Osimertinib + Chemotherapy for Lung Cancer

Recruiting at 19 trial locations

Overseen By Gregory Riely, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: CYP3A4 inducers

Disqualifiers: Pregnancy, Interstitial lung disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

571 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treating metastatic lung cancer with a specific gene mutation (EGFR). Researchers compare the effectiveness of the usual treatment, osimertinib (a targeted therapy), alone versus in combination with chemotherapy. The aim is to determine if adding chemotherapy better controls the cancer's growth or spread. Individuals with metastatic lung cancer who have this specific EGFR mutation and have not received chemotherapy for it may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that osimertinib is generally safe for treating lung cancer with an EGFR mutation. In studies with patients, the drug was well-tolerated, with common side effects including mild skin rash and diarrhea. However, rare but serious risks, such as lung problems, can become severe if not monitored.

When combined with chemotherapy drugs (carboplatin and pemetrexed), research indicates this combination is also safe. Reports found that adding these chemotherapy drugs did not significantly increase severe side effects compared to using osimertinib alone. Some patients experienced side effects like nausea, low blood cell counts, and tiredness, which are typical with chemotherapy.

These findings suggest that both treatments are generally safe, with some manageable side effects. Participants in clinical trials must be closely monitored by healthcare providers to address any side effects that may arise. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about osimertinib treatments for lung cancer because they offer a unique approach compared to the current standard of care, which typically involves other EGFR inhibitors or chemotherapy alone. Osimertinib, a third-generation EGFR inhibitor, specifically targets and binds to mutant forms of the EGFR protein that are often resistant to first and second-generation EGFR inhibitors, making it effective even in cases where other treatments fail. Additionally, combining osimertinib with chemotherapy agents like carboplatin and pemetrexed could enhance its effectiveness by attacking the cancer through multiple pathways, potentially improving patient outcomes. These features make osimertinib a promising option for advancing lung cancer treatment.

What evidence suggests that this trial's treatments could be effective for metastatic EGFR-mutant lung cancer?

Research has shown that osimertinib effectively treats advanced lung cancer with a specific gene change called an EGFR mutation. Studies have found that when patients take osimertinib alone, their cancer typically does not worsen for about 20 months, a period known as "progression-free survival." In this trial, some participants will receive osimertinib alone, while others will receive it with chemotherapy drugs like carboplatin and pemetrexed. The combination has been linked to better results compared to osimertinib alone, potentially stopping cancer growth more effectively. Overall, both treatments are promising options being evaluated in this trial. ^{6 7 8 9 10}

Who Is on the Research Team?

Helena Yu, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Osimertinib
• Pemetrexed

Trial Overview Researchers 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.

How Is the Trial Designed?

Group I: Osimertinib plus Carboplatin and Pemetrexed Experimental Treatment 3 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 alone Experimental Treatment 1 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

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+

Published Research Related to This Trial

In a study of 240 advanced non-small-cell lung cancer (NSCLC) patients with acquired resistance to EGFR TKIs, 52.9% had the T790M mutation after rebiopsy, highlighting the mutation's prevalence in treatment resistance.

Patients with the T790M mutation who had previously used osimertinib experienced significantly longer post-progression survival (42.6 months) compared to those without osimertinib (18.0 months) or without the mutation (18.8 months), suggesting osimertinib's effectiveness as a standard treatment for T790M-positive NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Chiang, CL., Huang, HC., Shen, CI., et al.[2022]

The study established an osimertinib-resistant cell line (HCC827/OSIR) from EGFR-sensitive HCC827 cells, demonstrating that these resistant cells have higher resistance to multiple EGFR tyrosine kinase inhibitors compared to the original cells.

Increased expression of IRE1α was identified as a potential mechanism for resistance to osimertinib, and targeting IRE1α with an inhibitor showed promise in reducing the number of viable resistant cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased Expression of IRE1α Associates with the Resistant Mechanism of Osimertinib (AZD9291)-resistant non-small Cell Lung Cancer HCC827/OSIR Cells. Tang, ZH., Su, MX., Guo, X., et al.[2022]

Osimertinib (Tagrisso) is an approved adjuvant treatment for non-small cell lung cancer patients with specific tumor mutations, highlighting its targeted therapeutic approach.

Common side effects of osimertinib include blood-related issues like leukopenia and thrombocytopenia, as well as gastrointestinal and skin reactions, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Drug for Lung Cancer. Aschenbrenner, DS.[2023]

Osimertinib is an oral medication specifically designed to target the EGFR T790M mutation in advanced non-small cell lung cancer (NSCLC), which helps overcome resistance to previous EGFR TKI therapies.

It received accelerated approval in the USA in November 2015 for patients with metastatic EGFR T790M mutation-positive NSCLC who have progressed after EGFR TKI treatment, and is currently undergoing further development for broader treatment applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib: First Global Approval. Greig, SL.[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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib: A Review in Completely Resected, Early-Stage, EGFR Mutation-Positive NSCLC. Frampton, JE.[2022]

Osimertinib (TAGRISSO) received accelerated FDA approval for treating metastatic non-small cell lung cancer with the EGFR T790M mutation, showing significant tumor response rates of 57% and 61% in two major trials involving 411 patients.

While osimertinib demonstrated promising efficacy, common side effects included diarrhea (42%) and rash (41%), with 28% of patients experiencing severe adverse events, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. Khozin, S., Weinstock, C., Blumenthal, GM., et al.[2022]

In a phase 2 study involving 210 patients with EGFR Thr790Met-positive non-small-cell lung cancer (NSCLC), osimertinib demonstrated significant efficacy, with 70% of patients achieving an objective response, including 3% with complete responses.

Osimertinib was found to have manageable side effects, although serious adverse events occurred in 25% of patients, with interstitial lung disease being the only fatal event possibly related to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. Goss, G., Tsai, CM., Shepherd, FA., et al.[2022]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the Gatekeeper: Osimertinib in EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. Skoulidis, F., Papadimitrakopoulou, VA.[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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib as first-line therapy in advanced NSCLC: a profile of its use. Scott, LJ.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39118879/

Real-world efficacy of low dose osimertinib as second-line ... Treatment with low dose osimertinib demonstrated good efficacy and tolerability in EGFR-mutated advanced NSCLC patients who failed first-line treatment.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2306434

Osimertinib with or without Chemotherapy in EGFR- ... First-line treatment with osimertinib–chemotherapy led to significantly longer progression-free survival than osimertinib monotherapy among patients with EGFR- ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S246829422500036X

Real-world comparative outcomes of EGFR-TKIs for first- ... This study compared real-world clinical outcomes of 1L osimertinib versus 1st or 2nd generation EGFR-TKIs (1/2G-TKIs) in patients with EGFR+ mNSCLC.

4. jtocrr.org jtocrr.org/article/S2666-3643(24)00090-0/fulltext

The Whole Picture of First-Line Osimertinib for EGFR ... A total of 583 patients received osimertinib. The median progression-free and overall survival were 20.0 (95% confidence interval [CI]: 17.6– ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37840304/

Exploring the impact of patient-specific clinical features on ... Limited data exists on the impact of patient characteristics or osimertinib exposure on effectiveness outcomes. This was a Dutch, multicenter ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/208065s030lbl.pdf

TAGRISSO® (osimertinib) tablets, for oral use TAGRISSO is indicated as adjuvant therapy after tumor resection in adult patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth ...

7. tagrisso.com tagrisso.com/

TAGRISSO: Treatment for Certain Types of EGFR+ NSCLC Lung problems. TAGRISSO may cause severe lung problems that may lead to death. Symptoms may be similar to those symptoms from lung cancer. Tell your healthcare ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30194172/

Efficacy and Safety Data of Osimertinib in Elderly Patients ... Osimertinib is a safe and effective treatment option for elderly patients with advanced NSCLC who harbor the EGFR mutation.

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.20.01171

Cardiac Safety of Osimertinib: A Review of Data Osimertinib provided statistically significant superior median progression-free survival (PFS) and overall survival (OS) versus comparator EGFR-TKIs (erlotinib ...

10. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2024/tagrisso-osimertinib-with-the-addition-of-chemotherapy-approved-in-the-us-for-patients-with-egfr-mutated-advanced-lung-cancer.html

TAGRISSO (osimertinib) with the addition of chemotherapy ... Approval based on FLAURA2 results which showed TAGRISSO plus chemotherapy extended median progression-free survival by nearly 9 months vs.