Clinical Trials /

A Study of Durvalumab (MEDI4736) and Monalizumab in Solid Tumors

NCT02671435

Description:

This is a multicenter, open-label, dose-escalation, dose-exploration and dose-expansion study to evaluate the safety, tolerability, antitumor activity, PK, pharmacodynamics, and immunogenicity of Durvalumab (MEDI4736) in combination with monalizumab (IPH2201) in Adult Subjects with selected advanced solid tumors and the combination of durvalumab and monalizumab (IPH2201) standard of care systemic therapy with or without biological agent and monalizumab (IPH2201) with biological agent administered to subjects with recurrent or metastatic colorectal cancer (CRC).

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

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Durvalumab (MEDI4736) and Monalizumab in Solid Tumors
  • Official Title: A Phase 1/2 Study of Durvalumab and Monalizumab in Adult Subjects With Select Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: D419NC00001
  • SECONDARY ID: D419NC00001
  • NCT ID: NCT02671435

Conditions

  • Advanced Solid Tumors

Purpose

This is a multicenter, open-label, dose-escalation, dose-exploration and dose-expansion study to evaluate the safety, tolerability, antitumor activity, PK, pharmacodynamics, and immunogenicity of Durvalumab (MEDI4736) in combination with monalizumab (IPH2201) in Adult Subjects with selected advanced solid tumors and the combination of durvalumab and monalizumab (IPH2201) standard of care systemic therapy with or without biological agent and monalizumab (IPH2201) with biological agent administered to subjects with recurrent or metastatic colorectal cancer (CRC).

Detailed Description

      The study consists of 3 parts: dose escalation (Part 1), dose expansion (Part 2), and dose
      exploration (Part 3). Part 1 will evaluate dose escalation of durvalumab in combination with
      monalizumab in adult subjects with select advanced solid tumor malignancies. Part 2 will
      evaluate further the identified dose of durvalumab in combination with monalizumab from Part
      1 in adult subjects with select advanced solid tumor malignancies. Part 3 will evaluate dose
      exploration of durvalumab in combination with monalizumab and standard of care systemic
      therapy with or without biological agent, and monalizumab in combination with biological
      agent in adult subjects with CRC.
    

Trial Arms

NameTypeDescriptionInterventions
Part 1 -Dose escalation with 5 dose escalation cohortsExperimentalDurvalumab and monalizumab
    Part 2 - Dose expansion with 4 dose expansion cohortsExperimentalDurvalumab with monalizumab
      Part 3 -Dose Exploration with 10 dose exploration cohorts.ExperimentalDurvalumab and monalizumab and standard of standard of care systemic therapy with or without a biologic agent and monalizumab in combination with biologic agent in CRC.

        Eligibility Criteria

                Inclusion Criteria:
        
                  1. Subjects must have histologic documentation of advanced recurrent or metastatic
                     cancer.
        
                  2. Subjects must be at the recurrent/metastatic setting, with selected advanced solid
                     tumors.
        
                  3. Subjects must have at least one lesion that is measurable by RECIST v1.1
        
                  4. Part 3, Dose exploration, CRC subjects can be treatment naïve but should not have
                     received more than two line of systemic therapy in the recurrent/metastatic setting.
        
                Exclusion Criteria
        
                  1. Prior treatment with immunotherapy agents. Prior treatment with antitumor vaccines may
                     be permitted upon discussion with the medical monitor.
        
                  2. Prior participation in clinical studies that include durvalumab alone or in
                     combination, where the study has registrational intent and the analyses for the
                     primary endpoint have not yet been completed
        
                  3. Receipt of any conventional or investigational anticancer therapy within 4 weeks prior
                     to the first dose of study treatment
        
                  4. Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer
                     treatment. Concurrent use of hormones for non-cancer-related conditions is acceptable.
              
        Maximum Eligible Age:99 Years
        Minimum Eligible Age:18 Years
        Eligible Gender:All
        Healthy Volunteers:No

        Primary Outcome Measures

        Measure:Occurrence of Drug Limited Toxicities (DLTs)
        Time Frame:From Time of First dose through DLT Screening period
        Safety Issue:
        Description:To assess by the occurrence of Drug Limited Toxicities (DLTs)

        Secondary Outcome Measures

        Measure:Expression of pre-treatment protein within the tumor microenvironment
        Time Frame:From time of screening through 90 days (+/- 7 days) after the last dose of study medication
        Safety Issue:
        Description:To assess biomarker predicting activity of monalizumab+durva in combo with standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent
        Measure:Number of subjects who develop anti-drug antibodies
        Time Frame:From time of first dose through 90 days (+/- 7 days) after the last dose of study medication
        Safety Issue:
        Description:To assess the immunogenicity of mona+durva with or without standard of care systemic therapy or biological agent, or monalizumab + with biological agent
        Measure:Durva, monalizumab, biologic agent serum peak concentration (cMax) concentration for Pharmacokinetics
        Time Frame:From time of first dose through 90 days (+/- 7 days) after the last dose of study medication
        Safety Issue:
        Description:To assess the pharmacokinetics of Durvalumab and monalizumab or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent
        Measure:Durva and monalizumab serum area under the concentration-time curve (AUC) concentration for Pharmacokinetics
        Time Frame:From time of first dose through 90 days (+/- 7 days) after the last dose of study medication
        Safety Issue:
        Description:To assess the pharmacokinetics of Durvalumab and monalizumab or monalizumab+durva +standard of care systemic therapy with or without biological agent, monalizumab + with biological agent
        Measure:Durva and monalizumab serum clearance (CL) concentration for Pharmacokinetics
        Time Frame:From time of first dose through 90 days (+/- 7 days) after the last dose of study medication
        Safety Issue:
        Description:To assess the pharmacokinetics of Durvalumab and monalizumab or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent
        Measure:Durva and monalizumab serum terminal elimination half-life (t1/2) concentration for Pharmacokinetics
        Time Frame:From first dose through 90 days (+/- 7 days) after the last dose of study medication
        Safety Issue:
        Description:To assess the pharmacokinetics of Durvalumab and monalizumab or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent
        Measure:Objective Response Rate (ORR)
        Time Frame:From time of first dose of study medication through 5 years
        Safety Issue:
        Description:To assess anti-tumor activity of monalizumab +durva, or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent
        Measure:Progression Free Survival (PFS)
        Time Frame:From time of first dose of study medication through 5 years
        Safety Issue:
        Description:To assess anti-tumor activity of monalizumab +durva, or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent
        Measure:Disease Control Rate (DC)
        Time Frame:From time of first dose of study medication through 5 years
        Safety Issue:
        Description:To assess anti-tumor activity of monalizumab +durva, or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent
        Measure:Overall Survival (OS)
        Time Frame:From time of first dose of study medication through 5 years
        Safety Issue:
        Description:To assess anti-tumor activity of monalizumab +durva, or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent
        Measure:Duration of Response (DoR)
        Time Frame:From time of first dose of study medication through 5 years
        Safety Issue:
        Description:To assess anti-tumor activity of monalizumab +durva, or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent

        Details

        Phase:Phase 1/Phase 2
        Primary Purpose:Interventional
        Overall Status:Recruiting
        Lead Sponsor:MedImmune LLC

        Trial Keywords

        • Colorectal, colon, CRC, solid tumors, check point inhibitors, immunotherapy, metastatic

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