Clinical trial NCT02671435: A Study of Durvalumab (MEDI4736) and Monalizumab in Solid Tumors
Official title: A Phase 1/2 Study of Durvalumab and Monalizumab in Adult Subjects With Select Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumors
Keywords: Colorectal, colon, CRC, solid tumors, check point inhibitors, immunotherapy, metastatic
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2016-02-02
Enrollment: 383
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, open-label, dose-escalation, dose-exploration and dose-expansion study to evaluate the safety, tolerability, antitumor activity, pharmacokinetic (PK), pharmacodynamics, and immunogenicity of durvalumab (MEDI4736) in combination with monalizumab (IPH2201) in adult participants 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 participants 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 participants 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 participants 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 participants with CRC.

Eligibility criteria: 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.

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.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: Day 1 through 246.9 weeks (maximum observed duration)
measure: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
timeFrame: Day 1 (baseline) through 246.9 weeks (maximum observed duration)
measure: Change From Baseline in Respiratory Rate (RR)
timeFrame: Day 1 (baseline) through 246.9 weeks (maximum observed duration)
measure: Change From Baseline in Pulse Rate (PR)
timeFrame: Day 1 (baseline) through 246.9 weeks (maximum observed duration)
measure: Change From Baseline in Body Temperature (BT)
timeFrame: Day 1 (baseline) through 246.9 weeks (maximum observed duration)
measure: Change From Baseline in Oxygen Saturation (OS)
timeFrame: Day 1 (baseline) through 246.9 weeks (maximum observed duration)
measure: Number of Participants With Notable Change in QTcF and QTcB From Baseline
timeFrame: Day 1 (baseline) through 246.9 weeks (maximum observed duration)
measure: Number of Participants With at Least 2-Grade Shift From Baseline in Laboratory Parameters
timeFrame: Day 1 (baseline) through 246.9 weeks (maximum observed duration)
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: From Day 1 to 28 days after the first dose of study drugs
measure: Percentage of Participants With Objective Response (OR) in Exploration Cohorts C1A and C1B
timeFrame: Baseline (Days -28 to -1) through 54.8 months (maximum observed duration)
Secondary outcomes:
measure: Percentage of Participants With OR
timeFrame: Baseline (Days -28 to -1) through 54.8 months (maximum observed duration)
measure: Percentage of Participants With OR in Exploration Cohorts C2A and C2B
timeFrame: Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
measure: Percentage of Participants With Disease Control (DC)
timeFrame: Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
measure: Percentage of Participants With DC in Exploration Cohorts (C1A, C1B, C2A, and C2B)
timeFrame: Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
measure: Duration of Response (DoR)
timeFrame: Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
measure: DoR in Exploration Cohorts (C1A, C1B, C2A, and C2B)
timeFrame: Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
measure: Progression-Free Survival (PFS)
timeFrame: Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
measure: Progression-Free Survival (PFS) in Exploration Cohorts (C1A, C1B, C2A, and C2B)
timeFrame: Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
measure: Overall Survival
timeFrame: Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
measure: Overall Survival in Exploration Cohorts (C1A, C1B, C2A, and C2B)
timeFrame: Baseline (-28 to -1 day) through 54.8 weeks (maximum observed duration)
measure: Maximum Observed Serum Concentration (Cmax) of Monalizumab
timeFrame: Day 85: Pre-dose and end of infusion (within 10 minutes) after cohort specific infusions
measure: Minimum Observed Serum Concentration (Cmin) of Monalizumab
timeFrame: Day 85: Pre-dose and end of infusion (within 10 minutes) after cohort specific infusions
measure: Serum Concentration of Durvalumab
timeFrame: 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
measure: Serum Concentration of Cetuximab
timeFrame: 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
measure: Number of Participants With Positive Anti-Drug Antibodies (ADA) to Monalizumab
timeFrame: Day 1 through 54.8 months (Day 1 of Weeks 1, 5, 13, and 25, and 90 days after the last dose of monalizumab)
measure: Number of Participants With Positive ADA to Durvalumab
timeFrame: Day 1 through 54.8 months (Day 1 of Weeks 1, 5, 13, and 25, and 90 days after the last dose of monalizumab)
measure: Number of Participants With Positive ADA to Cetuximab
timeFrame: 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)
measure: Number of Participants With Programmed Death Ligand 1 (PD-L1) Expression in Pretreatment Tumor Biopsies
timeFrame: Screening (Days -28 to -1)
measure: Number of Participants With Human Leukocyte Antigen (HLA)-E Expression in Pretreatment Tumor Biopsies
timeFrame: Screening (Days -28 to -1)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Scottsdale
country: United States
facility: Research Site
state: Arizona
city: Duarte
country: United States
facility: Research Site
state: California
city: La Jolla
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Sacramento
country: United States
facility: Research Site
state: California
city: Santa Monica
country: United States
facility: Research Site
state: California
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: New Brunswick
country: United States
facility: Research Site
state: New Jersey
city: Bronx
country: United States
facility: Research Site
state: New York
city: New Hyde Park
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Providence
country: United States
facility: Research Site
state: Rhode Island
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Dallas
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Blacktown
country: Australia
facility: Research Site
city: Clayton
country: Australia
facility: Research Site
city: Waratah
country: Australia
facility: Research Site
city: Bruxelles
country: Belgium
facility: Research Site
city: Edegem
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Marseille CEDEX 5
country: France
facility: Research Site
city: Nantes CEDEX 1
country: France
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Grafton
country: New Zealand
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Sutton
country: United Kingdom
facility: Research Site
Study officials:
References: