osimertinib plus chemotherapy vs osimertinib in egfrm nsclc with persistence week-3 ctdna egfrm after 1l osimertinib

Conditions: Non Small Cell Lung Cancer

Summary: this is a prospective, randomised, open-label, positive-controlled study to investigate the efficacy and safety of osimertinib plus carboplatin/pemetrexed versus osimertinib monotherapy in metastatic egfrm nsclc patients with egfrm persistence in ctdna at 3 weeks after first-line therapy with osimertinib.


Eligibility criteria:
inclusion criteria: * provision and signed of informed consent prior to any study specific procedures; * male or female, aged at least 18 years; * eastern cooperative oncology group (ecog) performance-status score of 0 or 1; * newly diagnosed, and histologically documented metastatic non-squamous nsclc with sensitizing egfr mutations positive, and classified as stage iv or recurrent nsclc which are not amenable to curative surgery or radiotherapy; * life expectancy of at least 3 months at recruitment; * only the patients receiving osimertinib as 1l treatment and meeting the following criteria will be considered: a. prior to 1l osimertinib: 1. history of egfrm (exon 19 deletion or exon 21 l858r) in the plasma ctdna by the local testing methods. 2. no previous systemic treatment. adjuvant therapies, or definitive radiation/chemoradiation are permitted as long as treatment was completed at least 6 months prior to receiving 1l treatment. 3. patients with asymptomatic and stable cns metastases for at least 2 weeks will be allowed, including leptomeningeal metastases. b. prior to randomization: patients after 3 weeks of 1l osimertinib treatment who have persistence ctdna egfrm by superarms at 3 weeks will be considered to be enrolled. they will need to further meet the criteria below before randomization: 1. patients without disease progression by recist 1.1 evaluation; 2. at least 1 measurable extracranial lesion according to recist 1.1 . 3. 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 if of child-bearing potential, or must have evidence of non-child-bearing potential. 4. male subjects should be willing to agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm. exclusion criteria: * involvement in the planning and/or conduct of the study; * history of hypersensitivity to active or inactive excipients of osimertinib and/or pemetrexed and/or carboplatin or drugs with a similar chemical structure or class to osimertinib and/or pemetrexed and/or carboplatin; * for patients, inability to collect plasma samples at baseline and disease progression; * qt prolongation or any clinically important abnormalities in rhythm; * any evidence of severe or uncontrolled systemic diseases; * currently receiving medications or herbal supplements known to be strong inducers of cyp3a4; * any unresolved toxicities from prior therapy greater than ctcae 5.0 grade 1 at the time of starting study treatment. * refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib. * inadequate bone marrow reserve or organ function; * 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. * 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. * contraindication for osimertinib, pemetrexed and carboplatin according to china approved label. * women who are pregnant or breast-feeding.