Biliary Tract Cancer, Cholangiocarcinoma, Gallbladder Cancer
Conditions
Keywords
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
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.
Interventions
DRUGM7824
Participants received an intravenous infusion of 1200 milligrams (mg) M7824 once every 2 weeks until confirmed disease progression, death, unacceptable toxicity or study withdrawal.
Sponsors
Merck KGaA, Darmstadt, Germany
EMD Serono Research & Development Institute, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 was 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 were 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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 data cutoff (assessed up to 736 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. |
| 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 (736 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. |
| 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 data cutoff (assessed up to 736 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. |
| 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 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. |
| 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 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 Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) and assessed by Investigator. |
| 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 (736 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. |
| Overall Survival (OS) | Time from first administration of study drug to data cutoff (assessed up to 736 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. |
| 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 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. |
| 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. |
| Number of Participants With Positive Antidrug Antibodies (ADA) | Time from first treatment to data cutoff (assessed up to 736 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. |
| 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 data cutoff (assessed up to 736 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. |
| 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 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. |
| 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 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. |
| 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 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. |
| 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 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 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. |
| 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 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. |
| Serum Pre-Dose Concentrations (Ctrough) of M7824 | At Day 15, Day 29, Day 43, Day 85, Day 127, Day 169, Day 253, Day 337, Day 421 and Day 505 | Ctrough was defined as the concentration observed immediately before next dosing (corresponding to pre-dose or trough concentration for multiple dosing). |
Countries
China, France, Italy, Japan, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Pre-assignment details
First participant signed informed consent: 26 Mar 2019, Clinical cutoff date: 30 March 2021.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 159 |
| Total | 159 |
Baseline characteristics
| Characteristic | M7824 |
|---|---|
| Age, Continuous | 64 years STANDARD_DEVIATION 8.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 155 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 77 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 18 Participants |
| Race (NIH/OMB) White | 64 Participants |
| Sex: Female, Male Female | 65 Participants |
| Sex: Female, Male Male | 94 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 108 / 159 |
| other Total, other adverse events | 144 / 159 |
| serious Total, serious adverse events | 86 / 159 |
Outcome results
Primary
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)
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 up to 555 days
Population: ITT analysis set included all participants who were administered at least one dose of M7824.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| M7824 | 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 |
Secondary
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)
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 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| M7824 | 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 |
Secondary
Durable Response Rate (DRR) Acoording to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator
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 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| M7824 | 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 |
Secondary
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
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 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| M7824 | 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 |
| M7824 | 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 |
Secondary
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
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 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
Secondary
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)
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 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| M7824 | 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 |
Secondary
Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator
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 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| M7824 | 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 |
Secondary
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
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 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| M7824 | 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 |
| Unknown | 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 | High | — months |
| Unknown | 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 | Unknown (missing) | — months |
Secondary
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
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 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
Secondary
Number of Participants With Positive Antidrug Antibodies (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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| M7824 | Number of Participants With Positive Antidrug Antibodies (ADA) | 45 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs)
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 data cutoff (assessed up to 736 days)
Population: Safety analysis set included all participants who were administered at least one dose of M7824.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| M7824 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs) | TEAEs | 152 Participants |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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
Overall Survival (OS)
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 to data cutoff (assessed up to 736 days)
Population: ITT analysis set included all participants who were administered at least one dose of M7824.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| M7824 | Overall Survival (OS) | 7.6 months |
Secondary
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
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 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
| M7824 | 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 |
Secondary
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
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 data cutoff (assessed up to 736 days)
Population: ITT analysis set included all participants who were administered at least one dose of M7824.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| M7824 | 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 |
Secondary
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
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 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| M7824 | 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 |
| M7824 | 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 |
Secondary
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)
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 (736 days)
Population: ITT analysis set included all participants who were administered at least one dose of M7824.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| M7824 | 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 |
Secondary
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator
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 (736 days)
Population: ITT analysis set included all participants who were administered at least one dose of M7824.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| M7824 | 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 |
Secondary
Serum Concentration at End of Infusion (CEOI) of M7824
Serum Concentration at End of Infusion (CEOI) of M7824 is reported.
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| M7824 | Serum Concentration at End of Infusion (CEOI) of M7824 | Day 1 | 399 mcg/mL | Geometric Coefficient of Variation 31.5 |
| M7824 | Serum Concentration at End of Infusion (CEOI) of M7824 | Day 29 | 434 mcg/mL | Geometric Coefficient of Variation 48.5 |
Secondary
Serum Pre-Dose Concentrations (Ctrough) of M7824
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, 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| M7824 | Serum Pre-Dose Concentrations (Ctrough) of M7824 | Day 15 | 70.7 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 40.7 |
| M7824 | Serum Pre-Dose Concentrations (Ctrough) of M7824 | Day 29 | 84.2 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 58 |
| M7824 | Serum Pre-Dose Concentrations (Ctrough) of M7824 | Day 43 | 93.4 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 52.6 |
| M7824 | Serum Pre-Dose Concentrations (Ctrough) of M7824 | Day 85 | 105 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 42.6 |
| M7824 | Serum Pre-Dose Concentrations (Ctrough) of M7824 | Day 127 | 117 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 41.5 |
| M7824 | Serum Pre-Dose Concentrations (Ctrough) of M7824 | Day 169 | 101 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 55.6 |
| M7824 | Serum Pre-Dose Concentrations (Ctrough) of M7824 | Day 253 | 115 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 46.8 |
| M7824 | Serum Pre-Dose Concentrations (Ctrough) of M7824 | Day 337 | 91.3 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 41.5 |
| M7824 | Serum Pre-Dose Concentrations (Ctrough) of M7824 | Day 421 | 114 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 36.7 |
| M7824 | Serum Pre-Dose Concentrations (Ctrough) of M7824 | Day 505 | NA microgram per milliliter (mcg/mL) | — |