Osimertinib + Chemotherapy for Lung Cancer
Recruiting in Palo Alto (17 mi)
+19 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Memorial Sloan Kettering Cancer Center
Must not be taking: CYP3A4 inducers
Disqualifiers: Pregnancy, Interstitial lung disease, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 2 Jurisdictions
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
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.
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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
Trial 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 (Alkylating agents)
- Osimertinib (Tyrosine Kinase Inhibitor)
- Pemetrexed (Anti-metabolites)
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
Research Locations NearbySelect from list below to view details:
Columbia University (Data Collection Only)New York, NY
University of Washington (Data Collection Only)Seattle, WA
Sarah Cannon Research InstituteNashville, TN
MD ANDERSON CANCER CENTER (Data Collection Only)Houston, TX
More Trial Locations
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Who Is Running the Clinical Trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
Guardant Health, Inc.Industry Sponsor
AstraZenecaIndustry Sponsor
GUARDANT HEALTHCollaborator
References
Pancytopenia During Osimertinib Treatment in a Patient with EGFR-Mutated Non-Small Cell Lung Cancer. [2022]Osimertinib is an irreversible tyrosine kinase inhibitor approved for the treatment of metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). In clinical trials, osimertinib has exhibited excellent activity and less toxicity compared to gefitinib, erlotinib and standard chemotherapy.
Osimertinib: A Review in Completely Resected, Early-Stage, EGFR Mutation-Positive NSCLC. [2022]Osimertinib (TAGRISSO®) is an orally administered, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that is approved for the adjuvant treatment of adults with completely resected, stage IB-IIIA, EGFR sensitizing mutation (exon 19 deletion or exon 21 [L858R] substitution)-positive non-small cell lung cancer (NSCLC). In the pivotal ADAURA trial in adults with completely resected, early-stage, EGFR mutation-positive (EGFRm+) NSCLC, osimertinib adjuvant therapy significantly prolonged disease-free survival (DFS) compared with placebo in the overall population of patients with stage IB-IIIA disease, as well as in the primary population of patients with stage II-IIIA disease. A DFS benefit of osimertinib was seen irrespective of whether or not patients received prior adjuvant chemotherapy. Overall survival (OS) data were very immature at the time of the analysis of DFS, and more mature OS data are awaited with interest. Osimertinib adjuvant therapy did not adversely affect health-related quality of life and was generally well tolerated, with a manageable safety profile and no new safety signals identified. Based on the available evidence, osimertinib is thus an appropriate targeted option for the adjuvant treatment of adults with completely resected, stage IB-IIIA, EGFRm+ NSCLC.
Osimertinib as first-line therapy in advanced NSCLC: a profile of its use. [2020]Osimertinib (Tagrisso®) is an oral, CNS-active, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that selectively inhibits EGFR TKI-activating mutations over wild-type EGFR in patients with advanced non-small cell lung cancer (NSCLC), including the T790M mutation that often underlies acquired resistance to earlier generation EGFR TKIs. Relative to standard of care first-generation EGFR TKIs (erlotinib or gefitinib) as first-line treatment of EGFR activating mutation-positive advanced NSCLC, osimertinib significantly prolongs median progression-free survival (PFS), with separation of the Kaplan-Meier PFS survival curves evident by the first assessment timepoint of 6 weeks. Osimertinib prolongs PFS relative to standard EGFR TKI therapy in all prespecified groups, irrespective of the EGFR mutation present at study entry and presence of CNS metastases at study entry. Overall survival data are not yet mature. Osimertinib has a generally manageable tolerability profile.
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]Osimertinib is effective in non-small-cell lung cancer (NSCLC) with an acquired epidermal growth factor receptor (EGFR) T790M mutation, the most common resistance mechanism to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs).
Targeting the Gatekeeper: Osimertinib in EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. [2022]In 2015, the FDA approved an unprecedented number of new therapies for non-small cell lung cancer (NSCLC), among them therapies addressing specific genomic tumor subsets in the setting of development of resistance to first-line targeted therapy. Osimertinib (Tagrisso, formerly AZD9291; AstraZeneca) is indicated for patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, who have progressed on or after EGFR tyrosine kinase inhibitor therapy. It received breakthrough therapy designation, priority review status, and accelerated approval from the FDA. Clin Cancer Res; 23(3); 618-22. ©2016 AACR.
Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. [2022]On November 13, 2015, the FDA granted accelerated approval to osimertinib (TAGRISSO; AstraZeneca), a breakthrough therapy-designated drug for the treatment of patients with metastatic EGFR T790M mutation-positive non-small cell lung cancer, as detected by an FDA-approved test, with progression on or after EGFR tyrosine kinase inhibitor therapy. Approval was based on durable tumor response rates in two single-arm, multicenter trials: the dose extension cohort of a first-in-human trial (FIH; AURA extension; n = 201) and a fixed-dose, activity-estimating trial (AURA2; n = 210). Osimertinib was administered at 80 mg orally once daily. The objective response rates (ORR) per blinded independent committee review were 57% [95% confidence interval (CI), 50-64) in AURA extension and 61% (95% CI, 54-68) in AURA2. Median duration of response (DOR) could not be estimated. Supportive efficacy data from 63 patients in the dose-finding part of the FIH trial demonstrated an ORR of 51% (95% CI, 38-64), with a median DOR of 12.4 months. Common adverse events (AE) evaluated in 411 patients included diarrhea (42%), rash (41%), dry skin (31%), and nail toxicity (25%). Grade 3 to 4 AEs occurred in 28% of patients, and 5.6% discontinued treatment due to AEs. Clin Cancer Res; 23(9); 2131-5. ©2016 AACR.
New Adjuvant Drug for Lung Cancer. [2023]A new adjuvant treatment, osimertinib (Tagrisso), has been approved for patients with non-small cell lung cancer whose tumors have certain mutations.The most common adverse effects of treatment are leukopenia, lymphopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough.
Osimertinib: First Global Approval. [2022]Osimertinib (Tagrisso(™), AZD9291) is an oral, third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that is being developed by AstraZeneca for the treatment of advanced non-small cell lung cancer (NSCLC). Osimertinib has been designed to target the EGFR T790M mutation that is often present in NSCLC patients with acquired EGFR TKI resistance, while sparing wild-type EGFR. In November 2015, the tablet formulation of osimertinib was granted accelerated approval in the USA for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC (as detected by an FDA-approved test) who have progressed on or after EGFR TKI therapy. Osimertinib has also been granted accelerated assessment status for this indication in the EU, and is in phase III development for first- and second-line and adjuvant treatment of advanced EGFR mutation-positive NSCLC in several countries. Phase I trials in patients with advanced solid tumours are also being conducted. This article summarizes the milestones in the development of osimertinib leading to this first approval for NSCLC.
Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. [2022]Osimertinib (AZD9291) is an oral, potent, irreversible EGFR tyrosine-kinase inhibitor selective for EGFR tyrosine-kinase inhibitor sensitising mutations, and the EGFR Thr790Met resistance mutation. We assessed the efficacy and safety of osimertinib in patients with EGFR Thr790Met-positive non-small-cell lung cancer (NSCLC), who had progressed after previous therapy with an approved EGFR tyrosine-kinase inhibitor.
Increased Expression of IRE1α Associates with the Resistant Mechanism of Osimertinib (AZD9291)-resistant non-small Cell Lung Cancer HCC827/OSIR Cells. [2022]Osimertinib (OSI), also known as AZD9291, is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of non-small cell lung cancer (NSCLC) patients.