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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02671435
Ethics application status
Date submitted
28/01/2016
Date registered
2/02/2016

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
Treatment: Drugs - Monalizumab
Treatment: Drugs - Durvalumab
Treatment: Drugs - Cetuximab
Treatment: Drugs - mFOLFOX6
Treatment: Drugs - Bevacizumab

Experimental: Dose-escalation Cohort 1: Monalizumab 22.5 mg Q2W + Durvalumab 1500 mg Q4W - Participants will receive intravenous (IV) infusions of durvalumab 1500 mg every 4 weeks (Q4W) in combination with monalizumab 22.5 mg every 2 weeks (Q2W) up to 3 years until unacceptable toxicity, documentation of confirmed disease progression (PD), or documentation of subject withdrawal for another reason.

Experimental: Dose-escalation Cohort 2: Monalizumab 75 mg Q2W + Durvalumab 1500 mg Q4W - Participants will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 75 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Experimental: Dose-escalation Cohort 3: Monalizumab 225 mg Q2W + Durvalumab 1500 mg Q4W - Participants will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 225 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Experimental: Dose-escalation Cohort 4: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W - Participants will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Experimental: Dose-escalation Cohort 5: Monalizumab 750 mg Q4W + Durvalumab 1500 mg Q4W - Participants will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q4W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Experimental: Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (MSS-CRC) - Participants with microsatellite-stable colorectal cancer (MSS-CRC) will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Experimental: Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (ovarian) - Participants with ovarian cancer will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Experimental: Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) - Participants with endometrial MSS will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Experimental: Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) - Participants with non-small cell lung cancer (NSCLC) will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Experimental: Exploration Cohort A1: Monalizumab 750 mg Q2W+Durvalumab 1500 mg Q4W+mFOLFOX6 Q2W+Bevacizumab Q2W - Participants with first-line (1L) MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus mFOLFOX (oxaliplatin 85 mg/m\^2 IV infusion, folinic acid 400 mg/m\^2 infusion, fluorouracil 400 mg/m\^2 IV bolus, followed by 2400 mg/m\^2 continuous IV infusion over 46 to 48 hours on Day 1) Q2W plus IV infusion of bevacizumab 5 mg/kg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Experimental: Exploration CohortA2: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + mFOLFOX6 Q2W + Cetuximab Q2W - Participants with 1L MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W, plus mFOLFOX6 (oxaliplatin 85 mg/m\^2, folinic acid 400 mg/m\^2, fluorouracil 400 mg/m\^2 IV bolus, followed by 2400 mg/m\^2 continuous IV infusion over 46 to 48 hours on Day 1) Q2W plus IV infusion of cetuximab (loading dose of 400 mg/m\^2 on Day 1, followed by maintenance dose of 250 mg/m\^2 IV infusion every week starting on Day 8, then changed to 500 mg/m\^2 IV infusion Q2W) up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Experimental: Exploration Cohort C1A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W - Participants with recurrent or metastatic third-line (3L) RAS mutant MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m\^2 on Day 1 then 500 mg/m\^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Experimental: Exploration Cohort C1B: Monalizumab 750 mg Q2W + Cetuximab Q2W - Participants with recurrent or metastatic 3L RAS mutant MSS-CRC will receive IV infusion of monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m\^2 on Day 1 then 500 mg/m\^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Experimental: Exploration Cohort C2A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W - Participants with recurrent or metastatic 3L RAS/BRAF wild type MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m\^2 on Day 1 then 500 mg/m\^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.

Experimental: Exploration Cohort C2B: Monalizumab 750 mg Q2W + Cetuximab Q2W - Participants with recurrent or metastatic 3L RAS/BRAF wild type MSS-CRC will receive IV infusion of monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m\^2 on Day 1 then 500 mg/m\^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.


Treatment: Drugs: Monalizumab
Participants will receive IV infusion of monalizumab as stated in arm description.

Treatment: Drugs: Durvalumab
Participants will receive IV infusion of durvalumab as stated in arm description.

Treatment: Drugs: Cetuximab
Participants will receive IV infusion of cetuximab as stated in arm description.

Treatment: Drugs: mFOLFOX6
Participants will receive IV infusion of mFOLFOX as stated in arm description.

