Carcinoma, Non-Small-Cell LungPhase 1/2NCT03381274

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

A Phase 1/2 study testing Oleclumab, Osimertinib and AZD4635 in people with Carcinoma, Non-Small-Cell Lung, run by MedImmune LLC at 13 sites in 3 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 101 years
Conditions the study is for: Carcinoma, Non-Small-Cell Lung
What is being tested?: Oleclumab, Osimertinib and AZD4635
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 43 participants
Where: 13 sitesin 3 countries
Study dates: 8 May 2018to 6 Nov 2026
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 101 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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

Show all 17Show fewer

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
Additional Exclusion Criteria for Arm A
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
Additional Exclusion Criteria for Arm B
Herbal preparations/medications are not allowed throughout the study
History of seizures excluding those that occurred due to previously untreated CNS metastasis

Trial locations and contacts

13 sites in 3 countries.

Country

City, postcode or hospital

13 sites in 3 countries

United States9 sites

Research Site
Atlanta, Georgia, 30322
Research Site
Aurora, Colorado, 80045
Research Site
Baltimore, Maryland, 21224
Research Site
Chicago, Illinois, 60611
Research Site
Houston, Texas, 77030
Research Site
La Jolla, California, 92093
Research Site
New Haven, Connecticut, 06510
Research Site
New York, New York, 10032
Research Site
San Francisco, California, 94143

Other trials in United States

South Korea3 sites

Research Site
Seoul, 03080
Research Site
Seoul, 05505
Research Site
Seoul, 06351

Other trials in South Korea

Taiwan1 site

Research Site
Taichung, 40705

Other trials in Taiwan

About this 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

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
Being tested: Oleclumab, Osimertinib, AZD4635
Keywords: EGFR mutated, CD73, A2AR, Oleclumab, MEDI9447, AZD4635, Osimertinib, NSCLC, Immunotherapy
Medical subject headings: Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

OleclumabBiological
Also called MEDI9447
Participants will receive oleclumab in combination with osimertinib or AZD4635 as stated in the arms' description.
OsimertinibDrug
Also called Tagrisso®
Participants will receive osimertinib in combination with oleclumab as stated in the arms' description.
AZD4635Drug
Participants will receive AZD4635 in combination with oleclumab as stated in the arms' description.

Study groups in NCT03381274
Study group	Role	What they receive
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). Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Biological: Oleclumab; Drug: AZD4635

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
The DoR is defined as duration from the first documentation of OR (confirmed CR or PR) to the first documented disease progression based on RECIST v1.1 guidelines or death due to any cause, whichever occurs first. A CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. A 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. The progressive disease is defined at least a 20% increase in sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. The DoR was analyzed using Kaplan-Meier method.
Measured: 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
The DC is defined as percentage of participants with CR, PR, or stable disease (SD, which was maintained by >= 8 week) based on RECIST v1.1 guidelines. A CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. A 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. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum longest diameter since the study treatment started, and non-progressive disease and not evaluable or no non-target lesion.
Measured: 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
The PFS is defined as the time from the start of study treatment until the documentation of disease progression based on RECIST version 1.1 or death due to any cause, whichever occurs first, regardless of whether the participant received subsequent anticancer treatment prior to progression. The progressive disease is defined at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. Participants who were alive and progression-free at the time of data cut-off for analysis had PFS censored at the last tumor assessment date. The PFS was estimated using Kaplan-Meier method.
Measured: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
Overall Survival (OS) for Parts 1 and 2
The OS is defined as the time from the start of study treatment until death due to any cause. Participants who are alive at the time of data cut-off had OS censored at the last known to be alive date. The OS was estimated using Kaplan-Meier method.
Measured: 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
The T790M status was determined by plasma testing in a central laboratory at Baseline (Days -28 to -1). The OR is defined as confirmed CR or confirmed 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. Cell-free circulating tumor deoxyribonucleic acid (ctDNA) from liquid biopsy was used as a surrogate marker for T790M status in tumor tissue.
Measured: From Baseline (Days -28 to -1) through 90 days of the last dose of study drug (approximately 37 months)
Percentage of Participants With DC by T790M Status at Baseline (Determined by a Central Laboratory) for Parts 1 and 2
The T790M status was determined by plasma testing in a central laboratory at Baseline (Days -28 to -1). The DC is defined as percentage of participants with CR, PR, or SD (maintained by >= 8 week) based on RECIST v1.1 guidelines. A CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. A PR is defined as >= 30% decrease in the sum of longest diameters of target lesions compared to baseline, and non-progressive disease and not evaluable or no non-target lesion. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum longest diameter since the study treatment started, and persistence of one or more non-target lesion(s). Cell-free circulating tumor deoxyribonucleic acid (ctDNA) from liquid biopsy was used as a surrogate marker for T790M status in tumor tissue.
Measured: From Baseline (Days -28 to -1) through 90 days of the last dose of study drug (approximately 37 months)
Observed Serum Concentration at the Time of End of Infusion (CEOI) of Oleclumab (MEDI9447) Over Time
The CEOI of oleclumab is reported.
Measured: Predose (within 90 minutes prior to start of infusion) and postdose (10 minutes after the end of infusion) on Days 1 and 57
Observed Lowest Serum Concentration (Ctrough) of MEDI9447 Over Time
The Ctrough of oleclumab is reported.
Measured: Predose (within 90 minutes prior to start of infusion) on Day 57
Maximum Plasma Concentration (Cmax) of Osimertinib and Its Metabolite (AZ5104)
The Cmax of osimertinib and AZ5104 are reported.
Measured: Predose (within 90 minutes prior to start of infusion) and postdose (1, 2, and 4 hours) on Days 1 and 29
Cmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X)
The Cmax of AZD4635, SSP-005173X, and SSP-005174X are reported.
Measured: Predose (within 90 minutes prior to start of infusion) and postdose (1, 2, 4, 6, and 24 hours) on Days 1 and 57
Tmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X)
The Tmax of AZD4635, SSP-005173X, and SSP-005174X are reported.
Measured: Predose (within 90 minutes prior to start of infusion) and postdose (1, 2, 4, 6, and 24 hours) on Days 1 and 57
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)
The AUC0-24 of AZD4635, SSP-005173X, and SSP-005174X are reported.
Measured: Predose (within 90 minutes prior to start of infusion) and postdose (1, 2, 4, 6, and 24 hours) on Days 1 and 57
Number of Participants With Positive Post-baseline for Anti-oleclumab Antibodies
Number of participants with positive post-baseline for anti-oleclumab antibodies are reported.
Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

8 May 20186 Nov 2026

First posted21 Dec 2017
Study start8 May 2018
Primary completion24 May 2021
Study completion6 Nov 2026 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 43 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03381274
Sponsor's protocol ID: D6070C00004
Status last verified: Sep 2026
First submitted: 18 Dec 2017
Last updated: 23 Sep 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: 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.

Publications

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.
PubMed 36641093

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 23 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multiarm, Open-label, Multicenter, Phase 1b/2 Study to Evaluate Novel Combination Therapies in Subjects With Previously Treated Advanced EGFRm NSCLC
ClinicalTrials.gov ID: NCT03381274
Acronym / sponsor ID: D6070C00004
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: EGFR mutated, CD73, A2AR, Oleclumab, MEDI9447, AZD4635, Osimertinib, NSCLC
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 43 participants (actual)
Lead sponsor: MedImmune LLCIndustry (pharma, biotech, devices)
Study start: 8 May 2018 (actual)
Primary completion: 24 May 2021 (actual)
Study completion: 6 Nov 2026 (estimated)
First posted: 21 Dec 2017 (actual)
Results: Posted 26 Jul 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
Oleclumab Dose 1 + Osimertinib Dose 1	Experimental	Biological: Oleclumab, Drug: OsimertinibIn Part 1 (dose-escalation), participants will receive intravenous oleclumab (MEDI9447) Dose 1 every 2 weeks (Q2W) and oral osimertinib Dose 1 once daily (QD).
Oleclumab Dose 2 + Osimertinib Dose 1	Experimental	Biological: Oleclumab, Drug: OsimertinibIn 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.
Oleclumab Dose 1 + AZD4635 Dose 1	Experimental	Biological: Oleclumab, Drug: AZD4635In Part 1 (dose-escalation), participants will receive intravenous oleclumab Dose 1 Q2W and oral AZD4635 Dose 1 QD.
Oleclumab Dose 1 + AZD4635 Dose 2	Experimental	Biological: Oleclumab, Drug: AZD4635In Part 1 (dose-escalation), participants will receive intravenous oleclumab Dose 1 Q2W and oral AZD4635 Dose 2 QD.
Oleclumab Dose 2 + AZD4635 Dose 2	Experimental	Biological: Oleclumab, Drug: AZD4635In Part 1 (dose-escalation), participants will receive intravenous oleclumab Dose 2 Q2W and oral AZD4635 Dose 2 QD.

Who may qualify

Ages: 18 to 101 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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

Key exclusion criteria (17 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
OleclumabAlso: MEDI9447Participants will receive oleclumab in combination with osimertinib or AZD4635 as stated in the arms' description.	Biological	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
OsimertinibAlso: Tagrisso®Participants will receive osimertinib in combination with oleclumab as stated in the arms' description.	Drug	Oleclumab Dose 1 + Osimertinib Dose 1, Oleclumab Dose 2 + Osimertinib Dose 1
AZD4635Participants will receive AZD4635 in combination with oleclumab as stated in the arms' description.	Drug	Oleclumab Dose 1 + AZD4635 Dose 1, Oleclumab Dose 1 + AZD4635 Dose 2, Oleclumab Dose 2 + AZD4635 Dose 2

Primary outcome

Number of Participants With Dose-limiting Toxicities (DLTs) in Part 1
Time frame: From Day 1 to Day 28 after first dose of study drug
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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Parts 1 and 2
Time frame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
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.
Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2
Time frame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
Participants with abnormal laboratory parameters reported as TEAEs are reported. Laboratory analysis included hematology, clinical chemistry, thyroid function tests, and urinalysis.
Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs in Parts 1 and 2
Time frame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
Participants with abnormal vital signs (heart rate, blood pressure, temperature, and respiratory rate) and physical examination reported as TEAEs are reported.
Number of Participants With Notable QTc Interval in Parts 1 and 2
Time frame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
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.
Percentage of Participants With Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in Part 2
Time frame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
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.

13 secondary outcomes

Duration of Response (DoR) Per RECIST v 1.1 for Parts 1 and 2
Time frame: 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
Time frame: 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
Time frame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months)
Overall Survival (OS) for Parts 1 and 2
Time frame: 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
Time frame: From Baseline (Days -28 to -1) through 90 days of the last dose of study drug (approximately 37 months)
Percentage of Participants With DC by T790M Status at Baseline (Determined by a Central Laboratory) for Parts 1 and 2
Time frame: From Baseline (Days -28 to -1) through 90 days of the last dose of study drug (approximately 37 months)
Observed Serum Concentration at the Time of End of Infusion (CEOI) of Oleclumab (MEDI9447) Over Time
Time frame: Predose (within 90 minutes prior to start of infusion) and postdose (10 minutes after the end of infusion) on Days 1 and 57
Observed Lowest Serum Concentration (Ctrough) of MEDI9447 Over Time
Time frame: Predose (within 90 minutes prior to start of infusion) on Day 57
Maximum Plasma Concentration (Cmax) of Osimertinib and Its Metabolite (AZ5104)
Time frame: Predose (within 90 minutes prior to start of infusion) and postdose (1, 2, and 4 hours) on Days 1 and 29
Cmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X)
Time frame: Predose (within 90 minutes prior to start of infusion) and postdose (1, 2, 4, 6, and 24 hours) on Days 1 and 57
Tmax of AZD4635 and Its Metabolites (SSP-005173X and SSP-005174X)
Time frame: Predose (within 90 minutes prior to start of infusion) and postdose (1, 2, 4, 6, and 24 hours) on Days 1 and 57
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)
Time frame: Predose (within 90 minutes prior to start of infusion) and postdose (1, 2, 4, 6, and 24 hours) on Days 1 and 57
Number of Participants With Positive Post-baseline for Anti-oleclumab Antibodies
Time frame: 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)

Results and safety

Results posted to the registry on 26 Jul 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Oleclumab Dose 1 + Osimertinib Dose 1	5	0
Oleclumab Dose 2 + Osimertinib Dose 1	21	0
Oleclumab Dose 1 + AZD4635 Dose 1	6	0
Oleclumab Dose 1 + AZD4635 Dose 2	6	0
Oleclumab Dose 2 + AZD4635 Dose 2	5	0

Primary outcome: Number of Participants With Dose-limiting Toxicities (DLTs) in Part 1

Time frame: From Day 1 to Day 28 after first dose of study drug. Count of participants. Unit: Participants

Measure	Oleclumab Dose 1 + Osimertinib Dose 1 n = 3	Oleclumab Dose 2 + Osimertinib Dose 1 n = 4	Oleclumab Dose 1 + AZD4635 Dose 1 n = 3	Oleclumab Dose 1 + AZD4635 Dose 2 n = 5	Oleclumab Dose 2 + AZD4635 Dose 2 n = 4
Value	0	0	1	0	0

Population analysed: The DLT-evaluable population included all participants who enrolled in the dose-escalation phase, received all planned doses of oleclumab and at least 75% of the daily administrations of osimertinib or AZD4635 during the DLT-evaluation period and completed the safety follow-up through the DLT-evaluation period or experienced any DLTs.

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

Time frame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months). Count of participants. Unit: Participants

Measure	Oleclumab Dose 1 + Osimertinib Dose 1 n = 5	Oleclumab Dose 2 + Osimertinib Dose 1 n = 21	Oleclumab Dose 1 + AZD4635 Dose 1 n = 6	Oleclumab Dose 1 + AZD4635 Dose 2 n = 6	Oleclumab Dose 2 + AZD4635 Dose 2 n = 5
Any TEAEs	5	21	6	5	5
Any TESAEs	3	6	4	1	3

Population analysed: As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.

Primary outcome: Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Parts 1 and 2

Time frame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months). Count of participants. Unit: Participants

Measure	Oleclumab Dose 1 + Osimertinib Dose 1 n = 5	Oleclumab Dose 2 + Osimertinib Dose 1 n = 21	Oleclumab Dose 1 + AZD4635 Dose 1 n = 6	Oleclumab Dose 1 + AZD4635 Dose 2 n = 6
Anaemia	2	0	1	1
Neutropenia	1	1	0	0
Alanine aminotransferase increased	0	2	0	0
Amylase increased	1	0	0	0
Aspartate aminotransferase increased	0	3	0	0
Blood alkaline phosphatase increased	0	2	0	0
Blood creatinine increased	1	0	0	0
Lipase increased	1	0	0	0

Population analysed: As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.

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

Time frame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months). Count of participants. Unit: Participants

Measure	Oleclumab Dose 1 + Osimertinib Dose 1 n = 5	Oleclumab Dose 2 + Osimertinib Dose 1 n = 21	Oleclumab Dose 1 + AZD4635 Dose 1 n = 6	Oleclumab Dose 2 + AZD4635 Dose 2 n = 5
Hypertension	1	0	0	0
Hypotension	1	0	0	0
Pyrexia	0	1	0	0
Hypoxia	0	0	1	1

Population analysed: As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.

13 secondary outcomes are reported in the full results.

Adverse events

Time frame: From Day 1 through 90 days of the last dose of study drug (approximately 37 months). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Oleclumab Dose 1 + Osimertinib Dose 1	3 of 5 (60%)	5 of 5 (100%)	2 of 5
Oleclumab Dose 2 + Osimertinib Dose 1	6 of 21 (28.6%)	21 of 21 (100%)	9 of 21
Oleclumab Dose 1 + AZD4635 Dose 1	4 of 6 (66.7%)	6 of 6 (100%)	3 of 6
Oleclumab Dose 1 + AZD4635 Dose 2	1 of 6 (16.7%)	5 of 6 (83.3%)	2 of 6
Oleclumab Dose 2 + AZD4635 Dose 2	3 of 5 (60%)	5 of 5 (100%)	3 of 5

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36641093Kim 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.
D6070C00004 redacted protocolLink provided by the sponsor.
D6070C00004 SAP redactedLink provided by the sponsor.
D6070C00004 CSR Synopsis redactedLink provided by the sponsor.
Individual participant dataSharing planned: Yes. 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

MedImmune LLC study director

MedImmune LLC

13 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Oleclumab, Osimertinib and AZD4635 in people with Carcinoma, Non-Small-Cell Lung, run by MedImmune LLC at 13 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 23 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States, South Korea, Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose-limiting Toxicities (DLTs) in Part 1 (time frame: From Day 1 to Day 28 after first dose of study drug). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03381274, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2026.