Clinical Trials List
Protocol NumberMCLA-128-CL01
NCT Number(ClinicalTrials.gov Identfier)NCT02912949
2018-04-15 - 2020-12-31
Phase I/II
Recruiting1
ICD-9199.0
Disseminated malignant neoplasm
A Phase I/II Study of MCLA-128, a Full Length IgG1 Bispecific Antibody Targeting HER2 and HER3, in Patients With Solid Tumors
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Trial Applicant
COVANCE TAIWAN SERVICES LIMITED
-
Sponsor
Merus N.V.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 徐偉勛 未分科
- Hsiang-Fong Kao 未分科
- Chong-Jen Yu Division of General Internal Medicine
- 張端瑩 未分科
- Jih-Hsiang Lee
- Chia-Chi Lin Division of Hematology & Oncology
- Kun-Huei Yeh 未分科
- SHIH-HUNG YANG 未分科
- 廖斌志 未分科
- 陳國興 未分科
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Condition/Disease
Solid tumor
Objectives
Primary: Determination of the MTD and/or MRD of MCLA-128.Secondary: To characterize the safety and tolerabilityof MCLA-128. PK profile of MCLA-128. Immunogenicity of MCLA-128. Evaluation of anti-tumor response andCBR.
Test Drug
MCLA-128
Active Ingredient
MCLA-128
Dosage Form
Solution for IV injection
Dosage
20 mg/ml, 5 ml per vial
Endpoints
Primary Outcome Measures :
Characterize the safety and tolerability of zenocutuzumab (MCLA-128) [ Time Frame: 6-12 months ]
Number of participants with Adverse Events (AE) and Serious Adverse Events (SAE)
Objective overall response rate (ORR) [ Time Frame: 36 months ]
Evaluation of clinical benefit assessed by RECIST v1.1 determining objective overall response rate (ORR)
Duration of response (DOR) [ Time Frame: 36 months ]
Evaluation of clinical benefit assessed by RECIST v1.1 determining duration of response (DOR)
Correlation of anti-tumor activity and biomarkers [ Time Frame: 36 months ]
Evaluate the correlation between the anti-tumor activity of zenocutuzumab (MCLA-128) and HER2
Correlation of anti-tumor activity and biomarkers [ Time Frame: 36 months ]
Evaluate the correlation between the anti-tumor activity of zenocutuzumab (MCLA-128) and HER3
Correlation of anti-tumor activity and biomarkers [ Time Frame: 36 months ]
Evaluate the correlation between the anti-tumor activity of zenocutuzumab (MCLA-128) and Heregulin
Correlation of anti-tumor activity and biomarkers [ Time Frame: 36 months ]
Evaluate the correlation between the anti-tumor activity of zenocutuzumab (MCLA-128) and disease related biomarkers (i.e. CA19-9)
Characterize the safety and tolerability of zenocutuzumab (MCLA-128) [ Time Frame: 6-12 months ]
Number of participants with Adverse Events (AE) and Serious Adverse Events (SAE)
Objective overall response rate (ORR) [ Time Frame: 36 months ]
Evaluation of clinical benefit assessed by RECIST v1.1 determining objective overall response rate (ORR)
Duration of response (DOR) [ Time Frame: 36 months ]
Evaluation of clinical benefit assessed by RECIST v1.1 determining duration of response (DOR)
Correlation of anti-tumor activity and biomarkers [ Time Frame: 36 months ]
Evaluate the correlation between the anti-tumor activity of zenocutuzumab (MCLA-128) and HER2
Correlation of anti-tumor activity and biomarkers [ Time Frame: 36 months ]
Evaluate the correlation between the anti-tumor activity of zenocutuzumab (MCLA-128) and HER3
Correlation of anti-tumor activity and biomarkers [ Time Frame: 36 months ]
Evaluate the correlation between the anti-tumor activity of zenocutuzumab (MCLA-128) and Heregulin
Correlation of anti-tumor activity and biomarkers [ Time Frame: 36 months ]
Evaluate the correlation between the anti-tumor activity of zenocutuzumab (MCLA-128) and disease related biomarkers (i.e. CA19-9)
Inclution Criteria
1. Age 18 years or older;
2. At least one measurable lesion according to RECIST v1.1;
3. Performance status of ECOG 0 or 1;
4. Estimated life expectancy of at least 12 weeks;
5. Toxicities incurred as a result of previous anti-cancer therapy resolved to ≤Grade 1 (as
defined by NCI CTCAE v4.03), except for alopecia, lymphopenia assessed as non-clinically
significant, Grade 2 sensory neurotoxicity;
6. At least a 4-week interval between the last received radiotherapy and the first scheduled day
of dosing with MCLA-128 (with the exception of up to 1x8 Gy for pain palliation);
7. Complete recovery from major surgery (stable and
a. Absolute neutrophil count ≥1.5 x 109
/L without colony stimulating factor support;
b. Platelets ≥100 x 109
/L;
c. Hemoglobin ≥9 g/dL or ≥2.2 mmol/L (not transfusion dependent);
d. Total bilirubin <1.5 times the upper limit of normal (ULN) (unless due to Gilbert’s
syndrome);
e. AST (SGOT) ≤2.5 x ULN; ALT (SGPT) ≤2.5 x ULN; ≤5 x ULN for patients with
advanced solid tumors with liver metastases; patients with confirmed bony metastases
will be permitted on study with isolated elevations in ALP >5 x ULN;
f. Serum creatinine 1.5 x ULN or estimated glomerular filtration rate (GFR) of >50
mL/min based on the Cockroft-Gault formula;
g. Coagulation function (INR and aPTT ≤1.5 ULN, unless on therapeutic anticoagulants)
h. Urine protein ≤ 2+ (as measured by dipstick) or ≤100 mg/24 hours urine;
9. Able to provide at baseline a mandatory tumor biopsy sample (FFPE), preferably a block,
