Solid Tumors MedDRA version: 17.1 Level: LLT Classification code 10049280 Term: Solid tumour System Organ Class: 100000004864
Conditions
Interventions
Product Name: Not available
Product Code: MCLA-128
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not assigned
CAS Number: Not assigned
Current Sponsor code: MCLA-128
Other descriptiv
Sponsors
Merus B.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: General Inclusion Criteria for Part 1 and Part 2 1. Age 18 years or older; 2. At least one measurable or evaluable disease 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 50 mL/min based on the Cockroft-Gault formula; g. Normal coagulation (elevated INR, prothrombin time or APTT 1 year ago; radiation induced oophorectomy with last menses >1 year ago; chemotherapy induced menopause with 1 year interval since last menses; 13. 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informed consent prior to any study-specific Screening procedures, with the understanding that the consent may be withdrawn by the patient at any time without prejudice; 14. 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. Specific Inclusion Criterion for Part 1 14. Histologically-confi
Exclusion criteria
Exclusion criteria: General Exclusion Criteria for Part 1 and Part 2 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. Documented symptomatic or uncontrolled intracranial or leptomeningeal metastases or primary intracerebral tumor(s); 6. 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; 7. 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; c. Treatment with chemotherapy agents within 28 days prior to the first scheduled day of dosing with MCLA-128; 8. 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; 9. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: - Determination of the MTD and/or MRD of MCLA-128 - Evaluation of adverse events (AEs) and dose limiting toxicities (DLT) Part 2 (Safety): - To characterize the safety and tolerability of MCLA-128 Part 2 (Efficacy): - Evaluation of anti-tumor response and CBR;Secondary Objective: Part 1: - To characterize the safety and tolerability of MCLA-128 - PK profile of MCLA-128 - Immunogenicity of MCLA-128 - Evaluation of anti-tumor response and CBR - Presence of biomarkers and pharmacodynamic (PD) responses to MCLA-128 Part 2: - PK profile of MCLA-128 - Immunogenicity of MCLA-128 - Evaluation of anti-tumor activity and clinical benefit - Presence of biomarkers and PD responses to MCLA-128;Primary end point(s): Part 1: - Determination of MTD/MRD and tolerability - Number and nature (severity and seriousness) of ADRs including DLTs Part 2: Primary Safety End Point: - Number and nature (severity and seriousness) of ADRs and tolerability Primary Efficacy End Point: - Proportion of patients in whom at completion of study treatment period, a CBR (PR + CR + SD) is observed, based on RECIST.;Timepoint(s) of evaluation of this end point: - Tumor assessment at Screening (up to 28 days prior to Cyc 1 D1), Cyc 2 D21; Cyc 4 D21, Cyc 5 onwards - after every 4 cyc D21, FSV, LTF - AEs recorded at Cyc 1 D1, D2 - 4, D8, D15; Cyc 2-4 D1, D8 D15, D21; Cyc 5 onwards D1, D15, D21; EOT; FSV | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1: - Number and nature (severity and seriousness) of ADRs and tolerability - PK profile of MCLA-128 - Immunogenicity of MCLA-128 - Proportion of patients in whom at completion of study treatment period, a CBR (PR + CR + SD) is observed, based on RECIST - Presence of biomarkers and pharmacodynamic (PD) responses to MCLA-128 Part 2: - PK profile of MCLA-128 - Immunogenicity of MCLA-128 - Proportion of patients in whom at completion of study treatment period, a CBR (PR + CR + SD) is observed, based on RECIST - Presence of biomarkers and PD responses to MCLA-128;Timepoint(s) of evaluation of this end point: - PK assessed at Cyc 1 D1, D2 - 4, D8, D15; Cyc 2-4 D1 - Immongenicity assessed at Cyc 1 D1; Cyc 2-4 D1; EOT; FSV - Biomarker/PD: Biopsy assessed at Screening (up to 28 days prior to Cyc 1 D1), end of Cyc 2, EOT; Blood assessed at Cyc 1 D1 (pre-dose), end of Cyc 2, EOT - Tumor assessment at Screening (up to 28 days prior to Cyc 1 D1), Cyc 2 D21; Cyc 4 D21, Cyc 5 onwards - after every 4 cyc D21, FSV, LTF - AEs recorded at Cyc 1 D1, D2 - 4, D8, D15; Cyc 2-4 D1, D8 D15, D21; Cyc 5 onwards D1, D15, D21, EOT, FSV | — |
Countries
Spain
Contacts
Public ContactMCLA-128-CL01 Project Manager
Chiltern Oncology
Outcome results
None listed