Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at La Jolla, California and other locations
Dates
study started
completion around
Principal Investigator
by Shumei Kato, MD
Headshot of Shumei Kato
Shumei Kato

Description

Summary

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.

Official Title

Phase 1/2 Dose Escalation and Cohort Expansion Study Evaluating Single-agent MCLA-158 in Metastatic Colorectal Cancer and Other Advanced Solid Tumors

Details

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. Part 2 is a dose expansion cohort studying MCLA-158 in colorectal cancer and other solid tumor indications.

In the dose escalation part, patients with metastatic colorectal cancer previously treated with up to 4 lines of prior therapy in the metastatic setting (including oxaliplatin-based and irinotecan-based chemotherapy, with or without an anti-angiogenic and with or without an anti-EGFR if RAS wild-type (RASwt)) were treated. The dose escalation part has been completed and the RP2D will be further evaluated in the expansion part of the study.

In the expansion part, MCLA-158 will be administered at the RP2D in metastatic colorectal patients and selected non-colorectal indications in advanced solid tumors. The expansion part will further characterize the safety, PK, immunogenicity and preliminary antitumor activity of single-agent MCLA-158 will be in all patients, and retrospective biomarker analyses including EGFR and LGR5 status will be performed.

The study consists of three periods: Screening (up to 28 days prior to the first dose of study drug); Treatment (first dose of study drug with treatment cycles of 28 days); and Follow-up (through 30 days after the last dose and and quarterly checks for survival data up to 12 months).

Keywords

Advanced/Metastatic Solid Tumors, Colorectal Cancer, Gastric Cancer, Gastroesophageal-junction Cancer, NSCLC, HNSCC, Bispecific antibody, First-in-human, MCLA-158, Antibodies, Bispecific, immunologic factors, Cytokines, EGFR, LGR5, Colorectal Neoplasms

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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

You CAN'T join if...

  • 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.

Locations

  • UCSD accepting new patients
    La Jolla California 92093 United States
  • Sarah Cannon Research Institute completed
    Nashville Tennessee 37203 United States
  • Cambridge University Hospitals NHS Foundation Trust accepting new patients
    Cambridge United Kingdom
  • Sarah Cannon Research Institute accepting new patients
    London United Kingdom

Lead Scientist at UCSD

  • Shumei Kato, MD
    Associate Clinical Professor, Medicine, Vc-health Sciences-schools. Authored (or co-authored) 94 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Merus N.V.
ID
NCT03526835
Phase
Phase 1/2 research study
Study Type
Interventional
Participants
Expecting 360 study participants
Last Updated