from fresh (preferred) or archival tissue. Archival tissue must be collected within 2 years
before screening, other than for NSCLC which must be within 1 year;
10. Negative pregnancy test results available as defined by urine or blood human chorionic
gonadotropin (hCG) test during Screening and within 7 days of Cycle 1, Day 1 in women of
childbearing potential (defined as women ≤50 years of age or history of amenorrhea for ≤12
months prior to study entry);
11. Sexually active male and female patients of childbearing potential must agree to use an
effective method of birth control (e.g., barrier methods with spermicides, oral or parenteral
contraceptives and/or intrauterine devices) during the entire duration of the study and for 6
months after final administration of MCLA-128. Note that sterility in female patients must
be confirmed in the patients’ medical records and be defined as any of the following:
surgical hysterectomy with bilateral oophorectomy, bilateral tubular ligation, natural
menopause with last menses >1 year ago; radiation induced oophorectomy with last menses
>1 year ago; chemotherapy induced menopause with 1 year interval since last menses;
12. Ability to give written, informed consent prior to any study-specific Screening procedures,
with the understanding that the consent may be withdrawn by the patient at any time without
prejudice;
13. Capable of understanding the mandated and optional protocol requirements, is willing and
able to comply with the study protocol procedures and has signed the main informed consent
document. For any optional biopsy sampling (tissue and/or blood) and long-term sample
storage, additional consent is required;
14. Patient with metastatic cancer who has disease progression after having received treatment
with all available therapies known to convey clinical benefit.
2. At least one measurable lesion according to RECIST v1.1;
3. Performance status of ECOG 0 or 1;
4. Estimated life expectancy of at least 12 weeks;
5. Toxicities incurred as a result of previous anti-cancer therapy resolved to ≤Grade 1 (as
defined by NCI CTCAE v4.03), except for alopecia, lymphopenia assessed as non-clinically
significant, Grade 2 sensory neurotoxicity;
6. At least a 4-week interval between the last received radiotherapy and the first scheduled day
of dosing with MCLA-128 (with the exception of up to 1x8 Gy for pain palliation);
7. Complete recovery from major surgery (stable and
a. Absolute neutrophil count ≥1.5 x 109
/L without colony stimulating factor support;
b. Platelets ≥100 x 109
/L;
c. Hemoglobin ≥9 g/dL or ≥2.2 mmol/L (not transfusion dependent);
d. Total bilirubin <1.5 times the upper limit of normal (ULN) (unless due to Gilbert’s
syndrome);
e. AST (SGOT) ≤2.5 x ULN; ALT (SGPT) ≤2.5 x ULN; ≤5 x ULN for patients with
advanced solid tumors with liver metastases; patients with confirmed bony metastases
will be permitted on study with isolated elevations in ALP >5 x ULN;
f. Serum creatinine 1.5 x ULN or estimated glomerular filtration rate (GFR) of >50
mL/min based on the Cockroft-Gault formula;
g. Coagulation function (INR and aPTT ≤1.5 ULN, unless on therapeutic anticoagulants)
h. Urine protein ≤ 2+ (as measured by dipstick) or ≤100 mg/24 hours urine;
9. Able to provide at baseline a mandatory tumor biopsy sample (FFPE), preferably a block,
from fresh (preferred) or archival tissue. Archival tissue must be collected within 2 years
before screening, other than for NSCLC which must be within 1 year;
10. Negative pregnancy test results available as defined by urine or blood human chorionic
gonadotropin (hCG) test during Screening and within 7 days of Cycle 1, Day 1 in women of
childbearing potential (defined as women ≤50 years of age or history of amenorrhea for ≤12
months prior to study entry);
11. Sexually active male and female patients of childbearing potential must agree to use an
effective method of birth control (e.g., barrier methods with spermicides, oral or parenteral
contraceptives and/or intrauterine devices) during the entire duration of the study and for 6
months after final administration of MCLA-128. Note that sterility in female patients must
be confirmed in the patients’ medical records and be defined as any of the following:
surgical hysterectomy with bilateral oophorectomy, bilateral tubular ligation, natural
menopause with last menses >1 year ago; radiation induced oophorectomy with last menses
>1 year ago; chemotherapy induced menopause with 1 year interval since last menses;
12. Ability to give written, informed consent prior to any study-specific Screening procedures,
with the understanding that the consent may be withdrawn by the patient at any time without
prejudice;
13. Capable of understanding the mandated and optional protocol requirements, is willing and
able to comply with the study protocol procedures and has signed the main informed consent
document. For any optional biopsy sampling (tissue and/or blood) and long-term sample
storage, additional consent is required;
14. Patient with metastatic cancer who has disease progression after having received treatment
with all available therapies known to convey clinical benefit.
