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

• Status: Unknown status
• Trial end date: 2021-01-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase I, open-label, multi-center, multi-national, dose escalation, single agent study to determine the recommended Phase II dose (RP2D) of MCLA-158 in metastatic colorectal cancer (mCRC). The study will assess the safety, tolerability, PK, PD, immunogenicity, and anti-tumor activity of MCLA-158 in mCRC and other advanced solid tumors.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Merus N.V.
• Collaborators: 4Clinics; Chiltern International Inc.; Oncology Therapeutic Development (OTD); Q2 Solutions
• Treatments: Antibodies; Antibodies, Bispecific; Immunoglobulins

Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed solid tumors with evidence of metastatic or locally disease not amenable to standard therapy with curative intent with patients with metastatic colorectal cancer treated in the metastatic setting with standard approved therapy including oxaliplatin, irinotecan and fluoropyrimidines (5-FU and/or capecitabine) ± an anti-angiogenic agent ± an anti-EGFR agent.

• A baseline fresh tumor sample (FFPE and if sufficient material also frozen) from a metastatic or primary site.

• 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.

• 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.

• Active HIV, HBV, or HCV infection requiring specific treatment.

• 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.