Osimertinib Plus Chemotherapy vs Osimertinib in EGFRm NSCLC With Persistence Week-3 ctDNA EGFRm After 1L Osimertinib

NCT04769388 | Active Not Recruiting Phase 2

• 1 other identifier: ESR-19-20439
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Progression-free survival (PFS) using Investigator assessment as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

  The primary analysis of Progression-free survival (PFS) based on investigator assessment will occur when PFS maturity is observed at approximately 30 months after the first patient is randomized.

Secondary Outcomes (7)

• OS rate at 18 months

  The OS rate at 18 months will be defined as the Kaplan-Meier estimate of OS at 18 months.

• Objective Response Rate (ORR)

  Objective Response Rate analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 30 months from the first patient being randomized.

• Disease Control Rate (DCR)

  Disease control rate analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 30 months from the first patient being randomized.

• Duration of Response (DoR)

  Duration of Response analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 30 months from the first patient being randomized.

• Depth of Response

  Depth of Response analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 30 months from the first patient being randomized.

Study Arms (2)

Osimertinib 80 mg QD and platinum-based chemotherapy

EXPERIMENTAL

Osimertinib 80 mg in combination with pemetrexed (500 mg/m2) plus carboplatin (AUC5) on Day 1 of 21day cycles (every 3 weeks) for up to 6 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks.

Drug: Osimertinib; Drug: Pemetrexed/Carboplatin

Osimertinib 80mg QD

ACTIVE COMPARATOR

All patients randomized into this will only receive Osimertinib 80mg.

Drug: Osimertinib

Interventions

Osimertinib DRUG

Pemetrexed (500 mg/m2) plus carboplatin (AUC5) on Day 1 of 21day cycles (every 3 weeks) for up to 6 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks.

Also known as: AZD9291, Tagrisso

Osimertinib 80 mg QD and platinum-based chemotherapy; Osimertinib 80mg QD

Pemetrexed/Carboplatin DRUG

Pemetrexed (500 mg/m2) plus carboplatin (AUC5) on Day 1 of 21day cycles (every 3 weeks) for up to 6 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks.

Osimertinib 80 mg QD and platinum-based chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• History of EGFRm (exon 19 deletion or exon 21 L858R) in the plasma ctDNA by the local testing methods.
• 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.
• 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:
• Patients without disease progression by RECIST 1.1 evaluation;
• At least 1 measurable extracranial lesion according to RECIST 1.1 .
• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: collaborator
• Beijing Cancer Prevention & Treatment Society: lead

Study Sites (1)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib; Pemetrexed; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2021
• First Posted: February 24, 2021
• Study Start: December 28, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)