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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02671435
Recruitment Status : Active, not recruiting
First Posted : February 2, 2016
Last Update Posted : October 7, 2021
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Study Description
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Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Combination Product: Intervention Phase 1 Phase 2

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 383 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of Durvalumab and Monalizumab in Adult Subjects With Select Advanced Solid Tumors
Actual Study Start Date : February 22, 2016
Estimated Primary Completion Date : October 29, 2021
Estimated Study Completion Date : October 29, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Part 1 -Dose escalation with 5 dose escalation cohorts
Durvalumab and monalizumab
 Combination Product: Intervention
Biological: Durvalumab Biological: Monalizumab Biological: Cetuximab
Experimental: Part 2 - Dose expansion with 4 dose expansion cohorts
Durvalumab with monalizumab
 Combination Product: Intervention
Biological: Durvalumab Biological: Monalizumab Biological: Cetuximab
Experimental: Part 3 -Dose Exploration with 10 dose exploration cohorts.
Durvalumab 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.
 Combination Product: Intervention
Biological: Durvalumab Biological: Monalizumab Biological: Cetuximab


Outcome Measures
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Primary Outcome Measures :
  1. Occurrence of Drug Limited Toxicities (DLTs) [ Time Frame: From Time of First dose through DLT Screening period ]
    To assess by the occurrence of Drug Limited Toxicities (DLTs)

  2. Number of patients with changes in vital signs from baseline [ Time Frame: From time of screening through 90 days (+/- 7 days) after the last dose of study medication ]
    To assess safety of monalizumab +durva, or monalizumab+durva +standard of care systemic therapy with or without biological agent or monalizumab + with biological agent

  3. Occurrence of adverse events (AEs) [ Time Frame: From time of screening through 90 days (+/- 7 days) after the last dose of study medication ]
    To assess by the occurrence of adverse events (AEs)

  4. Number of patients with changes in electrocariogram (ECG) from baseline [ Time Frame: From time of screening through 90 days (+/- 7 days) after the last dose of study medication ]
    To assess safety of monalizumab +durva, or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent

  5. Occurrence of serious adverse events (SAEs) [ Time Frame: From time of screening through 90 days (+/- 7 days) after the last dose of study medication ]
    To assess by the occurrence of serious adverse events (SAEs)

  6. Number of patients with changes in laboratory parameters from baseline [ Time Frame: From time of screening through 90 days (+/- 7 days) after the last dose of study medication ]
    To assess safety of monalizumab +durva, or monalizumab +durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent

  7. Objective Response Rate (ORR) [ Time Frame: From time of first dose of study medication through 5 years ]
    To assess anti-tumor activity of monalizumab + durva without biological agent, or monalizumab + with biological agent


Secondary Outcome Measures :
  1. 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 ]
    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

  2. 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 ]
    To assess the immunogenicity of mona+durva with or without standard of care systemic therapy or biological agent, or monalizumab + with biological agent

  3. 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 ]
    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

  4. 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 ]
    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

  5. 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 ]
    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

  6. 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 ]
    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

  7. Objective Response Rate (ORR) [ Time Frame: From time of first dose of study medication through 5 years ]
    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

  8. Progression Free Survival (PFS) [ Time Frame: From time of first dose of study medication through 5 years ]
    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

  9. Disease Control Rate (DC) [ Time Frame: From time of first dose of study medication through 5 years ]
    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

  10. Overall Survival (OS) [ Time Frame: From time of first dose of study medication through 5 years ]
    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

  11. Duration of Response (DoR) [ Time Frame: From time of first dose of study medication through 5 years ]
    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


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02671435


Locations
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Sponsors and Collaborators
MedImmune LLC
More Information
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Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT02671435    
Other Study ID Numbers: D419NC00001
D419NC00001 ( Other Grant/Funding Number: Medimmune LLC )
First Posted: February 2, 2016    Key Record Dates
Last Update Posted: October 7, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Keywords provided by MedImmune LLC:
Colorectal, colon, CRC, solid tumors, check point inhibitors, immunotherapy, metastatic
Additional relevant MeSH terms:
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Neoplasms