Clinical Trials List
Protocol NumberMS200647_0047
NCT Number(ClinicalTrials.gov Identfier)NCT03833661
2019-03-01 - 2022-12-12
Phase II
Terminated3
ICD-10C24.9
Malignant neoplasm of biliary tract, unspecified
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
-
Trial Applicant
IQVIA RDS Taiwan Ltd.
-
Sponsor
Merck KGaA
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Nai-Jung Chiang 未分科
- 姜乃榕 國衛院
- Shang-Yin Wu Division of Hematology & Oncology
- Li-Tzong Chen 國衛院
- Yan-Shen Shan Division of General Surgery
- Hui-Jen Tsai 國衛院
- Chien-Jui Huang Digestive System Department
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- Chiun Hsu Division of Hematology & Oncology
- 呂理駿 Division of Hematology & Oncology
- Ying-Chun Shen Division of Hematology & Oncology
- Ann-Lii Cheng Division of Hematology & Oncology
- YU-YUN SHAO Division of Hematology & Oncology
- 林宗哲 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Completed
Condition/Disease
Biliary Tract Cancer
Objectives
Primary
To evaluate clinical efficacy of M7824 based on ORR
Secondary
To evaluate clinical efficacy of M7824 based on
duration of response (DOR)
To evaluate clinical efficacy of M7824 based on
durable response rate (DRR)
To evaluate clinical safety of M7824
To evaluate clinical efficacy based on
progression-free survival (PFS)
To evaluate ORR, DOR, DRR, and PFS by
Investigator read
To evaluate clinical efficacy based on overall
survival (OS)
To characterize the pharmacokinetic (PK)
profile of M7824
To characterize the immunogenicity of M7824
To evaluate clinical efficacy of M7824 based on
ORR, DOR and DRR according to programmed
death ligand 1 (PD-L1) expression and
microsatellite instability (MSI) status
retrospectively
Test Drug
M7824
Active Ingredient
M7824
Dosage Form
Concentrate for solution for infusion
Dosage
10 mg/mL
Endpoints
Confirmed objective response (OR) according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) assessed by an Independent Review Committee (IRC)
Inclution Criteria
Age
1. Are ≥ 18 years of age at the time of signing the informed consent. In Japan, if a participant
is at least 18 but < 20 years of age, written informed consent from his/her parent or
guardian will be required in addition to the participant’s written consent.
Type of Participant and Disease Characteristics
2. Are participants with histologically or cytologically confirmed locally advanced or
metastatic BTC.
3. Availability of tumor (primary or metastatic) archival material or fresh biopsies (collected
within 28 days before first administration) of study intervention is mandatory. Fine needle
aspirates, transductal aspirates, or cell blocks are not acceptable. Endoscopic retrograde
cholangiography or intraductal ultrasounds assisted biopsy is acceptable, needle or
excisional biopsies, or resected tissue, are preferable. Tumor biopsies and tumor archival
material must be suitable for biomarker assessment as described in the Laboratory
Manual.
4. Participants with BTC must have failed or be intolerant to 1L systemic platinum-based
chemotherapy. Participants who received adjuvant platinum-based chemotherapy and had
evidence of disease recurrence within 6 months of completion of the adjuvant treatment
are also eligible. If recurrence occurs during or within 6 months after the adjuvant
chemotherapy, adjuvant platinum-based chemotherapy is counted as 1L chemotherapy.
5. Disease must be measurable with at least 1 unidimensionally measurable lesion by
RECIST 1.1 and verified independently by an Independent Review Committee (IRC).
6. Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1 at study entry and Day 1 of
treatment with M7824.
7. Life expectancy ≥ 12 weeks as judged by the Investigator.
8. Curatively-treated cancers with no recurrence in > 3 years or early cancers treated with
curative intent, including cervical carcinoma in situ, superficial, noninvasive bladder
cancer, or basal cell or squamous cell carcinoma in situ. Endoscopically resected early gastrointestinal (GI) cancers limited in mucosal layer (esophageal, gastric, and colorectal)
that are without recurrence in > 1 year are allowed. Other previous and/or intercurrent
cancers will be excluded.
9. Adequate hematological function defined by white blood cell (WBC) count ≥ 3 × 109
/L
with absolute neutrophil count (ANC) ≥ 1.5 × 109
/L, lymphocyte count ≥ 0.5 × 109
/L,
platelet count ≥ 75 × 109
/L, and hemoglobin (Hgb) ≥ 9 g/dL (in absence of blood
transfusion).
10. 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.
11. Adequate coagulation function defined as prothrombin time (PT) or international
normalized ratio (INR) ≤ 1.5 × ULN unless the participant is receiving anticoagulant
therapy.
12. Albumin ≥ 3.0 g/dL.
13. Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) positive participants must be
treated and on a stable dose of antivirals (e.g., entecavir, tenofovir, or lamivudine; adefovir
or interferon are not allowed) at study entry and with planned monitoring and management
including baseline HBV DNA quantity according to appropriate labeling guidance.
Participants receiving active hepatitis C virus (HCV) therapy must be on a stable dose at
study entry and with planned monitoring and management according to appropriate
labeling guidance of an approved antiviral.
14. Adequate renal function defined by either creatinine ≤ 1.5 × ULN or an estimated
creatinine clearance (CCr) > 40 mL/min according to the Cockcroft-Gault formula or by
measure of CCr from 24-hour urine collection.
CCr (mL/min) = (140-age) × weight (kg)/(72 × serum Cr jaffe)
If female, × 0.85
If Cr is measured by enzymatic method, add 0.2 and use as Crjaffe = 0.2 + Crenzume.
Sex
15. Male participants are eligible to participate if they agree to the following during the
intervention period and for at least 4 months after the last dose of study intervention:
Refrain from donating sperm
PLUS, either
Abstain from intercourse with a female
OR
Use a male condom:
When having sexual intercourse with a WOCBP, who is not currently pregnant,
and advise her to use a highly effective contraceptive method with a failure rate
of <1 % per year, as described in Appendix 3, since a condom may break or leak
When engaging in any activity that allows for exposure to ejaculate.
16. A female is eligible if she is not pregnant or breastfeeding, and at least one of the
following conditions applies:
Not a WOCBP
OR
If a WOCBP, use a highly effective contraceptive method (i.e., with a failure rate of
< 1% per year), preferably with low user dependency, as described in Appendix 3 for
the following time periods:
Before the first dose of the study intervention(s), if using hormonal contraception:
Has completed at least one 4-week cycle of an oral contraception pill and either
had or has begun her menses
OR
Has used a depot contraceptive or extended-cycle oral contraceptive for least
28 days and has a documented negative pregnancy test using a highly sensitive
assay.
During the intervention period
After the study intervention period (i.e., after the last dose of study intervention is
administered) for at least 2 months after the last dose of study intervention.
For teratogenic drugs when there is chance of DDI with hormonal contraceptive such that the
contraception may not be reliable, then an alternate method with < 1% failure rate per year
must be used.
The Investigator evaluates the effectiveness of the contraceptive method in relationship to the
first dose of study intervention.
Have a negative serum or highly sensitive urine pregnancy test, as required by local
regulations, within 24 hours before the first dose of study intervention. If a urine test
cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test
is required.
Informed Consent
17. Can give signed informed consent, as indicated in Appendix 2 (Study Governance), which
includes compliance with the requirements and restrictions listed in the informed consent
form (ICF) and this protocol.
1. Are ≥ 18 years of age at the time of signing the informed consent. In Japan, if a participant
is at least 18 but < 20 years of age, written informed consent from his/her parent or
guardian will be required in addition to the participant’s written consent.
Type of Participant and Disease Characteristics
2. Are participants with histologically or cytologically confirmed locally advanced or
metastatic BTC.
3. Availability of tumor (primary or metastatic) archival material or fresh biopsies (collected
within 28 days before first administration) of study intervention is mandatory. Fine needle
aspirates, transductal aspirates, or cell blocks are not acceptable. Endoscopic retrograde
cholangiography or intraductal ultrasounds assisted biopsy is acceptable, needle or
excisional biopsies, or resected tissue, are preferable. Tumor biopsies and tumor archival
material must be suitable for biomarker assessment as described in the Laboratory
Manual.
4. Participants with BTC must have failed or be intolerant to 1L systemic platinum-based
chemotherapy. Participants who received adjuvant platinum-based chemotherapy and had
evidence of disease recurrence within 6 months of completion of the adjuvant treatment
are also eligible. If recurrence occurs during or within 6 months after the adjuvant
chemotherapy, adjuvant platinum-based chemotherapy is counted as 1L chemotherapy.
5. Disease must be measurable with at least 1 unidimensionally measurable lesion by
RECIST 1.1 and verified independently by an Independent Review Committee (IRC).
6. Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1 at study entry and Day 1 of
treatment with M7824.
7. Life expectancy ≥ 12 weeks as judged by the Investigator.
8. Curatively-treated cancers with no recurrence in > 3 years or early cancers treated with
curative intent, including cervical carcinoma in situ, superficial, noninvasive bladder
cancer, or basal cell or squamous cell carcinoma in situ. Endoscopically resected early gastrointestinal (GI) cancers limited in mucosal layer (esophageal, gastric, and colorectal)
that are without recurrence in > 1 year are allowed. Other previous and/or intercurrent
cancers will be excluded.
9. Adequate hematological function defined by white blood cell (WBC) count ≥ 3 × 109
/L
with absolute neutrophil count (ANC) ≥ 1.5 × 109
/L, lymphocyte count ≥ 0.5 × 109
/L,
platelet count ≥ 75 × 109
/L, and hemoglobin (Hgb) ≥ 9 g/dL (in absence of blood
transfusion).
10. 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.
11. Adequate coagulation function defined as prothrombin time (PT) or international
normalized ratio (INR) ≤ 1.5 × ULN unless the participant is receiving anticoagulant
therapy.
12. Albumin ≥ 3.0 g/dL.
13. Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) positive participants must be
treated and on a stable dose of antivirals (e.g., entecavir, tenofovir, or lamivudine; adefovir
or interferon are not allowed) at study entry and with planned monitoring and management
including baseline HBV DNA quantity according to appropriate labeling guidance.
Participants receiving active hepatitis C virus (HCV) therapy must be on a stable dose at
study entry and with planned monitoring and management according to appropriate
labeling guidance of an approved antiviral.
14. Adequate renal function defined by either creatinine ≤ 1.5 × ULN or an estimated
creatinine clearance (CCr) > 40 mL/min according to the Cockcroft-Gault formula or by
measure of CCr from 24-hour urine collection.
CCr (mL/min) = (140-age) × weight (kg)/(72 × serum Cr jaffe)
If female, × 0.85
If Cr is measured by enzymatic method, add 0.2 and use as Crjaffe = 0.2 + Crenzume.
Sex
15. Male participants are eligible to participate if they agree to the following during the
intervention period and for at least 4 months after the last dose of study intervention:
Refrain from donating sperm
PLUS, either
Abstain from intercourse with a female
OR
Use a male condom:
When having sexual intercourse with a WOCBP, who is not currently pregnant,
and advise her to use a highly effective contraceptive method with a failure rate
of <1 % per year, as described in Appendix 3, since a condom may break or leak
When engaging in any activity that allows for exposure to ejaculate.
16. A female is eligible if she is not pregnant or breastfeeding, and at least one of the
following conditions applies:
Not a WOCBP
OR
If a WOCBP, use a highly effective contraceptive method (i.e., with a failure rate of
< 1% per year), preferably with low user dependency, as described in Appendix 3 for
the following time periods:
Before the first dose of the study intervention(s), if using hormonal contraception:
Has completed at least one 4-week cycle of an oral contraception pill and either
had or has begun her menses
OR
Has used a depot contraceptive or extended-cycle oral contraceptive for least
28 days and has a documented negative pregnancy test using a highly sensitive
assay.
During the intervention period
After the study intervention period (i.e., after the last dose of study intervention is
administered) for at least 2 months after the last dose of study intervention.
For teratogenic drugs when there is chance of DDI with hormonal contraceptive such that the
contraception may not be reliable, then an alternate method with < 1% failure rate per year
must be used.
The Investigator evaluates the effectiveness of the contraceptive method in relationship to the
first dose of study intervention.
Have a negative serum or highly sensitive urine pregnancy test, as required by local
regulations, within 24 hours before the first dose of study intervention. If a urine test
cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test
is required.
Informed Consent
17. Can give signed informed consent, as indicated in Appendix 2 (Study Governance), which
includes compliance with the requirements and restrictions listed in the informed consent
form (ICF) and this protocol.
Exclusion Criteria
Medical Conditions
1. Ampullary cancer is excluded.
2. Rapid clinical deterioration other than malignancy which, in the opinion of the
Investigator, may predispose to inability to tolerate treatment or study procedures.
3. Participants with active central nervous system (CNS) metastases causing clinical
symptoms or metastases that require therapeutic intervention are excluded. Participants
with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible
unless they have fully recovered from treatment, demonstrated no progression for at least
2 months, and do not require continued steroid therapy.
4. Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but
with the exception of transplants that do not require immunosuppression (e.g., corneal
transplant, hair transplant).
5. Significant acute or chronic infections, including:
Uncontrolled biliary infection. Biliary tract obstruction should be released by stenting
or percutaneous transhepatic biliary drainage.
Known history of positive test for human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome (no testing at Screening required). If an
Investigator has a strong suspicion of HIV infection without known history for a
participant in Screening, and the participant refuses testing, discuss with the Medical
Monitor to assess eligibility. (Note: HIV testing is not mandated for study inclusion;
however, if it is performed at any point in Screening or while on study, a site must
consent the participant for HIV testing as per local standard guidance.)
Active tuberculosis infection (clinical symptoms, physical or radiographic, and
laboratory findings).
Active bacterial or fungal infection requiring IV systemic therapy (except as indicated,
discuss alternative scenarios with the Medical Monitor).
6. Active autoimmune disease that might deteriorate when receiving an immunostimulatory
agent:
Participants with diabetes type 1, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid
disease not requiring immunosuppressive treatment are eligible
Participants requiring hormone replacement with corticosteroids are eligible if the
steroids are administered only for the purpose of hormonal replacement and at doses
≤ 10 mg of prednisone or equivalent per day
Administration of steroids for other conditions through a route known to result in a
minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) is
acceptable.
7. Interstitial lung disease or its history.
8. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring
hospitalization or precluding study therapy within 30 days before enrollment.
9. Known severe hypersensitivity (Grade ≥ 3 National Cancer Institute Common
Terminology Criteria for Adverse Events Version 5.0 [NCI-CTCAE 5.0]) to
investigational product (M7824) or any components in their formulations, any history of
anaphylaxis, or recent, within 5 months, history of uncontrolled asthma.
10. Persisting Grade > 1 NCI-CTCAE 5.0 toxicity (except alopecia and vitiligo) related to
prior therapy; however, sensory neuropathy Grade ≤ 2 is acceptable.
11. Clinically significant cardiovascular/cerebrovascular disease as follows: cerebral vascular
accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior
to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association
Classification Class II), or serious cardiac arrhythmia.
12. Clinically relevant diseases (e.g., inflammatory bowel disease) and/or uncontrolled
medical conditions, which, in the opinion of the Investigator, might impair the
participant’s tolerance or ability to participate in the study.
13. Any psychiatric condition that would prohibit the understanding or rendering of informed
consent.
Prior/Concomitant Therapy
14. Participants who are not eligible for or have not been treated with 1L systemic
chemotherapy will be excluded.
15. Concurrent treatment with nonpermitted drugs.
16. Prior participation in a M7824 clinical trial.
17. 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.
18. Prior therapy with any antibody or inhibitors targeting the TGF-β/TGF-β receptor
pathway.
19. Anticancer treatment within 21 days before the start of study intervention, e.g.,
cytoreductive therapy, radiotherapy involving > 30% of the bone marrow (with the
exception of palliative bone-directed radiotherapy), immune therapy, or cytokine therapy.
20. Anticancer treatment with antibody within 28 days before the start of study intervention.
21. Systemic therapy with immunosuppressive agents within 7 days before the start of study
intervention; or use of any investigational drug within 28 days before the start of study
intervention.
22. Vaccine administration within 4 weeks of M7824 administration. Vaccination with live
vaccines while on study is prohibited. Administration of inactivated vaccines is allowed
(e.g., inactivated influenza vaccines).
Prior/Concurrent Clinical Study Experience
23. Participation in experimental clinical studies after failure of 1L systemic chemotherapy.
Diagnostic Assessments
24. Unable to tolerate CT or magnetic resonance imaging (MRI) in the opinion of the
Investigator and/or allergy to contrast material.
Other Exclusions
25. Major surgery within 28 days before the start of study intervention (excluding prior
diagnostic biopsy).
26. Pregnancy or breast feeding.
27. Known active or recent alcohol or drug abuse within 2 years.
28. Legal incapacity or limited legal capacity.
29. Other severe acute or chronic medical conditions.
1. Ampullary cancer is excluded.
2. Rapid clinical deterioration other than malignancy which, in the opinion of the
Investigator, may predispose to inability to tolerate treatment or study procedures.
3. Participants with active central nervous system (CNS) metastases causing clinical
symptoms or metastases that require therapeutic intervention are excluded. Participants
with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible
unless they have fully recovered from treatment, demonstrated no progression for at least
2 months, and do not require continued steroid therapy.
4. Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but
with the exception of transplants that do not require immunosuppression (e.g., corneal
transplant, hair transplant).
5. Significant acute or chronic infections, including:
Uncontrolled biliary infection. Biliary tract obstruction should be released by stenting
or percutaneous transhepatic biliary drainage.
Known history of positive test for human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome (no testing at Screening required). If an
Investigator has a strong suspicion of HIV infection without known history for a
participant in Screening, and the participant refuses testing, discuss with the Medical
Monitor to assess eligibility. (Note: HIV testing is not mandated for study inclusion;
however, if it is performed at any point in Screening or while on study, a site must
consent the participant for HIV testing as per local standard guidance.)
Active tuberculosis infection (clinical symptoms, physical or radiographic, and
laboratory findings).
Active bacterial or fungal infection requiring IV systemic therapy (except as indicated,
discuss alternative scenarios with the Medical Monitor).
6. Active autoimmune disease that might deteriorate when receiving an immunostimulatory
agent:
Participants with diabetes type 1, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid
disease not requiring immunosuppressive treatment are eligible
Participants requiring hormone replacement with corticosteroids are eligible if the
steroids are administered only for the purpose of hormonal replacement and at doses
≤ 10 mg of prednisone or equivalent per day
Administration of steroids for other conditions through a route known to result in a
minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) is
acceptable.
7. Interstitial lung disease or its history.
8. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring
hospitalization or precluding study therapy within 30 days before enrollment.
9. Known severe hypersensitivity (Grade ≥ 3 National Cancer Institute Common
Terminology Criteria for Adverse Events Version 5.0 [NCI-CTCAE 5.0]) to
investigational product (M7824) or any components in their formulations, any history of
anaphylaxis, or recent, within 5 months, history of uncontrolled asthma.
10. Persisting Grade > 1 NCI-CTCAE 5.0 toxicity (except alopecia and vitiligo) related to
prior therapy; however, sensory neuropathy Grade ≤ 2 is acceptable.
11. Clinically significant cardiovascular/cerebrovascular disease as follows: cerebral vascular
accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior
to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association
Classification Class II), or serious cardiac arrhythmia.
12. Clinically relevant diseases (e.g., inflammatory bowel disease) and/or uncontrolled
medical conditions, which, in the opinion of the Investigator, might impair the
participant’s tolerance or ability to participate in the study.
13. Any psychiatric condition that would prohibit the understanding or rendering of informed
consent.
Prior/Concomitant Therapy
14. Participants who are not eligible for or have not been treated with 1L systemic
chemotherapy will be excluded.
15. Concurrent treatment with nonpermitted drugs.
16. Prior participation in a M7824 clinical trial.
17. 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.
18. Prior therapy with any antibody or inhibitors targeting the TGF-β/TGF-β receptor
pathway.
19. Anticancer treatment within 21 days before the start of study intervention, e.g.,
cytoreductive therapy, radiotherapy involving > 30% of the bone marrow (with the
exception of palliative bone-directed radiotherapy), immune therapy, or cytokine therapy.
20. Anticancer treatment with antibody within 28 days before the start of study intervention.
21. Systemic therapy with immunosuppressive agents within 7 days before the start of study
intervention; or use of any investigational drug within 28 days before the start of study
intervention.
22. Vaccine administration within 4 weeks of M7824 administration. Vaccination with live
vaccines while on study is prohibited. Administration of inactivated vaccines is allowed
(e.g., inactivated influenza vaccines).
Prior/Concurrent Clinical Study Experience
23. Participation in experimental clinical studies after failure of 1L systemic chemotherapy.
Diagnostic Assessments
24. Unable to tolerate CT or magnetic resonance imaging (MRI) in the opinion of the
Investigator and/or allergy to contrast material.
Other Exclusions
25. Major surgery within 28 days before the start of study intervention (excluding prior
diagnostic biopsy).
26. Pregnancy or breast feeding.
27. Known active or recent alcohol or drug abuse within 2 years.
28. Legal incapacity or limited legal capacity.
29. Other severe acute or chronic medical conditions.
The Estimated Number of Participants
-
Taiwan
20 participants
-
Global
141 participants
