43 Participants Needed

Combination Therapy for Non-Small Cell Lung Cancer

Recruiting at 12 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before starting. You must stop taking any EGFR TKI (a type of cancer drug) 14 days before the trial and any other cancer treatments 21 days before. Herbal supplements and medications that affect liver enzymes (CYP3A4) must also be stopped for Arm A.

Is the combination therapy for non-small cell lung cancer safe for humans?

Osimertinib (Tagrisso) has been studied for non-small cell lung cancer and is generally well tolerated, but it can cause side effects like diarrhea, rash, dry skin, and nail issues. Serious side effects occurred in about 28% of patients, and some stopped treatment due to these effects. Overall, it has a manageable safety profile with no new safety concerns identified.12345

How is the drug combination therapy for non-small cell lung cancer unique?

This combination therapy is unique because it includes osimertinib, a third-generation drug specifically designed to target the EGFR T790M mutation, which is a common cause of resistance to earlier treatments. Osimertinib is known for its effectiveness and lower toxicity compared to other treatments, making it a promising option for patients with specific genetic mutations in their cancer.46789

What data supports the effectiveness of the drug combination therapy for non-small cell lung cancer?

Osimertinib, a key component of the combination therapy, is effective for treating non-small cell lung cancer with specific EGFR mutations, as it has been shown to prolong survival and has received FDA approval for its use in these cases.4781011

Who Is on the Research Team?

ML

MedImmune LLC

Principal Investigator

MedImmune LLC

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced non-small cell lung cancer that has a specific mutation (EGFRm). Participants must have tried one EGFR inhibitor and can't be T790M positive. They should weigh at least 35 kg, be fairly active (ECOG of 0 or 1), and not have used certain medications recently. People with untreated brain metastases, recent heart issues, or autoimmune diseases in the last three years cannot join.

Inclusion Criteria

I weigh at least 35 kilograms.
My lung cancer is advanced or has spread, and tests show it has EGFR mutations.
I am fully active or can carry out light work.
See 2 more

Exclusion Criteria

I have had an autoimmune or inflammatory disorder in the last 3 years.
I have taken an EGFR inhibitor within the last 14 days.
I have had a blood clot in the last 3 months.
See 12 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-escalation Treatment

Participants receive intravenous oleclumab and oral AZD4635 or osimertinib in a dose-escalation format to determine safety and tolerability

4 weeks
Bi-weekly visits for intravenous administration

Dose-expansion Treatment

Participants receive the recommended phase 2 dose (RP2D) of oleclumab and osimertinib until disease progression or unacceptable toxicity

Until disease progression or unacceptable toxicity
Bi-weekly visits for intravenous administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days after the last dose of study drug

What Are the Treatments Tested in This Trial?

Interventions

  • AZD4635
  • MEDI9447
  • Oleclumab
  • Osimertinib
Trial Overview The study tests new combinations of drugs: Oleclumab with Osimertinib for those who've had one prior therapy, and Oleclumab with AZD4635 for those who've had two to four therapies. It aims to assess safety, tolerability, and how well these combos work against advanced EGFRm NSCLC.
How Is the Trial Designed?
5Treatment groups
Experimental Treatment
Group I: Oleclumab Dose 2 + Osimertinib Dose 1Experimental Treatment2 Interventions
Group II: Oleclumab Dose 2 + AZD4635 Dose 2Experimental Treatment2 Interventions
Group III: Oleclumab Dose 1 + Osimertinib Dose 1Experimental Treatment2 Interventions
Group IV: Oleclumab Dose 1 + AZD4635 Dose 2Experimental Treatment2 Interventions
Group V: Oleclumab Dose 1 + AZD4635 Dose 1Experimental Treatment2 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

MedImmune LLC

Lead Sponsor

Trials
348
Recruited
788,000+
Founded
1988
Headquarters
Gaithersburg, USA
Known For
Biologics research
Top Products
Synagis, FluMist
Dr. Reginald Seeto profile image

Dr. Reginald Seeto

MedImmune LLC

Chief Medical Officer since 2008

MD from University of Sydney, B.Sc. from University of Sydney

Peter Greenleaf profile image

Peter Greenleaf

MedImmune LLC

Chief Executive Officer since 2006

MBA from St. Joseph’s University, B.S. from Western Connecticut State University

Published Research Related to This Trial

Osimertinib (Tagrisso) is a targeted therapy approved by the FDA for patients with metastatic non-small cell lung cancer (NSCLC) who have the EGFR T790M mutation and have progressed after previous treatments.
The drug received special designations from the FDA, including breakthrough therapy and priority review, highlighting its significance in treating resistant forms of NSCLC.
Targeting the Gatekeeper: Osimertinib in EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer.Skoulidis, F., Papadimitrakopoulou, VA.[2022]
Osimertinib (AZD9291) is effective in prolonging survival for non-small cell lung cancer patients with EGFR mutations, but resistance to the drug is a common issue, prompting the need to explore resistance mechanisms.
In this study, AZD9291-resistant NSCLC cell lines were established, revealing significant changes in circular RNA (circRNA) expression profiles, which may contribute to drug resistance and could serve as potential targets for future gene therapies.
Comprehensive analysis of circular RNA profiling in AZD9291-resistant non-small cell lung cancer cell lines.Chen, T., Luo, J., Gu, Y., et al.[2022]
Osimertinib, an irreversible tyrosine kinase inhibitor, showed excellent activity in treating a 69-year-old man with metastatic EGFR-mutated non-small cell lung cancer, leading to a rapid treatment response despite initial severe pancytopenia.
After experiencing pancytopenia, the patient's dose of osimertinib was reduced from 80 mg to 40 mg daily, which allowed for continued effective treatment without further adverse events, demonstrating the potential for safe dose adjustments.
Pancytopenia During Osimertinib Treatment in a Patient with EGFR-Mutated Non-Small Cell Lung Cancer.Di Marino, P., Chiapperino, C., Primavera, FC., et al.[2022]

Citations

Targeting the Gatekeeper: Osimertinib in EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. [2022]
Comprehensive analysis of circular RNA profiling in AZD9291-resistant non-small cell lung cancer cell lines. [2022]
Pancytopenia During Osimertinib Treatment in a Patient with EGFR-Mutated Non-Small Cell Lung Cancer. [2022]
Increased Expression of IRE1α Associates with the Resistant Mechanism of Osimertinib (AZD9291)-resistant non-small Cell Lung Cancer HCC827/OSIR Cells. [2022]
Osimertinib making a breakthrough in lung cancer targeted therapy. [2020]
New Adjuvant Drug for Lung Cancer. [2023]
Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. [2022]
Phase Ib Study of Osimertinib Plus Ramucirumab in Japanese Lung Cancer Patients With EGFR Mutation. [2023]
Osimertinib: A Review in Completely Resected, Early-Stage, EGFR Mutation-Positive NSCLC. [2022]
Severe hepatotoxicity due to osimertinib after nivolumab therapy in patients with non-small cell lung cancer harboring EGFR mutation. [2022]
Phase 2 study of osimertinib in combination with platinum and pemetrexed in patients with previously untreated EGFR-mutated advanced non-squamous non-small cell lung cancer: The OPAL Study. [2023]
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