Clinical Trials /

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

NCT03526835

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Bispecific Antibody MCLA-158 in Patients With Advanced Solid Tumors
  • Official Title: Phase 1 Dose Finding Study Evaluating the Bispecific Antibody MCLA-158 in Metastatic Colorectal Cancer and Other Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: MCLA-158-CL01
  • SECONDARY ID: 2017-004745-24
  • NCT ID: NCT03526835

Conditions

  • Advanced/Metastatic Solid Tumors
  • Colorectal Cancer

Interventions

DrugSynonymsArms
MCLA-158bispecificMCLA-158

Purpose

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.

Detailed 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. 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).

      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).
    

Trial Arms

NameTypeDescriptionInterventions
MCLA-158ExperimentalIn 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.
  • MCLA-158

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of patients with Dose Limiting Toxicities (DLTs)
Time Frame:6-12 months
Safety Issue:
Description:Evaluation of number of participants with treatment related toxicities observed during the dose escalation.

Secondary Outcome Measures

Measure:Incidence of anti-drug antibodies against MCLA-158
Time Frame:36 months
Safety Issue:
Description:Number of participants with anti-drug antibodies against MCLA-158
Measure:Serum titers of anti-drug antibodies
Time Frame:36 months
Safety Issue:
Description:Serum titers of anti-drug antibodies against MCLA-158
Measure:Cytokine Panel Expression Profile
Time Frame:36 months
Safety Issue:
Description:Evaluation of the cytokine expression profile
Measure:Biomarkers for EGFR activation and signaling
Time Frame:36 months
Safety Issue:
Description:Evaluation of biomarker results for EGFR activation and signaling
Measure:Biomarkers for resistance to EGFR therapies
Time Frame:36 months
Safety Issue:
Description:Evaluation of biomarker results for resistance to EGFR therapies
Measure:Biomarkers for Wnt signaling in CTCs, proteins, ctDNA, and miRNA
Time Frame:36 months
Safety Issue:
Description:Evaluation of biomarker results for Wnt signaling in CTCs, proteins, ctDNA, and miRNA
Measure:Objective overall response rate (ORR)
Time Frame:36 months
Safety Issue:
Description:Evaluation of clinical benefit assessed by RECIST v1.1 determining objective overall response rate (ORR)
Measure:Duration of response (DOR)
Time Frame:36 months
Safety Issue:
Description:Evaluation of clinical benefit assessed by RECIST v1.1 determining duration of response (DOR)
Measure:Progression Free Survival (PFS) and survival
Time Frame:36 months
Safety Issue:
Description:Evaluation of clinical benefit assessed by RECIST v1.1 determining objective progression free survival (PFS) and/or survival
Measure:End of infusion (EOI) plasma concentration [Ceoi]
Time Frame:36 months
Safety Issue:
Description:End of infusion (EOI) plasma concentration [Ceoi] as measured from all individual plasma concentrations
Measure:Maximum plasma concentration [Cmax]
Time Frame:36 months
Safety Issue:
Description:Maximum plasma concentration as measured from all individual plasma concentrations
Measure:Plasma concentration at 0 hours [C0h]
Time Frame:36 months
Safety Issue:
Description:Plasma concentration at 0 hours [C0h] as measured from all individual plasma concentrations
Measure:Area under the concentration versus time curve from time zero to time t [AUC0-t]
Time Frame:36 months
Safety Issue:
Description:Area under the concentration versus time curve from time zero to time t [AUC0-t]
Measure:Area under the concentration versus time curve [AUC0-∞]
Time Frame:36 months
Safety Issue:
Description:Area under the concentration versus time curve [AUC0-∞]
Measure:Clearance of plasma [CL]
Time Frame:36 months
Safety Issue:
Description:Clearance of plasma [CL]
Measure:Volume of distribution at steady state [Vss]
Time Frame:36 months
Safety Issue:
Description:Volume of distribution at steady state [Vss]
Measure:Time to reach maximum concentration [tmax]
Time Frame:36 months
Safety Issue:
Description:Time to reach maximum concentration [tmax]
Measure:Half-life [t1/2]
Time Frame:36 months
Safety Issue:
Description:Half-life [t1/2]

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merus N.V.

Trial Keywords

  • Bispecific antibody
  • First-in-human
  • MCLA-158
  • Antibodies
  • Bispecific
  • immunologic factors
  • Cytokines
  • EGFR
  • LGR5

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