metastatic epithelial tumours solid tumours
Conditions
Interventions
For part 2:
For protocol v3.0 the maximum tolerated dose was determined to be 750mg.
IV MCLA-128 (infusion time 120 minutes) will be dispensed to the patients on
the first day of every cycle.
Every
Sponsors
Merus N.V.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Age 18 years or older; 2. At least one measurable lesion according to RECIST v1.1 OR evaluable disease for a limited number of patients (up to 15) in Group H; 3. Performance status of ECOG 0, 1 or 2; 4. Estimated life expectancy of at least 12 weeks; 5. Toxicities incurred as a result of previous anti-cancer therapy resolved to 14 days or >5 half-lives prior to study entry, whichever is shorter. b. >14 days for radiotherapy. Note: A less than 1-week wash-out period is permitted only for palliative radiation to non-CNS disease with Sponsor approval. 7. Patient has recovered from prior surgery or other procedure or complication to =1.5 x 109/L without colony stimulating factor support for at least 7 days prior to screening; b. Platelets >=75 x 109/L without transfusion support for at least 7 days prior to screening; c. Hemoglobin >=8 g/dL or >=5 mmol/L; d. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) 3x ULN in the absence of underlying liver disease may be considered for enrollment upon Sponsor review and approval; in cases of antecedents of Gilbert*s syndrome when total bilirubin 30 mL/min based on the Cockroft-Gault formula; 9. Able to provide at baseline a mandatory tumor biopsy sample (FFPE), preferably a block. If safe/feasible, a fresh FFPE biopsy sample is preferred; archival tissue is acceptable (preferably not more than 2 years old); NOTE1: For patients who received afatinib or other HER-targeting agents, a biopsy collected after the last line of treatment is strongly preferred to assess for mechanisms of acquired resistance. NOTE2:For patients with a locally confirmed NRG1 gene fusion, when archival tissue is not available and collection of a fresh biopsy is not safe or feasible during the screening period, these patients will be allowed to enroll in the MCLA-128-CL01 trial provided they meet all other inclusion/exclusion criteria. 10. Negative pregnancy test during Screening and within 7 days of Cycle 1; NOTE: Women with amenorrhea associated with prior treatment with antineoplastic medications are still considered as being of child-bearing potential. 11. Sexually active male and female patients of childbearing potential must agree to use one of the highly effective methods of birth control during the entire duration of the study and for 6 months after final administration of MCLA-128. 12. Ability to give written, informed consent prior to
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating; 2. Presence of an active uncontrolled 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 or a clinically insignificant minor infection may be enrolled (i.e. mild upper respiratory infection); 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. Patients with the following infectious diseases are excluded: a. known HIV b. active Hepatitis B infection (HBsAg positive) without receiving antiviral treatment Note: • Patients with active hepatitis B (HBsAg positive) must receive antiviral treatment with lamivudine, tenofovir, entecavir, or other antiviral agents, starting at least >= 7 days before the initiation of the study treatment. • Patients with antecedents of Hepatitis B (anti-HBc positive, HBsAg and HBV-DNA negative) are eligible. c. positive test for Hepatitis C ribonucleic acid (HCV RNA) Note: Patients in whom HCV infection resolved spontaneously (positive HCV antibodies without detectable HCV-RNA) or those that achieved a sustained response after antiviral treatment and show absence of detectable HCV RNA >= 6 months (with the use of IFN-free regimens) or >= 12 months (with the use of IFN-based regimens) after cessation of antiviral treatment are eligible; NOTE: Patients without known or suspected HIV, Hepatitis B or Hepatitis C infection do not require specific viral testing during the screening period. 5. Known symptomatic or unstable brain metastases. Patients with asymptomatic brain metastases are eligible to participate if the metastases have been radiographically and clinically stable for at least one month. If on steroids for this indication, the patient must be on a stable dose for at least one month. 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 or palliative intent and in the opinion of the investigator, with sponsor agreement, the previous or concurrent malignancy condition doesn*t affect the assessment of safety and efficacy of the study drug; 9. Presence of LVEF
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 2 of the study: The determination of the safety and tolerability of MCLA-128 by the frequency and nature of the adverse events and to explore the anti-tumour activity of MCLA128 and disease related biomarkers. | — |
Secondary
| Measure | Time frame |
|---|---|
| Part 2 of the study: PK profile - total exposure, maximum concentration, clearance, volume distribution, half-life and AUC of MCLA-128. Immunogenicity - incidence and serumtiters of anti-drug antibodies against MCLA-128. Evaluation of PFS and overall survival, duration of response Exploratory - Assessment of other relevant tumor biomarkers and markers of MCLA-128 activity in archival and/or fresh tumor sample/biopsy material and blood. (see protocol for details). | — |
Countries
Netherlands
Outcome results
None listed