Clinical trial NCT03381274: Oleclumab (MEDI9447) Epidermal Growth Factor Receptor Mutant (EGFRm) Non-small Cell Lung Cancer (NSCLC) Novel Combination Study
Official title: A Multiarm, Open-label, Multicenter, Phase 1b/2 Study to Evaluate Novel Combination Therapies in Subjects With Previously Treated Advanced EGFRm NSCLC
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: EGFR mutated
CD73
A2AR
Oleclumab
MEDI9447
AZD4635
Osimertinib
NSCLC
Immunotherapy
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2017-12-21
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 101
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to investigate the safety, tolerability, and antitumor activity of novel combination therapies administered in participants with advanced EGFRm NSCLC.


Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18
2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
3. Weight ≥ 35 kg
4. Diagnosed with histologically or cytologically confirmed locally advanced/metastatic NSCLC with EGFRm

   * For Arm A (Oleclumab + Osimertinib arms): must have received 1 prior line of therapy with an EGFR tyrosine kinase inhibitor (TKI) and confirmed T790M negative
   * For Arm B (Oleclumab + AZD4635 arms): must have received at least 2 but not more than 4 prior lines of therapy.

Exclusion Criteria:

1. Receipt of an EGFR TKI within 14 days of the first dose of study treatment
2. Receipt of any conventional or investigational anticancer therapy not otherwise specified within 21 days of the planned first dose
3. Prior receipt of any investigational immunotherapy. Participants may have received agents that have local health authority approval for the disease indication
4. Concurrent enrollment in another therapeutic clinical study. Enrollment in observational studies will be allowed.
5. Participants with a history of venous thrombosis within the past 3 months
6. Participants with prior history of myocardial infarction, transient ischemic attack, or stroke in the last 6 months
7. Active or prior documented autoimmune or inflammatory disorders within the past 3 years prior to the start of treatment
8. Other invasive malignancy within 2 years
9. Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression
10. Current or prior use of immunosuppressive medication within 14 days prior to the first dose

Additional Exclusion Criteria for Arm A

1. Concurrent treatment (or inability to stop therapy) with medications or herbal supplements known to be potent inducers of cytochrome P (CYP) 3A4
2. Participants has a history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD
3. Participants requires continuous supplemental oxygen for any reason

Additional Exclusion Criteria for Arm B

1. Herbal preparations/medications are not allowed throughout the study
2. History of seizures excluding those that occurred due to previously untreated CNS metastasis

Primary outcomes:
measure: Number of Participants With Dose-limiting Toxicities (DLTs) in Part 1
timeFrame: From Day 1 to Day 28 after first dose of study drug
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Parts 1 and 2
timeFrame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
measure: Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2
timeFrame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
measure: Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2
timeFrame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
measure: Number of Participants With Notable QTc Interval in Parts 1 and 2
timeFrame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
measure: Percentage of Participants With Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in Part 2
timeFrame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
Secondary outcomes:
measure: Duration of Response (DoR) Per RECIST v 1.1 for Parts 1 and 2
timeFrame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
measure: Percentage of Participants With Disease Control (DC) in Parts 1 and 2
timeFrame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
measure: Progression Free Survival (PFS) for Parts 1 and 2
timeFrame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
measure: Overall Survival (OS) for Parts 1 and 2
timeFrame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
measure: Percentage of Participants With OR by T790M Status at Baseline (Determined by a Central Laboratory) for Parts 1 and 2
timeFrame: From Baseline (Days -28 to -1) through 90 days of the last dose of study drug (approximately 37 months)
measure: Percentage of Participants With DC by T790M Status at Baseline (Determined by a Central Laboratory) for Parts 1 and 2
timeFrame: From Baseline (Days -28 to -1) through 90 days of the last dose of study drug (approximately 37 months)
measure: Observed Serum Concentration at the Time of End of Infusion (CEOI) of Oleclumab (MEDI9447) Over Time
timeFrame: Predose (within 90 minutes prior to start of infusion) and postdose (10 minutes after the end of infusion) on Days 1 and 57
measure: Observed Lowest Serum Concentration (Ctrough) of MEDI9447 Over Time
timeFrame: Predose (within 90 minutes prior to start of infusion) on Day 57
measure: Maximum Plasma Concentration (Cmax) of Osimertinib and Its Metabolite (AZ5104)
timeFrame: Predose (within 90 minutes prior to start of infusion) and postdose (1, 2, and 4 hours) on Days 1 and 29
measure: Cmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X)
timeFrame: Predose (within 90 minutes prior to start of infusion) and postdose (1, 2, 4, 6, and 24 hours) on Days 1 and 57
measure: Tmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X)
timeFrame: Predose (within 90 minutes prior to start of infusion) and postdose (1, 2, 4, 6, and 24 hours) on Days 1 and 57
measure: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X)
timeFrame: Predose (within 90 minutes prior to start of infusion) and postdose (1, 2, 4, 6, and 24 hours) on Days 1 and 57
measure: Number of Participants With Positive Post-baseline for Anti-oleclumab Antibodies
timeFrame: Predose on Days 1 (Baseline), 29, and 57, and later every 12 weeks through the 12 months and 90 days after the last dose of study drug (approximately 37 months)
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: New York
country: United States
facility: Research Site
state: New York
city: Houston
country: United States
facility: Research Site
state: Texas
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: Taichung
country: Taiwan
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: MedImmune LLC
role: STUDY_DIRECTOR
References: