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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02671435
Recruitment Status : Recruiting
First Posted : February 2, 2016
Last Update Posted : January 18, 2020
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Tracking Information
First Submitted Date  ICMJE January 28, 2016
First Posted Date  ICMJE February 2, 2016
Last Update Posted Date January 18, 2020
Actual Study Start Date  ICMJE February 22, 2016
Estimated Primary Completion Date March 18, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 8, 2018)
  • 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)
  • 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
  • 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)
  • 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
  • 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)
  • 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
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: January 28, 2016)
  • Number of subjects reporting adverse events [ Time Frame: Screening through 90 days after the last dose of study medication ]
  • Number of subjects reporting serious adverse events [ Time Frame: Screening through 90 days after the last dose of study medication ]
  • Number of subjects experiencing dose-limiting toxicities [ Time Frame: First dose of study medications through 4 weeks after the first dose of study medication ]
  • Change from Baseline in laboratory evaluations [ Time Frame: Screening through 90 days after the last dose of study medication ] ]
  • Change from Baseline in electrocardiograms [ Time Frame: Screening through 90 days through last dose of study medication ]
  • Change from Baseline in vital signs [ Time Frame: Screening through 90 days after the last dose of study medication ]
Change History Complete list of historical versions of study NCT02671435 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2019)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: January 28, 2016)
  • Objective Response Rate [ Time Frame: Time Frame: Screening through 5 years after the last subject receives the first dose of study medication ]
  • Disease Control Rate [ Time Frame: Screening through 5 years after the last subject receives the first dose of study medication ]
  • Duration of Response [ Time Frame: Screening through 5 years after the last subject receives the first dose of study medication ]
  • Individual Durvalumab concentrations [ Time Frame: First dose of Durvalumab through 3 months after the last dose of study medication ]
  • Individual IPH2201 Concentration [ Time Frame: First dose of IPH2201 through 3 months after the last dose of study medication ]
  • Durvalumab area under the concentration-curve [ Time Frame: First dose of Durvalumab through 3 months after the last dose of study medication ]
  • IPH2201 area under the concentration-curve [ Time Frame: First dose of IPH2201 through 3 months after the last dose of study medication ]
  • Number of subjects and percentage of subjects who develop detectable anti-drug antibodies [ Time Frame: First dose of Durvalumab through 3 months after the last dose of study medication ]
  • Progression Free Survival [ Time Frame: Screening through 5 years after the last subject receives the first dose of study medication ]
  • Overall Survival [ Time Frame: Screening through 5 years after the last subject receives the first dose of study medication ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Durvalumab (MEDI4736) and Monalizumab in Solid Tumors
Official Title  ICMJE A Phase 1/2 Study of Durvalumab and Monalizumab in Adult Subjects With Select Advanced Solid Tumors
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).
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors
Intervention  ICMJE Combination Product: Intervention
Biological: Durvalumab Biological: Monalizumab Biological: Cetuximab
Study Arms  ICMJE
  • Experimental: Part 1 -Dose escalation with 5 dose escalation cohorts
    Durvalumab and monalizumab
    Intervention: Combination Product: Intervention
  • Experimental: Part 2 - Dose expansion with 4 dose expansion cohorts
    Durvalumab with monalizumab
    Intervention: Combination Product: Intervention
  • 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.
    Intervention: Combination Product: Intervention
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 14, 2020)
381
Original Estimated Enrollment  ICMJE
 (submitted: January 28, 2016)
208
Estimated Study Completion Date  ICMJE March 18, 2022
Estimated Primary Completion Date March 18, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Listed Location Countries  ICMJE Australia,   Belgium,   Brazil,   Canada,   France,   Hungary,   Italy,   Korea, Republic of,   New Zealand,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02671435
Other Study ID Numbers  ICMJE D419NC00001
D419NC00001 ( Other Grant/Funding Number: Medimmune LLC )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party MedImmune LLC
Study Sponsor  ICMJE MedImmune LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account MedImmune LLC
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP