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

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)
Estimated Enrollment :	501 participants
Allocation:	Non-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 15, 2021
Estimated Study Completion Date :	October 15, 2021

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 PD-L1 and HLA-E. [ 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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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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Contacts

Contact: AstraZeneca Clinical Study Information Center	1-877-240-9479	information.center@astrazeneca.com

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Sponsors and Collaborators

MedImmune LLC

More Information

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Responsible Party:	MedImmune LLC
ClinicalTrials.gov Identifier:	NCT02671435 History of Changes
Other Study ID Numbers:	D419NC00001; D419NC00001 ( Other Grant/Funding Number: Medimmune LLC )
First Posted:	February 2, 2016
Last Update Posted:	January 8, 2019
Last Verified:	January 2019

Keywords provided by MedImmune LLC:

Colorectal cancer, colon cancer, CRC, solid tumors, check point inhibitors, immunotherapy, chemotherapy, metastatic

Additional relevant MeSH terms:

Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs