Clinical Trials List
Protocol NumberMS200647-0008
NCT Number(ClinicalTrials.gov Identfier)NCT02699515
2016-07-01 - 2019-12-31
Phase I
Terminated5
ICD-10C80.1
Malignant (primary) neoplasm, unspecified
A Phase I, open-label, multiple-ascending dose trial to investigate the safety, tolerability, pharmacokinetics, biological and clinical activity of MSB0011359C (M7824) in subjects with metastatic or locally advanced solid tumors with expansion to selected indications in Asia
-
Trial Applicant
IQVIA RDS Taiwan Ltd.
-
Sponsor
Merck KGaA
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Nai-Jung Chiang Division of Hematology & Oncology
- Shang-Hung Chen Division of Hematology & Oncology
- 姜乃榕 Division of Hematology & Oncology
- Yan-Shen Shan Division of General Surgery
- Hui-Jen Tsai Division of Hematology & Oncology
- Chia-Jui Yen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Linkou Chang Gung Medical Foundation
Taiwan National PI
侯明模
Co-Principal Investigator
- Wen-Chi Chou Division of Hematology & Oncology
- Jen-Shi Chen Division of Hematology & Oncology
- Hsien-Kun Chang Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
4 Stop recruiting
Audit
CRO
Co-Principal Investigator
- TA-CHEN HUANG Division of Hematology & Oncology
- SHIH-HUNG YANG Division of Hematology & Oncology
- Kun-Huei Yeh Division of Hematology & Oncology
- 陳國興 Division of Hematology & Oncology
- Chih-Hung Hsu Division of Hematology & Oncology
- SHIH-HUNG YANG Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
metastatic or locally advanced solid tumors
Objectives
Primary Objective
The primary objective of the trial is to determine the safety, tolerability and MTD administered as
monotherapy of MSB0011359C in subjects with metastatic or locally advanced solid tumors.
Secondary Objective
The secondary objectives are:
To characterize the PK profile of MSB0011359C
To evaluate the immunogenicity of MSB0011359C and its relationship to drug exposure
To assess the best overall response (BOR) according to RECIST 1.1
Exploratory Objectives
To assess progression-free survival time (PFS) according to RECIST 1.1
To characterize OS time
To assess the immune-related BOR (irBOR) using the modified immune-related response
criteria (irRC), derived from RECIST 1.1 (see Section 7.3.1)
To assess immune-related PFS (irPFS) using irRC
To evaluate biological response or predictive markers in blood, tumor, and tumor environment
and their relationships to drug exposure, clinical response, or other biologic response markers
To assess BOR in subjects with HCC using mRECIST
Test Drug
MSB0011359C (M7824)
Active Ingredient
MSB0011359C
Dosage Form
Powder for Concentrate for Solution for Infusion
Dosage
45 mg/vial
Endpoints
Primary endpoints:
The primary endpoints for the dose escalation part of the trial are:
Occurrence of DLTs during the first 3 weeks (21 days) of treatment in the dose escalation
part
Number, severity and duration of treatment-emergent AEs (TEAEs) according to the
National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events
version 4.03 (CTCAE v4.03)
Number, severity, and duration of treatment-related AEs for all dose groups/indications
according to CTCAE v4.03.
The primary endpoints for the dose escalation part of the trial are:
Occurrence of DLTs during the first 3 weeks (21 days) of treatment in the dose escalation
part
Number, severity and duration of treatment-emergent AEs (TEAEs) according to the
National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events
version 4.03 (CTCAE v4.03)
Number, severity, and duration of treatment-related AEs for all dose groups/indications
according to CTCAE v4.03.
Inclution Criteria
Key inclusion criteria for the dose escalation include:
1. Able and willing to give written informed consent and has signed the appropriate written
informed consent form (ICF), prior to performance of any trial activities.
2. Eligible male and female subjects aged ≥20 years.
3. Histologically or cytologically proven metastatic or locally advanced solid tumors, for
which no effective standard therapy exists or standard therapy has failed.
4. ECOG performance status of 0 to 1 at trial entry.
5. Life expectancy ≥12 weeks as judged by the Investigator.
6. 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 Hgb ≥ 9 g/dL (in absence of blood transfusion).
7. Adequate hepatic function defined by a total bilirubin level ≤1.5 × ULN, an AST level
≤ 2.5 × ULN, and an ALT level ≤ 2.5 × ULN.
8. Adequate renal function defined by an estimated creatinine clearance >50 mL/min
according to the Cockcroft-Gault formula or by measure of creatinine clearance from
24-hour urine collection.
Key inclusion criteria for the expansion cohorts are:
1. Able and willing to give written informed consent and has signed the appropriate written
ICF, prior to performance of any trial activities.
2. Eligible male or female subjects aged ≥20 years.
3. Subjects must have one of the following:
GC: Histologically or cytologically confirmed recurrent or refractory unresectable
stage IV gastric or gastro-esophageal junctional adenocarcinoma (according to
American Joint Committee on Cancer/Union Internationale Contre le Cancer 7th
edition) for which no standard therapy exists or standard therapy has failed.
ESCC: Histologically or cytologically confirmed esophageal squamous cell cancer for
which no standard therapy exists or standard therapy has failed.
BTC: Histologically or cytologically confirmed biliary tract cancer for which no
standard therapy exists or standard therapy has failed.
HCC, second line or sorafenib intolerant: Histologically confirmed HCC. Must be
unresectable or have advanced disease not amenable to curative resection. Must have
had progression following 1 line of prior sorafenib therapy (must have received at least
14 days of sorafenib at least 400 mg per day) or previously considered to be sorafenib
intolerant.
Additional inclusion criteria for HCC subjects include subjects with no allergies to
contrast and able to tolerate computed tomography (CT) or magnetic resonance imaging
(MRI) contrast in the opinion of the Investigator.
4. Availability of tumor (primary or metastatic) archival material or fresh biopsies within
28 days before first administration of IMP is mandatory.
5. Disease must be measurable with at least 1 unidimensional measureable lesion by
RECIST 1.1.
6. Subjects may be on a stable bisphosphonate dose provided it has not been initiated within
14 days of receiving the first administration of MSB0011359C.
1. Able and willing to give written informed consent and has signed the appropriate written
informed consent form (ICF), prior to performance of any trial activities.
2. Eligible male and female subjects aged ≥20 years.
3. Histologically or cytologically proven metastatic or locally advanced solid tumors, for
which no effective standard therapy exists or standard therapy has failed.
4. ECOG performance status of 0 to 1 at trial entry.
5. Life expectancy ≥12 weeks as judged by the Investigator.
6. 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 Hgb ≥ 9 g/dL (in absence of blood transfusion).
7. Adequate hepatic function defined by a total bilirubin level ≤1.5 × ULN, an AST level
≤ 2.5 × ULN, and an ALT level ≤ 2.5 × ULN.
8. Adequate renal function defined by an estimated creatinine clearance >50 mL/min
according to the Cockcroft-Gault formula or by measure of creatinine clearance from
24-hour urine collection.
Key inclusion criteria for the expansion cohorts are:
1. Able and willing to give written informed consent and has signed the appropriate written
ICF, prior to performance of any trial activities.
2. Eligible male or female subjects aged ≥20 years.
3. Subjects must have one of the following:
GC: Histologically or cytologically confirmed recurrent or refractory unresectable
stage IV gastric or gastro-esophageal junctional adenocarcinoma (according to
American Joint Committee on Cancer/Union Internationale Contre le Cancer 7th
edition) for which no standard therapy exists or standard therapy has failed.
ESCC: Histologically or cytologically confirmed esophageal squamous cell cancer for
which no standard therapy exists or standard therapy has failed.
BTC: Histologically or cytologically confirmed biliary tract cancer for which no
standard therapy exists or standard therapy has failed.
HCC, second line or sorafenib intolerant: Histologically confirmed HCC. Must be
unresectable or have advanced disease not amenable to curative resection. Must have
had progression following 1 line of prior sorafenib therapy (must have received at least
14 days of sorafenib at least 400 mg per day) or previously considered to be sorafenib
intolerant.
Additional inclusion criteria for HCC subjects include subjects with no allergies to
contrast and able to tolerate computed tomography (CT) or magnetic resonance imaging
(MRI) contrast in the opinion of the Investigator.
4. Availability of tumor (primary or metastatic) archival material or fresh biopsies within
28 days before first administration of IMP is mandatory.
5. Disease must be measurable with at least 1 unidimensional measureable lesion by
RECIST 1.1.
6. Subjects may be on a stable bisphosphonate dose provided it has not been initiated within
14 days of receiving the first administration of MSB0011359C.
Exclusion Criteria
Key exclusion criteria
1. Concurrent treatment with non-permitted drugs.
2. Prior therapy with any antibody/drug targeting T cell coregulatory proteins (immune
checkpoints) such as anti-PD-1, anti-PD-L1, anti-cytotoxic T lymphocyte antigen-4
(CTLA-4) antibody (consult Medical Monitor if necessary), or anti-4-1BB antibody, is not
allowed (consult with Medical Monitor as needed), inclusive of intrahepatic, localized
administration of such agents.
3. Prior therapy with any antibody/drug targeting TGFβ or TGF receptor.
4. Anticancer treatment within 21 days before the start of trial treatment, eg, cytoreductive
therapy, radiotherapy (with the exception of palliative bone-directed radiotherapy), immune
therapy, or cytokine therapy.
5. Anticancer treatment with antibody within 28 days before the start of trial treatment.
6. Major surgery within 28 days before the start of trial treatment (excluding prior diagnostic
biopsy).
7. Systemic therapy with immunosuppressive agents within 7 days before the start of trial
treatment; or use of any investigational drug within 28 days before the start of trial
treatment.
1. Concurrent treatment with non-permitted drugs.
2. Prior therapy with any antibody/drug targeting T cell coregulatory proteins (immune
checkpoints) such as anti-PD-1, anti-PD-L1, anti-cytotoxic T lymphocyte antigen-4
(CTLA-4) antibody (consult Medical Monitor if necessary), or anti-4-1BB antibody, is not
allowed (consult with Medical Monitor as needed), inclusive of intrahepatic, localized
administration of such agents.
3. Prior therapy with any antibody/drug targeting TGFβ or TGF receptor.
4. Anticancer treatment within 21 days before the start of trial treatment, eg, cytoreductive
therapy, radiotherapy (with the exception of palliative bone-directed radiotherapy), immune
therapy, or cytokine therapy.
5. Anticancer treatment with antibody within 28 days before the start of trial treatment.
6. Major surgery within 28 days before the start of trial treatment (excluding prior diagnostic
biopsy).
7. Systemic therapy with immunosuppressive agents within 7 days before the start of trial
treatment; or use of any investigational drug within 28 days before the start of trial
treatment.
The Estimated Number of Participants
-
Taiwan
16 participants
-
Global
117 participants
