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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02671435




Registration number
NCT02671435
Ethics application status
Date submitted
28/01/2016
Date registered
2/02/2016
Date last updated
20/04/2020

Titles & IDs
Public title
A Study of Durvalumab (MEDI4736) and Monalizumab in Solid Tumors
Scientific title
A Phase 1/2 Study of Durvalumab and Monalizumab in Adult Subjects With Select Advanced Solid Tumors
Secondary ID [1] 0 0
D419NC00001
Secondary ID [2] 0 0
D419NC00001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Combination Product - Intervention

Experimental: Part 1 -Dose escalation with 5 dose escalation cohorts - Durvalumab and monalizumab

Experimental: Part 2 - Dose expansion with 4 dose expansion cohorts - Durvalumab with monalizumab

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

Intervention code [1] 0 0
Combination Product
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Occurrence of Drug Limited Toxicities (DLTs) - To assess by the occurrence of Drug Limited Toxicities (DLTs)
Timepoint [1] 0 0
From Time of First dose through DLT Screening period
Primary outcome [2] 0 0
Number of patients with changes in vital signs from baseline - To assess safety of monalizumab +durva, or monalizumab+durva +standard of care systemic therapy with or without biological agent or monalizumab + with biological agent
Timepoint [2] 0 0
From time of screening through 90 days (+/- 7 days) after the last dose of study medication
Primary outcome [3] 0 0
Occurrence of adverse events (AEs) - To assess by the occurrence of adverse events (AEs)
Timepoint [3] 0 0
From time of screening through 90 days (+/- 7 days) after the last dose of study medication
Primary outcome [4] 0 0
Number of patients with changes in electrocariogram (ECG) from baseline - To assess safety of monalizumab +durva, or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent
Timepoint [4] 0 0
From time of screening through 90 days (+/- 7 days) after the last dose of study medication
Primary outcome [5] 0 0
Occurrence of serious adverse events (SAEs) - To assess by the occurrence of serious adverse events (SAEs)
Timepoint [5] 0 0
From time of screening through 90 days (+/- 7 days) after the last dose of study medication
Primary outcome [6] 0 0
Number of patients with changes in laboratory parameters from baseline - To assess safety of monalizumab +durva, or monalizumab +durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent
Timepoint [6] 0 0
From time of screening through 90 days (+/- 7 days) after the last dose of study medication
Primary outcome [7] 0 0
Objective Response Rate (ORR) - To assess anti-tumor activity of monalizumab + durva without biological agent, or monalizumab + with biological agent
Timepoint [7] 0 0
From time of first dose of study medication through 5 years
Secondary outcome [1] 0 0
Expression of pre-treatment protein within the tumor microenvironment - 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
Timepoint [1] 0 0
From time of screening through 90 days (+/- 7 days) after the last dose of study medication
Secondary outcome [2] 0 0
Number of subjects who develop anti-drug antibodies - To assess the immunogenicity of mona+durva with or without standard of care systemic therapy or biological agent, or monalizumab + with biological agent
Timepoint [2] 0 0
From time of first dose through 90 days (+/- 7 days) after the last dose of study medication
Secondary outcome [3] 0 0
Durva, monalizumab, biologic agent serum peak concentration (cMax) concentration for Pharmacokinetics - 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
Timepoint [3] 0 0
From time of first dose through 90 days (+/- 7 days) after the last dose of study medication
Secondary outcome [4] 0 0
Durva and monalizumab serum area under the concentration-time curve (AUC) concentration for Pharmacokinetics - 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
Timepoint [4] 0 0
From time of first dose through 90 days (+/- 7 days) after the last dose of study medication
Secondary outcome [5] 0 0
Durva and monalizumab serum clearance (CL) concentration for Pharmacokinetics - 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
Timepoint [5] 0 0
From time of first dose through 90 days (+/- 7 days) after the last dose of study medication
Secondary outcome [6] 0 0
Durva and monalizumab serum terminal elimination half-life (t1/2) concentration for Pharmacokinetics - 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
Timepoint [6] 0 0
From first dose through 90 days (+/- 7 days) after the last dose of study medication
Secondary outcome [7] 0 0
Objective Response Rate (ORR) - 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
Timepoint [7] 0 0
From time of first dose of study medication through 5 years
Secondary outcome [8] 0 0
Progression Free Survival (PFS) - 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
Timepoint [8] 0 0
From time of first dose of study medication through 5 years
Secondary outcome [9] 0 0
Disease Control Rate (DC) - 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
Timepoint [9] 0 0
From time of first dose of study medication through 5 years
Secondary outcome [10] 0 0
Overall Survival (OS) - 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
Timepoint [10] 0 0
From time of first dose of study medication through 5 years
Secondary outcome [11] 0 0
Duration of Response (DoR) - 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
Timepoint [11] 0 0
From time of first dose of study medication through 5 years

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
99 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Blacktown
Recruitment hospital [2] 0 0
Research Site - Clayton
Recruitment hospital [3] 0 0
Research Site - Waratah
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
2298 - Waratah
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
New Jersey
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
Rhode Island
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Utah
Country [16] 0 0
Belgium
State/province [16] 0 0
Bruxelles
Country [17] 0 0
Belgium
State/province [17] 0 0
Edegem
Country [18] 0 0
Belgium
State/province [18] 0 0
Leuven
Country [19] 0 0
Canada
State/province [19] 0 0
British Columbia
Country [20] 0 0
Canada
State/province [20] 0 0
Ontario
Country [21] 0 0
France
State/province [21] 0 0
Marseille CEDEX 5
Country [22] 0 0
France
State/province [22] 0 0
Nantes CEDEX 1
Country [23] 0 0
Hungary
State/province [23] 0 0
Debrecen
Country [24] 0 0
Italy
State/province [24] 0 0
Milano
Country [25] 0 0
Korea, Republic of
State/province [25] 0 0
Seoul
Country [26] 0 0
New Zealand
State/province [26] 0 0
Grafton
Country [27] 0 0
Spain
State/province [27] 0 0
Barcelona
Country [28] 0 0
Spain
State/province [28] 0 0
Madrid
Country [29] 0 0
Spain
State/province [29] 0 0
Málaga
Country [30] 0 0
Spain
State/province [30] 0 0
Pamplona
Country [31] 0 0
Spain
State/province [31] 0 0
Sevilla
Country [32] 0 0
United Kingdom
State/province [32] 0 0
London
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
MedImmune LLC
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/show/NCT02671435
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications