 days)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	M7824
Arm/Group Description	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.
Measure Participants	15
Low or Microsatellite stable	NA

18. Secondary Outcome

Title	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
Description	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 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.
Time Frame	Time from first treatment to up to data cutoff (assessed up to 555 days)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	M7824
Arm/Group Description	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.
Measure Participants	141
PD-L1 expression on TC: < 1%	6.1 3.8%
PD-L1 expression on TC: >= 1%	2.3 1.4%
PD-L1 expression on TC: < 5%	5.3 3.3%
PD-L1 expression on TC: >= 5%	3.6 2.3%
PD-L1 expression on TC: < 25%	4.8 3%
PD-L1 expression on TC at >= 25%	6.7 4.2%
PD-L1 expression on TC: < 50%	4.6 2.9%
PD-L1 expression on TC: >= 50%	9.1 5.7%
PD-L1 expression on IC: < 1%	9.1 5.7%
PD-L1 expression on IC: >= 1%	3.7 2.3%
PD-L1 expression on IC: < 5%	4.3 2.7%
PD-L1 expression on IC: >= 5%	4.8 3%
PD-L1 expression on IC: < 25%	3.3 2.1%
PD-L1 expression on IC: >= 25%	20.0 12.6%
PD-L1 expression on IC: < 50%	4.7 3%
PD-L1 expression on IC: >= 50%	0.0 0%

19. Secondary Outcome

Title	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
Description	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.
Time Frame	Time from first treatment to up to data cutoff (assessed up to 555 days)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	M7824
Arm/Group Description	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.
Measure Participants	153
High	0.0 0%
Low or Microsatellite stable	4.0 2.5%

