Osimertinib Alone or With Chemotherapy for EGFR-Mutant Lung Cancers
This study is comparing two treatments for metastatic non-small cell lung cancer that has an EGFR gene mutation. You would receive either osimertinib alone, which is the usual treatment, or osimertinib combined with chemotherapy (carboplatin and pemetrexed). Researchers want to see if adding chemotherapy helps stop the cancer from growing or spreading more effectively than osimertinib alone. To join, you must be at least 18 years old, have metastatic non-small cell lung cancer with an EGFR mutation, and either not have started EGFR TKI therapy or have started osimertinib within three weeks of enrollment. The main goal is to see how long people live without their cancer getting worse (progression-free survival) over two years. The study is currently recruiting 571 participants.
- Study design
- This is an interventional study where participants are randomly assigned to one of two treatment groups after an initial period on osimertinib. It aims to enroll 571 participants.
- What's involved
- Participants will start with three cycles of osimertinib alone. After this, if certain criteria are met, they will be randomly assigned to continue osimertinib alone or add carboplatin and pemetrexed chemotherapy for four cycles.
- Compensation
- Not stated in the trial record.
- Follow-up
- The primary endpoint measures progression-free survival at 2 years, suggesting follow-up will occur for at least this duration.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT04410796
Osimertinib Alone or With Chemotherapy for EGFR-Mutant Lung Cancers
Recruiting
PHASE2Ages 18+InterventionalTreatmentMemorial Sloan Kettering Cancer CenterInvestigator-initiated
~571 participants
Updated 2026-08-12 on ClinicalTrials.gov
What's tested:OsimertinibCarboplatinPemetrexed
At a glance
Recruiting sites
15 of 18 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Determine the progression-free survival
Measured over 2 years
Conditions
Where it's being run
18 sites across 9 statesNew York6
New Jersey4
California2
Florida1
Maryland1
Massachusetts1
Tennessee1
Texas1
Study leadership
- Helena Yu, MD · PRINCIPAL_INVESTIGATOR · Memorial Sloan Kettering Cancer Center
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Age ≥ 18 years
Biopsy proven metastatic non-small cell lung cancer, confirmed at enrolling institution
Somatic activating mutation in EGFR in pre-treatment tumor biopsy/ cytology from pleural fluid or cfDNA
Either have not started a prior EGFR TKI therapy or may have started osimertinib within 3 weeks of confirming eligibility and enrollment criteria of measurable disease per approval of PI, with no prior chemotherapy for treatment of metastatic disease (adjuvant therapy \> 6 months prior to study start is acceptable)
Measurable (RECIST 1.1) indicator lesion not previously irradiated with measurable disease determined per treating investigator. If a patient has already started on osimertinib there must be available pre-osimertinib baseline tumor assessments , or tumor assessments within +7 days of Osimertinib start, to be utilized for RECIST 1.1 assessment.
Karnofsky performance status (KPS)≥70%,
Ability to swallow oral medications
Adequate organ function (use of G-CSF and/or transfusion to meet these criteria are not allowed)
Hemoglobin ≥ 9 g/dL
Platelets ≥ 150,000mm\^3 or 150 x 10\^9/L
AST, ALT ≤ 2.5 x ULN with no liver metastases or \< 5x ULN with the presence of liver metastases
Total bilirubin ≤ 1.5 x ULN if no liver metastases or \< 3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases
Absolute neutrophil count (ANC) ≥ 1500 cells/mm\^3
Creatinine ≤ ULN OR calculated creatinine clearance ≥ 60ml/min calculated by Cockcroft and Gault equation
Creatinine clearance ≥ 60 mL/min calculated by Cockcroft and Gault equation
Willing to use highly effective contraceptive measures if of child-bearing potential or if the patient's sexual partner is a woman of child-bearing potential:
Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding prior to start of dosing through 6 weeks after discontinuing the study drug if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments
Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution
Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
Male subjects should be willing to use barrier contraception and avoid sperm donation prior to the start of dosing through 4 months of discontinuing the study drug
Patients with detectable plasma EGFR mutations at C2D1
Karnofsky performance status (KPS) ≥ 70%
Adequate organ function
Hemoglobin ≥ 9 g/dL
Platelets ≥ 100,000mm\^3 or 100 x 10\^9/L
Creatinine ≤ ULN OR calculated creatinine clearance ≥ 60ml/min
AST, ALT ≤ 3x ULN with no liver metastases or ≤ 5x ULN with the presence of liver metastases
Total bilirubin ≤ 1.5 x ULN if no liver metastases or ≤ 3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases
Absolute neutrophil count (ANC) ≥ 1500 cells/mm3Must have at least stable disease per RECIST 1.1 assessment prior to initiating chemotherapy at C4D1
Eligibility testing (KPS, bloodwork) should be tested at C3D1. If the subject's evaluation does not meet eligibility criteria, any result obtained between C3 and C4 can be used
Exclusion
Pregnant or lactating women
Any radiotherapy within 1 week prior to starting treatment on protocol. The washout window only applies for patients who have not started Osimertinib.
Any major surgery within 2 weeks of starting treatment on protocol. The washout window only applies for patients who have not started Osimertinib.
Any evidence of clinically significant interstitial lung disease
Treatment with an investigational drug within five half-lives of the compound or 3 months, whichever is greater
Currently receiving (or unable to stop prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4. All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4.
Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment, with the exception of alopecia and grade 2 prior platinum-therapy- related neuropathy
Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial
active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
Screening for chronic conditions is not required.
In patients with resolved or chronic hepatitis B infection (inactive carrier state) or active controlled HBV infection on treatment with osimertinib
Recommend monthly monitoring of ALT/AST, HBV DNA levels and HBsAg (if negative at baseline)
Where liver signs and symptoms of viral reactivation appear (HBV DNA levels exceeding 10-fold from baseline or ≥100 IU/ml (if baseline HBV DNA levels are undetectable) or conversion of HBsAg negative to positive):
Expert hepatologist/specialist oversight of the patient is required
Consider interruption or discontinuation of study treatment, based on riskbenefit assessment
Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the tablets or previous significant bowel resection that would preclude adequate absorption of osimertinib.
Any of the following cardiac criteria:
Mean resting corrected QT interval (QTc) \> 470 msec where QT interval is corrected for heart rate using Frederica's formula (QTcF).
Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block.
Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities (including: Serum/Plasma potassium \<LLN, Serum/Plasma Magnesium \<LLN; Serum/Plasma Calcium \<LLN), congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes.If concomitant medication can not be discontinued, please notify and confirm with MSK PI prior to enrollment.
Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib.
Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
What this trial measures
- Determine the progression-free survival2 years
As the primary endpoint for the treatment comparison, it is the duration of time from randomization to the time of disease progression (in the CNS or systemically) or death. In addition, as a secondary endpoint, PFS is measured from the start of treatment to disease progression or death. Intracranial progression-free survival (PFS) is defined as the duration of time from time of randomization to time of progression (in the CNS) or death, whichever occurs first. Overall survival (OS) is defined as the duration of time from first treatment to time of death.