Exclusion Criteria
1. Pregnant or lactating;
2. Presence of an active infection or an unexplained fever greater than 38.5°C during Screening
up to the first scheduled day of dosing. At the discretion of the Investigator, patients with
tumor fever may be enrolled;
3. Known hypersensitivity to any of the components of MCLA-128 or history of severe
hypersensitivity reactions to human or humanized monoclonal antibodies, including
therapeutic antibodies;
4. Known HIV, Hepatitis B or Hepatitis C; patients who have previously been treated for
Hepatitis C and have undetectable viral loads are eligible;
5. Any untreated central nervous system (CNS) lesion. However, patients are eligible if: a) all
known CNS lesions have been treated with radiotherapy and/or surgery and b) patient
remained without evidence of CNS disease progression ≥ 4 weeks after treatment and c)
patients must be off corticosteroid therapy for ≥ 3 weeks;
6. Patients with leptomeningeal metastases;
7. Previous or concurrent malignancy (excluding non-basal cell carcinoma of skin or carcinoma
in situ of the uterine cervix) unless the tumor was treated with curative intent more than 2
years prior to study entry;
8. Prior anti-tumor therapy including:
a. Approved anti-HER2 therapies and/or anti-EGFR approved therapies within 28 days
prior to the first scheduled day of dosing with MCLA-128;
b. Investigational therapy administered within 28 days prior to the first scheduled day of
dosing with MCLA-128. Dosing with MCLA-128 within 28 days of receiving
investigational therapy is acceptable once a time interval equal to at least five half-lives
of the investigational agent has passed or in case of prior checkpoint inhibitory
treatment;
c. Treatment with chemotherapy agents within 28 days prior to the first scheduled day of
dosing with MCLA-128;
9. Presence of NYHA Class III or IV congestive heart failure or LVEF <50% or history of
significant cardiac disease, unstable angina, congestive heart failure, myocardial infarction,
or ventricular arrhythmia requiring medication;
10. Presence of any other medical or psychological condition deemed by the Investigator to be
likely to interfere with a patient's ability to sign informed consent, cooperate or participate in
the study, or interfere with the interpretation of the results.
2. Presence of an active infection or an unexplained fever greater than 38.5°C during Screening
up to the first scheduled day of dosing. At the discretion of the Investigator, patients with
tumor fever may be enrolled;
3. Known hypersensitivity to any of the components of MCLA-128 or history of severe
hypersensitivity reactions to human or humanized monoclonal antibodies, including
therapeutic antibodies;
4. Known HIV, Hepatitis B or Hepatitis C; patients who have previously been treated for
Hepatitis C and have undetectable viral loads are eligible;
5. Any untreated central nervous system (CNS) lesion. However, patients are eligible if: a) all
known CNS lesions have been treated with radiotherapy and/or surgery and b) patient
remained without evidence of CNS disease progression ≥ 4 weeks after treatment and c)
patients must be off corticosteroid therapy for ≥ 3 weeks;
6. Patients with leptomeningeal metastases;
7. Previous or concurrent malignancy (excluding non-basal cell carcinoma of skin or carcinoma
in situ of the uterine cervix) unless the tumor was treated with curative intent more than 2
years prior to study entry;
8. Prior anti-tumor therapy including:
a. Approved anti-HER2 therapies and/or anti-EGFR approved therapies within 28 days
prior to the first scheduled day of dosing with MCLA-128;
b. Investigational therapy administered within 28 days prior to the first scheduled day of
dosing with MCLA-128. Dosing with MCLA-128 within 28 days of receiving
investigational therapy is acceptable once a time interval equal to at least five half-lives
of the investigational agent has passed or in case of prior checkpoint inhibitory
treatment;
c. Treatment with chemotherapy agents within 28 days prior to the first scheduled day of
dosing with MCLA-128;
9. Presence of NYHA Class III or IV congestive heart failure or LVEF <50% or history of
significant cardiac disease, unstable angina, congestive heart failure, myocardial infarction,
or ventricular arrhythmia requiring medication;
10. Presence of any other medical or psychological condition deemed by the Investigator to be
likely to interfere with a patient's ability to sign informed consent, cooperate or participate in
the study, or interfere with the interpretation of the results.
The Estimated Number of Participants
-
Taiwan
10 participants
-
Global
430 participants