Adverse Events

Time Frame	Time from first treatment to up to data cutoff (assessed up to 555 days)
Arm/Group Title	M7824
Arm/Group Description	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.
All Cause Mortality
	M7824
	Affected / at Risk (%)	# Events
Total	93/159 (58.5%)
Serious Adverse Events
	M7824
	Affected / at Risk (%)	# Events
Total	84/159 (52.8%)
Blood and lymphatic system disorders
Anaemia	5/159 (3.1%)
Haemolytic anaemia	1/159 (0.6%)
Cardiac disorders
Myocarditis	1/159 (0.6%)
Ventricular fibrillation	1/159 (0.6%)
Gastrointestinal disorders
Abdominal pain	2/159 (1.3%)
Abdominal pain upper	1/159 (0.6%)
Ascites	2/159 (1.3%)
Colitis	2/159 (1.3%)
Duodenal stenosis	1/159 (0.6%)
Dysphagia	1/159 (0.6%)
Gastric stenosis	1/159 (0.6%)
Gastritis erosive	1/159 (0.6%)
Gastrointestinal haemorrhage	1/159 (0.6%)
Gastrointestinal vascular malformation haemorrhagic	1/159 (0.6%)
Haemorrhoidal haemorrhage	1/159 (0.6%)
Ileus	1/159 (0.6%)
Mechanical ileus	1/159 (0.6%)
Nausea	1/159 (0.6%)
Small intestinal obstruction	1/159 (0.6%)
Upper gastrointestinal haemorrhage	1/159 (0.6%)
Vomiting	2/159 (1.3%)
General disorders
Asthenia	1/159 (0.6%)
Disease progression	15/159 (9.4%)
Fatigue	1/159 (0.6%)
General physical health deterioration	2/159 (1.3%)
Multiple organ dysfunction syndrome	1/159 (0.6%)
Pyrexia	2/159 (1.3%)
Hepatobiliary disorders
Bile duct obstruction	3/159 (1.9%)
Bile duct stenosis	3/159 (1.9%)
Cholangitis	8/159 (5%)
Cholangitis acute	2/159 (1.3%)
Cholestasis	1/159 (0.6%)
Hepatic failure	4/159 (2.5%)
Hepatitis	1/159 (0.6%)
Hepatocellular injury	1/159 (0.6%)
Jaundice	1/159 (0.6%)
Jaundice cholestatic	3/159 (1.9%)
Liver injury	2/159 (1.3%)
Infections and infestations
Abdominal infection	1/159 (0.6%)
Bacterial sepsis	1/159 (0.6%)
Biliary tract infection	6/159 (3.8%)
Bursitis infective	1/159 (0.6%)
COVID-19	1/159 (0.6%)
Infective spondylitis	1/159 (0.6%)
Osteomyelitis	1/159 (0.6%)
Pneumonia	2/159 (1.3%)
Pyelonephritis acute	1/159 (0.6%)
Sepsis	3/159 (1.9%)
Staphylococcal infection	1/159 (0.6%)
Subcutaneous abscess	1/159 (0.6%)
Urosepsis	1/159 (0.6%)
Varicella zoster pneumonia	1/159 (0.6%)
Varicella zoster virus infection	1/159 (0.6%)
Vascular device infection	1/159 (0.6%)
Metabolism and nutrition disorders
Decreased appetite	3/159 (1.9%)
Hyponatraemia	2/159 (1.3%)
Latent autoimmune diabetes in adults	1/159 (0.6%)
Musculoskeletal and connective tissue disorders
Back pain	1/159 (0.6%)
Myositis	1/159 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma	1/159 (0.6%)
Keratoacanthoma	1/159 (0.6%)
Malignant ascites	1/159 (0.6%)
Tumour hyperprogression	1/159 (0.6%)
Tumour necrosis	1/159 (0.6%)
Tumour pain	1/159 (0.6%)
Nervous system disorders
Immune-mediated encephalitis	1/159 (0.6%)
Psychiatric disorders
Delirium	1/159 (0.6%)
Renal and urinary disorders
Acute kidney injury	3/159 (1.9%)
Nephritis	1/159 (0.6%)
Reproductive system and breast disorders
Prostatitis	1/159 (0.6%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis	1/159 (0.6%)
Interstitial lung disease	1/159 (0.6%)
Pleural effusion	1/159 (0.6%)
Pulmonary embolism	1/159 (0.6%)
Skin and subcutaneous tissue disorders
Lichenoid keratosis	1/159 (0.6%)
Pemphigoid	1/159 (0.6%)
Rash	1/159 (0.6%)
Rash maculo-papular	2/159 (1.3%)
Toxic skin eruption	1/159 (0.6%)
Surgical and medical procedures
Biliary stent placement	1/159 (0.6%)
Vascular disorders
Hypertension	1/159 (0.6%)
Other (Not Including Serious) Adverse Events
	M7824
	Affected / at Risk (%)	# Events
Total	130/159 (81.8%)
Blood and lymphatic system disorders
Anaemia	41/159 (25.8%)
Endocrine disorders
Hypothyroidism	9/159 (5.7%)
Gastrointestinal disorders
Abdominal pain	19/159 (11.9%)
Ascites	8/159 (5%)
Constipation	22/159 (13.8%)
Diarrhoea	12/159 (7.5%)
Nausea	21/159 (13.2%)
Vomiting	11/159 (6.9%)
General disorders
Asthenia	22/159 (13.8%)
Fatigue	22/159 (13.8%)
Oedema peripheral	10/159 (6.3%)
Pyrexia	24/159 (15.1%)
Injury, poisoning and procedural complications
Infusion related reaction	8/159 (5%)
Investigations
Alanine aminotransferase increased	22/159 (13.8%)
Aspartate aminotransferase increased	25/159 (15.7%)
Blood alkaline phosphatase increased	16/159 (10.1%)
Blood bilirubin increased	13/159 (8.2%)
Metabolism and nutrition disorders
Decreased appetite	34/159 (21.4%)
Hypoalbuminaemia	15/159 (9.4%)
Hyponatraemia	10/159 (6.3%)
Musculoskeletal and connective tissue disorders
Back pain	9/159 (5.7%)
Nervous system disorders
Headache	10/159 (6.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	9/159 (5.7%)
Epistaxis	8/159 (5%)
Skin and subcutaneous tissue disorders
Pruritus	29/159 (18.2%)
Rash	19/159 (11.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.