A study of the investigational drug MCLA-128 which is an antibody that is specific to both HER2 and HER3 receptors that are associated with solid tumors
- Conditions
- Solid TumorsMedDRA version: 21.0Level: LLTClassification code 10049280Term: Solid tumourSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-003277-42-IT
- Lead Sponsor
- MERUS N.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 228
General Inclusion Criteria for Part 2
1. Age =18 yrs
2. =1 measurable lesion, RECIST v1.1
3. ECOG 0-1
4. life expectancy =12 wks
5. Toxicities of previous anti-cancer therapy resolved to =Gr 1, except for alopecia, lymphopenia assessed as non-clinically significant, Gr 2 sensory neurotoxicity
6. =4-wks between last radiotherapy and D1 (except =1X8 Gy for pain palliation)
7. Complete recovery from major surgery
8. Screening Labvalues:
a. 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 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 GFR of >50 mL/min Cockroft-Gault
g. Coagulation function (INR and aPTT =1.5 ULN, unless on therapeutic anticoagulants)
h. Urine protein dipstick = 2+; or =100 mg/24 hrs urine
9. Able to provide at baseline a mandatory tumor sample, 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 at Screening and =7 days of D1
11. Sexually active male and female patients of childbearing potential must agree to use an effective method of birth control during the entire study and for 6 months after final administration of MCLA-128
12. give written informed consent
13. Capable of understanding protocol requirements, is willing and able to comply with study 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
Specific Inclusion Criterion Part 2
Group A (BC) -**
15.Histologically-confirmed and documented advanced/metastatic breast cancer (BC), relapsed/refractory to =2 prior HER2 directed
regimen for breast cancer
16.Confirmed HER2 amplification (HER2 2+ by IHC confirmed by FISH, or HER2 3+ by IHC) based on historical pathology report or analysis of baseline fresh/archival tumor sample
Group B (CRC) -**
17.Histologically-confirmed and documented advanced/metastatic colorectal cancer (CRC), relapsed/refractory to at least 2 prior regimens
of standard treatments for metastatic CRC, including 1anti-EGFR treatment (if RASWT)
18.Confirmed HER2 amplification based on historical pathology report prior to commencing screening assessments
Group C (OC) -**
19.Histologically-confirmed and documented advanced/metastatic epithelial ovarian cancer (OC) for which no curative therapy is available
20.Prior therapy including all available standard therapies and =1 platinium based chemotherapy
Group D (GC or GEC)
21.Histologically-confirmed and documented advanced/metastatic gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEC)
22.Prior chemotherapy including platinium and fluoropyrimidine based treatment and trastuzumab
23.Confirmed HER2 amplification (HER2+ by IHC confirmed by FISH, or HER3+ by IHC) based on historical pathology report or analysis of fresh/archival tumor sample
Groupe E (EC)-**
24.Histologically-confirm
General Exclusion Criteria for 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. 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 halflives 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method