A study of the investigational drug MCLA-128 which is an antibody that isspecific to both HER2 and HER3 receptors that are associated with solidtumors

Phase 1

Conditions: Solid Tumors
MedDRA version: 19.0Level: LLTClassification code 10049280Term: Solid tumourSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-003277-42-FR

Lead Sponsor: Merus N.V.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 120

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 8. Laboratory values at Screening:
a. Absolute neutrophil count =1.5 x 10e9/L without colony stimulating factor support;
b. Platelets =100 x 10e9/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. Normal coagulation (elevated INR, prothrombin time or APTT <1.3 x ULN acceptable);
h. Urine protein = 2+ (as measured by dipstick);) or =100 mg/24 hours urine
9. Able to provide an archival tumor biopsy sample or provision of consent to obtain fresh sample at Screening;
10. Candidate patients with metastatic colorectal cancer, should have availability of a pathology report indicating mutational status of KRAS, NRAS, PIK3CA and BRAF” or provision of consent to obtain fresh biopsy sample at Screening;
11. 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);
12. 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;
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 Par

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.