A Study of Bispecific Antibody MCLA-158 in Patients With Advanced Solid Tumors

M

Merus

Status and phase

Enrolling
Phase 2
Phase 1

Conditions

Gastric Cancer
HNSCC
Advanced/Metastatic Solid Tumors
Gastroesophageal-junction Cancer
Head and Neck Squamous Cell Carcinoma
NSCLC
Colorectal Cancer

Treatments

Combination Product: MCLA-158 +Pembrolizumab
Drug: MCLA-158

Study type

Interventional

Funder types

Other
Industry

Identifiers

NCT03526835
MCLA-158-CL01
2017-004745-24 (EudraCT Number)

Details and patient eligibility

About

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

Full description

Study Design: This open label, multicenter, first-in-human study consists of 2 parts. Part 1 is a dose escalation to find the recommended Phase II dose (RP2D) of MCLA-158 studying patients with metastatic colorectal cancer. Enrollment in the dose escalation part has been completed. Dose expansion (single-agent cohorts) In an expansion part of the study, the activity, safety, and tolerability of MCLA-158 at 1500 mg every 2 weeks (Q2W) (preliminary RP2D) as a single agent will be evaluated in cohorts of selected solid tumor indications with dependency on EGFR signaling. Eligible solid tumor indications may include locally advanced unresectable or metastatic HNSCC, gastric/gastroesophageal junction adenocarcinoma (GEA) with EGFR amplification and/or high EGFR expression, esophageal carcinoma and pancreatic adenocarcinoma. Additionally, safety will be characterized at two dose levels in this setting. Dose expansion (in combination with pembrolizumab cohort) MCLA-158 in combination with pembrolizumab will be explored first in HNSCC patients eligible to receive pembrolizumab as first-line monotherapy. Other expansion cohorts may be considered for combination treatment in the future.

Enrollment

360 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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

  • Expansion cohorts: patients with locally advanced unresectable or metastatic disease for the following indications:

    • COMBINATION FIRST-LINE HNSCC: patients eligible to receive pembrolizumab as first-line monotherapy with tumors expressing programmed cell death protein ligand 1 (PD-L1), combined positive score (CPS) ≥1, as determined by a Food and Drug Administration (FDA) approved test in the US, or by an approved equivalent test in other countries; patients should not have previous systemic therapy administered in the recurrent or metastatic setting, although previous systemic therapy as part of multimodal treatment for locally advanced disease is allowed if ended ≥6 months prior to signing the ICF. The eligible HNSCC primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx. Previous treatments with anti PD-(L)1 or anti-EGFR therapies are not allowed.

    • SINGLE AGENT SECOND-/THIRD-LINE HNSCC PATIENTS: patients who have progressed on or after, or are intolerant to, anti-PD-(L)1 therapy as monotherapy or in combination with other agents, and have progressed to a platinum-based chemotherapy less than 6 months from the last platinum dose, with no previous exposure to EGFR inhibitors. Patients with no more than 2 prior lines of treatment in recurrent or metastatic disease not amenable to standard therapy with curative intent.

      • Human papilloma virus (HPV) status determined by p16 immunohistochemistry (IHC) or molecular HPV test for all oropharyngeal tumors should be reported when available.
      • The eligible HNSCC primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.
    • GEA with histologically confirmed EGFR amplification (fluorescence in situ hybridization [FISH] score EGFR/CEP7 ratio ≥2.0, or next generation sequencing [NGS] EGFR copy ≥8, or cfDNA ≥2.5, or EGFR IHC H-score ≥200)

    • Esophageal carcinoma

    • Pancreatic adenocarcinoma

    • Patients with other indications must have been previously treated with at least 2 lines of the standard approved therapy (when applicable) in the locally advanced/unresectable or metastatic setting. Patients with malignant salivary gland tumors and squamous esophageal cancer may be enrolled after progression on 1 line of systemic standard treatment.

  • 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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

360 participants in 2 patient groups

MCLA-158
Experimental group
Description:
In Part 1, the dose escalation phase, patients with metastatic CRC will receive escalating doses of MCLA-158 (every 2 weeks) until MTD or RP2D is reached. Each Cycle is 28 days. Single agent treatment. In Part 2, the expansion phase, participants with metastatic CRC and certain other solid tumors will receive intravenous infusion of MCLA-158 at the recommended Phase II dose (RP2D) every 2 weeks, at Day 1 and Day 15. The duration of each treatment cycle is 28 days. In the expansion phase, 2 doses (1100 mg and 1500 mg) of MCLA-158 will be evaluated in a cohort of head and neck squamous cell carcinoma patients
Treatment:
Drug: MCLA-158
MCLA-158 + Pembrolizumab
Experimental group
Description:
MCLA-158 in combination with pembrolizumab will be explored first in head and neck squamous cell carcinoma patients eligible to receive pembrolizumab as first-line monotherapy.
Treatment:
Combination Product: MCLA-158 +Pembrolizumab

Trial contacts and locations

39

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Central trial contact

Ernesto Wasserman, MD; Eduardo Pennella, MD

Data sourced from clinicaltrials.gov

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