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

Phase 2

Completed

Conditions: Cholangiocarcinoma
Gallbladder Cancer
Biliary Tract Cancer

Interventions: Drug: M7824

Registration Number: NCT03833661

Lead Sponsor: EMD Serono Research & Development Institute, Inc.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 159

Inclusion Criteria

Not provided

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 exclusion criteria could apply

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
M7824	M7824	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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 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 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).
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.
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.
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.
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.
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) 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.
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) 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 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.
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.
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.

Trial Locations

Locations (33): MD Anderson Cancer Center - Unit
🇺🇸
Houston, Texas, United States
Kindai University Hospital - Dept of Gastroenterology
🇯🇵
Osakasayama-shi, Japan
Hospital de la Santa Creu i Sant Pau
🇪🇸
Barcelona, Spain
Chang Gung Memorial Hospital, Linkou
🇨🇳
Linkou, Taiwan
National Taiwan University Hospital
🇨🇳
Taipei, Taiwan
Mayo Clinic Arizona
🇺🇸
Scottsdale, Arizona, United States
Mayo Clinic in Florida - Department of Neurology
🇺🇸
Jacksonville, Florida, United States
UCSF Mount Zion Medical Ctr
🇺🇸
San Francisco, California, United States
H. Lee Moffitt Cancer Center and Research Institute, Inc
🇺🇸
Tampa, Florida, United States
Sidney Kimmel Comprehensive Cancer Center at John Hopkins
🇺🇸
Baltimore, Maryland, United States
Mayo Clinic - Rochester
🇺🇸
Rochester, Minnesota, United States
Peking University Cancer Hospital
🇨🇳
Beijing, China
Affiliated Tumor Hospital of Harbin Medical University
🇨🇳
Harbin, China
Istituto Clinico Humanitas
🇮🇹
Rozzano, Milano, Italy
Institut Gustave Roussy
🇫🇷
Villejuif cedex, France
Groupe Hospitalier Sud - Hôpital Haut Lévêque - Service Hepato Gastroentérologie Oncologie Digest
🇫🇷
Pessac Cedex, France
ICO - Site René Gauducheau
🇫🇷
Saint Herblain, France
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi - Unita' Operativa di Pediatria
🇮🇹
Bologna, Italy
National Cancer Center Hospital - Dept of Hepatobiliary and Pancreatic Oncology
🇯🇵
Chuo-ku, Japan
Kyorin University Hospital - Dept of Oncology
🇯🇵
Mitaka-shi, Japan
Policlinico Universitario Agostino Gemelli - UOC Oncologia Medica
🇮🇹
Roma, Italy
National Cancer Center Hospital East
🇯🇵
Kashiwa-shi, Japan
Fondazione IRCCS Istituto Nazionale dei Tumori Milano
🇮🇹
Milano, Italy
Kanagawa Cancer Center
🇯🇵
Yokohama-shi, Japan
Seoul National University Bundang Hospital
🇰🇷
Seongnam-si, Korea, Republic of
Seoul National University Hospital
🇰🇷
Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷
Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷
Seoul, Korea, Republic of
Hospital Universitari Vall d'Hebron - Dept of Oncology
🇪🇸
Barcelona, Spain
Hospital Universitario HM Madrid Sanchinarro - Servicio de Oncologia
🇪🇸
Madrid, Spain
National Cheng Kung University Hospital
🇨🇳
Tainan, Taiwan
St James's University Hospital - Dept of Oncology
🇬🇧
Leeds, United Kingdom
Asan Medical Center
🇰🇷
Seoul, Korea, Republic of