Overview

This is a Phase 1/2 open-label, multi-center, multi-national study with an initial dose escalation part to determine the RP2D of MCLA-158 single agent in patients with mCRC.

The dose escalation part has been completed and the RP2D will be further evaluated in an expansion part of the study. Cohorts of selected solid tumor indications for which there is evidence of EGFR dependency and potential sensitivity to EGFR inhibition will be evaluated.

The study will further assess the safety, tolerability, PK, PD, immunogenicity, and anti-tumor activity of MCLA-158.

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed solid tumors with evidence of metastatic or locally advanced disease not amenable to standard therapy with curative intent.

        HNSCC patients - Gastric/gastroesophageal junction adenocarcinoma with histologically
        confirmed EGFR amplification (FISH score EGFR/CEP7 ratio ≥2.0, or NGS EGFR copy ≥8, or
        cfDNA >2.14, or EGFR IHC H-score ≥200) - NSCLC SCC patients
          -  A baseline fresh tumor sample (FFPE) from a metastatic or primary site.
          -  Amenable for biopsy.
          -  Measurable disease as defined by RECIST version 1.1 by radiologic methods.
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
          -  Life expectancy ≥ 12 weeks, as per investigator.
          -  Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram (ECHO) or multiple
             gated acquisition scan (MUGA).
          -  Adequate organ function
        Exclusion Criteria:
          -  Central nervous system metastases that are untreated or symptomatic, or require
             radiation, surgery, or continued steroid therapy to control symptoms within 14 days of
             study entry.
          -  Known leptomeningeal involvement.
          -  Participation in another clinical trial or treatment with any investigational drug
             within 4 weeks prior to study entry.
          -  Any systemic anticancer therapy within 4 weeks or 5 half-lives whichever is longer of
             the first dose of study treatment. For cytotoxic agents that have major delayed
             toxicity ( e.g. mitomycin C,nitrosoureas), or anticancer immunotherapies, a washout
             period of 6 weeks is required.
          -  Requirement for immunosuppressive medication (e.g. methotrexate, cyclophosphamide)
          -  Major surgery or radiotherapy within 3 weeks of the first dose of study treatment.
             Patients who received prior radiotherapy to ≥25% of bone marrow are not eligible,
             irrespective of when it was received.
          -  Persistent grade >1 clinically significant toxicities related to prior antineoplastic
             therapies (except for alopecia); stable sensory neuropathy ≤ grade 2 NCI-CTCAE v4.03
             is allowed.
          -  History of hypersensitivity reaction or any toxicity attributed to human proteins or
             any of the excipients that warranted permanent cessation of these agents.
          -  Uncontrolled hypertension (systolic > 150 mmHg and/or diastolic > 100 mmHg) with
             appropriate treatment or unstable angina.
          -  History of congestive heart failure of Class II-IV New York Heart Association (NYHA)
             criteria, or serious cardiac arrhythmia requiring treatment (except atrial
             fibrillation, paroxysmal supraventricular tachycardia).
          -  History of myocardial infarction within 6 months of study entry.
          -  History of prior malignancies with the exception of excised cervical intraepithelial
             neoplasia or nonmelanoma skin cancer, or curatively treated cancer deemed at low risk
             for recurrence with no evidence of disease for at least 3 years.
          -  Current dyspnea at rest of any origin, or other diseases requiring continuous oxygen
             therapy.
          -  Patients with a history of interstitial lung disease (e.g.: pneumonitis or pulmonary
             fibrosis) or evidence of ILD on baseline chest CT scan.
          -  Current serious illness or medical conditions including, but not limited to
             uncontrolled active infection,clinically significant pulmonary, metabolic or
             psychiatric disorders.
          -  Patients with the following infectious diseases:
        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.
        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
        who 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 t the use of
        IFN-based regimens) after cessation of antiviral treatment are eligible.
          -  Patients with current cirrhotic status of Child-Pugh class B or C; known fibrolamellar
             HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
          -  Pregnant or lactating women; patients of childbearing potential must use highly
             effective contraception methods prior to study entry, for the duration of study
             participation, and for 6 months after the last dose of MCLA-158.