Oleclumab (MEDI9447) Epidermal Growth Factor Receptor Mutant (EGFRm) Non-small Cell Lung Cancer (NSCLC) Novel Combination Study

NCT03381274 | Active Not Recruiting Phase 1 Results FDA Drug

• 1 other identifier: D6070C00004
• Study Type: interventional
• Target: 43
• Locations: 3 countries
• Sites: 13

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.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

EGFR mutated; CD73; A2AR; Oleclumab; MEDI9447; AZD4635; Osimertinib; NSCLC; Immunotherapy

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Dose-limiting Toxicities (DLTs) in Part 1

  A DLT was defined as \>= Grade 3 toxicity or adverse events (AE) occurred during DLT evaluation period which included any Grade 4 immune-mediated (immune nature) AE, anemia, thrombocytopenia (present \> 4 days), or neutropenia (present \> 4 days); \>= Grade 3 colitis or pneumonitis or interstitial lung disease (ILD); \>= Grade 3 nausea, vomiting, or diarrhea (not resolved to \<= Grade 2 in 3 days); Grade 2 pneumonitis or ILD (not resolved to \<= Grade 1 in 3 days); Grade 3 thrombocytopenia with bleeding, any grade febrile neutropenia; convulsions, seizures, or stroke; protocol defined elevations of isolated liver transaminase, isolated total bilirubin (TBL), or Hy's Law; confirmed QT interval corrected for heart rate by Fridericia's formula prolongation (\>= 501 msec) on triplicate electrocardiograms within a short period of time; or any other toxicity greater than that at baseline, was clinically significant and/or unacceptable, and was judged to be a DLT by the Dose Escalation Committee.

  From Day 1 to Day 28 after first dose of study drug

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Parts 1 and 2

  An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

  From Day 1 through 90 days of the last dose of study drug (approximately 37 months)

• Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2

  Participants with abnormal laboratory parameters reported as TEAEs are reported. Laboratory analysis included hematology, clinical chemistry, thyroid function tests, and urinalysis.

  From Day 1 through 90 days of the last dose of study drug (approximately 37 months)

• Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2

  Participants with abnormal vital signs (heart rate, blood pressure, temperature, and respiratory rate) and physical examination reported as TEAEs are reported.

  From Day 1 through 90 days of the last dose of study drug (approximately 37 months)

• Number of Participants With Notable QTc Interval in Parts 1 and 2

  Notable QTc intervals included single beat changes from baseline (Day 1) values (\> 30, \> 60, and \> 90 milliseconds). Participants who had notable QTc interval are reported.

  From Day 1 through 90 days of the last dose of study drug (approximately 37 months)

• Percentage of Participants With Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in Part 2

  The OR is defined as confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1 guidelines. The CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. The PR is defined as \>= 30% decrease in the sum of the diameters of target lesions compared to baseline, and non-progressive disease and not evaluable or no non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between.

  From Day 1 through 90 days of the last dose of study drug (approximately 37 months)

Secondary Outcomes (13)

• Duration of Response (DoR) Per RECIST v 1.1 for Parts 1 and 2

  From Day 1 through 90 days of the last dose of study drug (approximately 37 months)

• Percentage of Participants With Disease Control (DC) in Parts 1 and 2

  From Day 1 through 90 days of the last dose of study drug (approximately 37 months)

• Progression Free Survival (PFS) for Parts 1 and 2

  From Day 1 through 90 days of the last dose of study drug (approximately 37 months)

• Overall Survival (OS) for Parts 1 and 2

  From Day 1 through 90 days of the last dose of study drug (approximately 37 months)

• Percentage of Participants With OR by T790M Status at Baseline (Determined by a Central Laboratory) for Parts 1 and 2

  From Baseline (Days -28 to -1) through 90 days of the last dose of study drug (approximately 37 months)

Study Arms (5)

Oleclumab Dose 1 + Osimertinib Dose 1

EXPERIMENTAL

In Part 1 (dose-escalation), participants will receive intravenous oleclumab (MEDI9447) Dose 1 every 2 weeks (Q2W) and oral osimertinib Dose 1 once daily (QD).

Biological: Oleclumab; Drug: Osimertinib

Oleclumab Dose 2 + Osimertinib Dose 1

EXPERIMENTAL

In Part 1 (dose-escalation), participants will receive intravenous oleclumab Dose 2 Q2W and oral osimertinib Dose 1 QD. In Part 2 (dose-expansion), participants (including participants dosed at the RP2D in Part 1) will receive IV oleclumab Dose 2 Q2W and oral osimertinib Dose 1 QD until documentation of disease progression, intolerable toxicity, or development of other reason for treatment discontinuation, whichever occurs first.

Biological: Oleclumab; Drug: Osimertinib

Oleclumab Dose 1 + AZD4635 Dose 1

EXPERIMENTAL

In Part 1 (dose-escalation), participants will receive intravenous oleclumab Dose 1 Q2W and oral AZD4635 Dose 1 QD.

Biological: Oleclumab; Drug: AZD4635

Oleclumab Dose 1 + AZD4635 Dose 2

EXPERIMENTAL

In Part 1 (dose-escalation), participants will receive intravenous oleclumab Dose 1 Q2W and oral AZD4635 Dose 2 QD.

Biological: Oleclumab; Drug: AZD4635

Oleclumab Dose 2 + AZD4635 Dose 2

EXPERIMENTAL

In Part 1 (dose-escalation), participants will receive intravenous oleclumab Dose 2 Q2W and oral AZD4635 Dose 2 QD.

Biological: Oleclumab; Drug: AZD4635

Interventions

Oleclumab BIOLOGICAL

Participants will receive oleclumab in combination with osimertinib or AZD4635 as stated in the arms' description.

Also known as: MEDI9447

Oleclumab Dose 1 + AZD4635 Dose 1; Oleclumab Dose 1 + AZD4635 Dose 2; Oleclumab Dose 1 + Osimertinib Dose 1; Oleclumab Dose 2 + AZD4635 Dose 2; Oleclumab Dose 2 + Osimertinib Dose 1

Osimertinib DRUG

Participants will receive osimertinib in combination with oleclumab as stated in the arms' description.

Also known as: Tagrisso®

Oleclumab Dose 1 + Osimertinib Dose 1; Oleclumab Dose 2 + Osimertinib Dose 1

AZD4635 DRUG

Participants will receive AZD4635 in combination with oleclumab as stated in the arms' description.

Oleclumab Dose 1 + AZD4635 Dose 1; Oleclumab Dose 1 + AZD4635 Dose 2; Oleclumab Dose 2 + AZD4635 Dose 2

Eligibility Criteria

• Age: 18 Years - 101 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Weight ≥ 35 kg
• 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.

You may not qualify if:

• Receipt of an EGFR TKI within 14 days of the first dose of study treatment
• Receipt of any conventional or investigational anticancer therapy not otherwise specified within 21 days of the planned first dose
• Prior receipt of any investigational immunotherapy. Participants may have received agents that have local health authority approval for the disease indication
• Concurrent enrollment in another therapeutic clinical study. Enrollment in observational studies will be allowed.
• Participants with a history of venous thrombosis within the past 3 months
• Participants with prior history of myocardial infarction, transient ischemic attack, or stroke in the last 6 months
• Active or prior documented autoimmune or inflammatory disorders within the past 3 years prior to the start of treatment
• Other invasive malignancy within 2 years
• Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression
• Current or prior use of immunosuppressive medication within 14 days prior to the first dose
• Concurrent treatment (or inability to stop therapy) with medications or herbal supplements known to be potent inducers of cytochrome P (CYP) 3A4
• 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
• Participants requires continuous supplemental oxygen for any reason
• Herbal preparations/medications are not allowed throughout the study
• History of seizures excluding those that occurred due to previously untreated CNS metastasis

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (13)

Research Site

La Jolla, California, 92093, United States

Location

Research Site

San Francisco, California, 94143, United States

Location

Research Site

Aurora, Colorado, 80045, United States

Location

Research Site

New Haven, Connecticut, 06510, United States

Location

Research Site

Atlanta, Georgia, 30322, United States

Location

Research Site

Chicago, Illinois, 60611, United States

Location

Research Site

Baltimore, Maryland, 21224, United States

Location

Research Site

New York, New York, 10032, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Research Site

Seoul, 03080, South Korea

Location

Research Site

Seoul, 05505, South Korea

Location

Research Site

Seoul, 06351, South Korea

Location

Research Site

Taichung, 40705, Taiwan

Location

Related Publications (1)

• Kim DW, Kim SW, Camidge DR, Shu CA, Marrone KA, Le X, Blakely CM, Park K, Chang GC, Patel SP, Kar G, Cooper ZA, Samadani R, Pluta M, Kumar R, Ramalingam S. CD73 Inhibitor Oleclumab Plus Osimertinib in Previously Treated Patients With Advanced T790M-Negative EGFR-Mutated NSCLC: A Brief Report. J Thorac Oncol. 2023 May;18(5):650-656. doi: 10.1016/j.jtho.2022.12.021. Epub 2023 Jan 11.

  PMID: 36641093 DERIVED

Related Links

• D6070C00004 redacted protocol
• D6070C00004 SAP redacted
• D6070C00004 CSR Synopsis redacted

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

Arm B (Oleclumab + AZD4635 groups) did not proceed to the dose expansion phase due to lack of response to treatment and a change in the formulation of AZD4635. The OR and DC by T790M status for 'Oleclumab + AZD4635' groups were not conducted due to the small sample size.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca Clinical Study Information Center

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• MedImmune LLC

  MedImmune LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2017
• First Posted: December 21, 2017
• Study Start: May 8, 2018
• Primary Completion: May 24, 2021
• Study Completion: April 16, 2026
• Last Updated: March 11, 2026
• Results First Posted: July 26, 2022

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 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.
• Access Criteria: 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.

Locations

KR (3); TW (1); US (9)