Treatment: Drugs: Bevacizumab
Participants will receive IV infusion of bevacizumab as stated in arm description.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Timepoint [1] 0 0
Day 1 through 246.9 weeks (maximum observed duration)
Primary outcome [2] 0 0
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Timepoint [2] 0 0
Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Primary outcome [3] 0 0
Change From Baseline in Respiratory Rate (RR)
Timepoint [3] 0 0
Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Primary outcome [4] 0 0
Change From Baseline in Pulse Rate (PR)
Timepoint [4] 0 0
Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Primary outcome [5] 0 0
Change From Baseline in Body Temperature (BT)
Timepoint [5] 0 0
Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Primary outcome [6] 0 0
Change From Baseline in Oxygen Saturation (OS)
Timepoint [6] 0 0
Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Primary outcome [7] 0 0
Number of Participants With Notable Change in QTcF and QTcB From Baseline
Timepoint [7] 0 0
Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Primary outcome [8] 0 0
Number of Participants With at Least 2-Grade Shift From Baseline in Laboratory Parameters
Timepoint [8] 0 0
Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Primary outcome [9] 0 0
Number of Participants With Dose Limiting Toxicities (DLTs)
Timepoint [9] 0 0
From Day 1 to 28 days after the first dose of study drugs
Primary outcome [10] 0 0
Percentage of Participants With Objective Response (OR) in Exploration Cohorts C1A and C1B
Timepoint [10] 0 0
Baseline (Days -28 to -1) through 54.8 months (maximum observed duration)
Secondary outcome [1] 0 0
Percentage of Participants With OR
Timepoint [1] 0 0
Baseline (Days -28 to -1) through 54.8 months (maximum observed duration)
Secondary outcome [2] 0 0
Percentage of Participants With OR in Exploration Cohorts C2A and C2B
Timepoint [2] 0 0
Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
Secondary outcome [3] 0 0
Percentage of Participants With Disease Control (DC)
Timepoint [3] 0 0
Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
Secondary outcome [4] 0 0
Percentage of Participants With DC in Exploration Cohorts (C1A, C1B, C2A, and C2B)
Timepoint [4] 0 0
Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
Secondary outcome [5] 0 0
Duration of Response (DoR)
Timepoint [5] 0 0
Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
Secondary outcome [6] 0 0
DoR in Exploration Cohorts (C1A, C1B, C2A, and C2B)
Timepoint [6] 0 0
Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
Secondary outcome [7] 0 0
Progression-Free Survival (PFS)
Timepoint [7] 0 0
Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
Secondary outcome [8] 0 0
Progression-Free Survival (PFS) in Exploration Cohorts (C1A, C1B, C2A, and C2B)
Timepoint [8] 0 0
Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
Secondary outcome [9] 0 0
Overall Survival
Timepoint [9] 0 0
Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
Secondary outcome [10] 0 0
Overall Survival in Exploration Cohorts (C1A, C1B, C2A, and C2B)
Timepoint [10] 0 0
Baseline (-28 to -1 day) through 54.8 weeks (maximum observed duration)
Secondary outcome [11] 0 0
Maximum Observed Serum Concentration (Cmax) of Monalizumab
Timepoint [11] 0 0
Day 85: Pre-dose and end of infusion (within 10 minutes) after cohort specific infusions
Secondary outcome [12] 0 0
Minimum Observed Serum Concentration (Cmin) of Monalizumab
Timepoint [12] 0 0
Day 85: Pre-dose and end of infusion (within 10 minutes) after cohort specific infusions
Secondary outcome [13] 0 0
Serum Concentration of Durvalumab
Timepoint [13] 0 0
Pre-dose (PRE) on Day 1 of Weeks 1, 5, 9, 13, and 25 and post-dose (POST) on Day 1 of Weeks 1 and 13
Secondary outcome [14] 0 0
Serum Concentration of Cetuximab
Timepoint [14] 0 0
Pre-dose (PRE) on Day 1 of Weeks 1, 5, 9, and 13 and post-dose (POST) on Day 1 of Weeks 1, 5, and 13
Secondary outcome [15] 0 0
Number of Participants With Positive Anti-Drug Antibodies (ADA) to Monalizumab
Timepoint [15] 0 0
Day 1 through 54.8 months (Day 1 of Weeks 1, 5, 13, and 25, and 90 days after the last dose of monalizumab)
Secondary outcome [16] 0 0
Number of Participants With Positive ADA to Durvalumab
Timepoint [16] 0 0
Day 1 through 54.8 months (Day 1 of Weeks 1, 5, 13, and 25, and 90 days after the last dose of monalizumab)
Secondary outcome [17] 0 0
Number of Participants With Positive ADA to Cetuximab
Timepoint [17] 0 0
Day 1 through 54.8 months (Day 1 of Weeks 1, 5, 9 [if EOT occurred], and 13, and 30 days after the last dose of monalizumab)
Secondary outcome [18] 0 0
Number of Participants With Programmed Death Ligand 1 (PD-L1) Expression in Pretreatment Tumor Biopsies
Timepoint [18] 0 0
Screening (Days -28 to -1)
Secondary outcome [19] 0 0
Number of Participants With Human Leukocyte Antigen (HLA)-E Expression in Pretreatment Tumor Biopsies
Timepoint [19] 0 0
Screening (Days -28 to -1)

Eligibility
Key inclusion criteria
1. Participants must have histologic documentation of advanced recurrent or metastatic cancer.
2. Participants must be at the recurrent/metastatic setting, with selected advanced solid tumors.
3. Participants must have at least one lesion that is measurable by RECIST v1.1
4. Part 3, Dose exploration, CRC participants 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
Sex
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
Randomised controlled 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
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
22/02/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/09/2025
Actual
Sample size
Target
Accrual to date
Final
383
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
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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 document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
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
Available to whom?
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
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02671435