571 Participants Needed

Osimertinib + Chemotherapy for Lung Cancer

Recruiting at 19 trial locations
HY
GR
Overseen ByGregory Riely, MD, PhD
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Memorial Sloan Kettering Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise
Approved in 2 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

This study will compare the effectiveness of osimertinib alone with the combination of osimertinib and chemotherapy (carboplatin and pemetrexed) in people with metastatic lung cancer that has a change (mutation) in the gene EGFR. Osimertinib alone is the usual treatment for metastatic EGFR-mutant lung cancer. Researchers think adding chemotherapy to osimertinib could possibly add to the anticancer effects of the usual treatment and help stop cancer from growing or spreading.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications or herbal supplements known to strongly induce CYP3A4 before starting the study treatment. It's important to discuss your current medications with the study team to ensure they don't interfere with the trial.

What data supports the effectiveness of the drug Osimertinib for lung cancer?

Osimertinib is effective in treating non-small cell lung cancer (NSCLC) with specific genetic mutations, as it significantly prolongs the time patients live without the disease getting worse compared to older treatments. It is particularly beneficial for patients with certain mutations that make them resistant to earlier treatments.12345

Is the combination of Osimertinib and Chemotherapy safe for humans?

Osimertinib, used for certain types of lung cancer, is generally well tolerated with common side effects like diarrhea, rash, and dry skin. Serious side effects occurred in about 28% of patients, and 5.6% stopped treatment due to these effects. No new safety concerns were identified in recent studies.25678

What makes the drug Osimertinib unique for lung cancer treatment?

Osimertinib is unique because it is a third-generation drug specifically designed to target a mutation (EGFR T790M) that often causes resistance to earlier treatments in non-small cell lung cancer. It is taken orally and has been shown to significantly prolong disease-free survival in patients with certain genetic mutations.258910

Research Team

Helena A. Yu, MD - MSK Thoracic Medical ...

Helena Yu, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults over 18 with metastatic non-small cell lung cancer and a specific EGFR mutation. They must be able to swallow pills, have not had certain treatments before, and their organs must function well. Pregnant women or those with significant health issues like interstitial lung disease or uncontrolled diseases are excluded.

Inclusion Criteria

I am willing to use effective birth control if I or my partner can become pregnant.
My lung cancer has spread and was confirmed with a biopsy.
I can swallow pills.
See 6 more

Exclusion Criteria

I don't have severe side effects from past treatments, except for hair loss or mild nerve pain from platinum-based therapy.
I am taking or can't stop taking strong CYP3A4 inducers.
I do not have active infections like hepatitis B, C, or HIV.
See 11 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

3 weeks
1 visit (telemedicine acceptable)

Initial Treatment

Participants receive osimertinib monotherapy for 3 cycles (21 days per cycle) as standard care

9 weeks
3 visits (in-person or telemedicine)

Randomization/Treatment

Participants are randomized to continue osimertinib alone or add carboplatin/pemetrexed chemotherapy

12 weeks
4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

  • Carboplatin
  • Osimertinib
  • Pemetrexed
Trial OverviewResearchers are testing if adding chemotherapy (carboplatin and pemetrexed) to osimertinib, which is the usual treatment for this type of lung cancer, can better stop the cancer from growing compared to osimertinib alone.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Osimertinib plus Carboplatin and PemetrexedExperimental Treatment3 Interventions
All patients will receive osimertinib 80mg orally daily. Patients receive Carboplatin (AUC 5 IV q 3 weeks) and Pemetrexed (500mg/m2 IV q 3 weeks) for a total of 4 cycles followed by pemetrexed maintenance from cycle 8 onwards. Patients will be required to complete a pill diary beginning at Cycle 4.
Group II: Osimertinib aloneExperimental Treatment1 Intervention
All patients will receive osimertinib 80mg orally daily. Subjects randomized to Arm A may be dispensed osimertinib for 2 cycles from Cycle 4 onward. Patients will be required to complete a pill diary beginning at Cycle 4.

Osimertinib is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Tagrisso for:
  • Locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R mutations
  • Metastatic EGFR T790M mutation-positive NSCLC
🇪🇺
Approved in European Union as Tagrisso for:
  • Locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R mutations
  • Metastatic EGFR T790M mutation-positive NSCLC

Find a Clinic Near You

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials
1,998
Recruited
602,000+

Guardant Health, Inc.

Industry Sponsor

Trials
22
Recruited
66,900+

AstraZeneca

Industry Sponsor

Trials
4,491
Recruited
290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

GUARDANT HEALTH

Collaborator

Trials
5
Recruited
1,600+

Findings from Research

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]
Osimertinib significantly improves disease-free survival (DFS) in adults with completely resected, early-stage EGFR mutation-positive non-small cell lung cancer (NSCLC), as shown in the pivotal ADAURA trial, regardless of prior adjuvant chemotherapy.
The treatment is well tolerated with a manageable safety profile, and it does not negatively impact health-related quality of life, making it a suitable option for adjuvant therapy in this patient population.
Osimertinib: A Review in Completely Resected, Early-Stage, EGFR Mutation-Positive NSCLC.Frampton, JE.[2022]
Osimertinib is a third-generation EGFR tyrosine kinase inhibitor that effectively targets specific mutations in advanced non-small cell lung cancer (NSCLC), including the T790M mutation, leading to significantly longer progression-free survival compared to first-generation EGFR TKIs like erlotinib or gefitinib.
The benefits of osimertinib in prolonging progression-free survival were consistent across all patient groups, regardless of the type of EGFR mutation or the presence of CNS metastases, and it has a generally manageable safety profile.
Osimertinib as first-line therapy in advanced NSCLC: a profile of its use.Scott, LJ.[2020]

References

Pancytopenia During Osimertinib Treatment in a Patient with EGFR-Mutated Non-Small Cell Lung Cancer. [2022]
Osimertinib: A Review in Completely Resected, Early-Stage, EGFR Mutation-Positive NSCLC. [2022]
Osimertinib as first-line therapy in advanced NSCLC: a profile of its use. [2020]
Post-Progression Survival in Secondary EGFR T790M-Mutated Non-Small-Cell Lung Cancer Patients With and Without Osimertinib After Failure of a Previous EGFR TKI. [2022]
Targeting the Gatekeeper: Osimertinib in EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. [2022]
Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. [2022]
New Adjuvant Drug for Lung Cancer. [2023]
Osimertinib: First Global Approval. [2022]
Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. [2022]
Increased Expression of IRE1α Associates with the Resistant Mechanism of Osimertinib (AZD9291)-resistant non-small Cell Lung Cancer HCC827/OSIR Cells. [2022]