A Study of Osimertinib-based Adaptive Treatment Guided by ctDNA EGFRm+ Monitoring in NSCLC

NCT07058519 | Recruiting Phase 2

• 1 other identifier: ESR-24-22779
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this adaptive, interventional study is to assess the efficacy and safety of osimertinib-based adaptive treatment based on ctDNA dynamic monitoring in locally advanced or metastatic EGFRm NSCLC participants with ctDNA EGFRm clearance after osimertinib plus chemotherapy. The main questions it aims to answer are: 1) PFS during adaptive treatment period in Cohort 1 defined as from initiation of Osimertinib in adaptive period to progression per investigator assessment; 2) Time from initiation of osimertinib in adaptive period to first ctDNA EGFRm relapse or death

Conditions

Locally Advanced or Metastatic EGFRm Non-small Cell Lung Cancer (NSCLC)

Keywords

NSCLC; EGFRm+; Osimertinib

Outcome Measures

Primary Outcomes (2)

• Progression-Free Survival (PFS) in Cohort 1

  Progression-Free Survival (PFS) is defined as the time from the first dose of osimertinib during the adaptive treatment period to the first documentation of disease progression based on investigator assessment according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, or death from any cause, whichever occurs first.

  From initiation of osimertinib in the adaptive therapy period until radiological disease progression or death (up to 33 months).

• Time to First ctDNA EGFRm Relapse or Death in Cohort 1

  Time to ctDNA EGFR mutation-positive (EGFRm) relapse is defined as the time from the start of osimertinib treatment in the adaptive therapy period to the first detection of EGFRm in plasma circulating tumour DNA (ctDNA), as assessed by Super ARMS PCR, or death from any cause, whichever occurs first.

  From initiation of osimertinib in the adaptive therapy period until ctDNA EGFR mutation relapse or death (up to 33 months)

Secondary Outcomes (6)

• Overall Survival (OS) in Cohort 1

  From initiation of osimertinib in adaptive therapy period until death (up to 33 months)

• Cumulative Duration of Chemotherapy Holiday in Cohort 1

  From start of adaptive therapy to disease progression or death (up to 33 months)

• Progression-Free Survival (PFS) in Cohort 2

  From initiation of maintenance therapy to radiological disease progression or death (up to 33 months)

• Overall Survival (OS) in Cohort 2

  From initiation of maintenance therapy to death (up to 33 months)

• Change from Baseline in Health-Related Quality of Life Scores (EORTC QLQ-C30)

  From baseline through end of treatment (up to 33 months)

Other Outcomes (3)

• Frequency of ctDNA EGFRm Relapse During Osimertinib Monotherapy in Cohort 1

  From start of osimertinib monotherapy to disease progression or switch to combination therapy (up to 33 months)

• Correlation Between ctDNA EGFRm Relapse and Disease Progression Events

  From adaptive therapy initiation to progression (up to 33 months)

• Acquired Resistance Mechanisms at Disease Progression

  At time of disease progression (up to 33 months)

Study Arms (2)

Cohort 1 (EGFRm ctDNA Clearance Group)

EXPERIMENTAL

EGFRm ctDNA Clearance Group

Drug: Osimertinib-based adaptive treatment

Cohort 2 (ctDNA EGFRm non-clearance group)

EXPERIMENTAL

Drug: Osimertinib 80 MG

Interventions

Osimertinib-based adaptive treatment DRUG

Participants in Cohort 1 will receive Osimertinib-based adaptive treatment (either Osimertinib monotherapy or Osimertinib plus chemotherapy) depending on ctDNA EGFRm clearance or relapse by ctDNA EGFRm dynamic monitoring, until radiological disease progression (PD) as per RECIST v1.1 or other withdrawal criteria are met.

Cohort 1 (EGFRm ctDNA Clearance Group)

Osimertinib 80 MG DRUG

Participants in Cohort 2 will receive Osimertinib 80 mg once daily (QD) plus pemetrexed maintenance every 3 weeks (Q3W) until radiological PD as per RECIST v1.1 or other withdrawal criteria are met.

Cohort 2 (ctDNA EGFRm non-clearance group)

Eligibility Criteria

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

You may qualify if:

• Provision of signed and dated, written informed consent form (ICF) prior to any study specific procedures.
• Male or female participants aged 18 years old and above.
• ECOG PS of 0-1.
• Life expectancy of at least 3 months at recruitment.
• Participants able to collect plasma samples at baseline.
• Newly diagnosed, and histologically documented locally advanced or metastatic non-squamous NSCLC with sensitizing EGFR mutations positive (either Exon 19 deletion or 21 L858R, confirmed by histology or cytology), and classified as stage IIIB, IIIC, IV or recurrent NSCLC which are not amenable to curative surgery or radiotherapy (per Version 8 of the International Association for the Study of Lung Cancer \[IASLC\] Staging Manual in Thoracic Oncology).
• Detectable EGFRm (Ex19del or L858R) in plasma ctDNA by central Super ARMS PCR testing at the time of screening.
• Participants must have untreated advanced NSCLC and intend to receive osimertinib plus chemotherapy as first-line treatment. Prior adjuvant and neo-adjuvant therapies (chemotherapy, radiotherapy, immunotherapy, biologic therapy, investigational agents), or definitive radiation/chemoradiation with or without regimens including immunotherapy, biologic therapy, investigational agents, are permitted as long as treatment was completed at least 12 months prior to receiving the first dose of study treatment.
• Participants with asymptomatic and stable central nervous system (CNS) metastases for at least 2 weeks (for those who received definitive therapy and steroids, a stable neurological status for at least 2 weeks after completion of the treatment is required) will be allowed, including leptomeningeal metastases.
• At least 1 lesion, not previously irradiated that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have a short axis of ≥15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI), and that is suitable for accurate repeated measurements. If only 1 measurable lesion exists, it is acceptable to be used (as a target lesion) as long as it has not been previously irradiated and as long as it has not been biopsied within 14 days of the baseline tumour assessment scans.
• Demonstrated absence of hepatitis C virus (HCV) co-infection or history of HCV co-infection
• Demonstrated absence of human immunodeficiency virus (HIV) infection
• Participants with active HBV infection are eligible if they are:
• Receiving anti-viral treatment for at least 6 weeks prior to study treatment, HBV DNA is suppressed to \<100 IU/mL and transaminase levels are below upper limit of normal (ULN).
• Participants with a resolved or chronic HBV infection are eligible if they are:

You may not qualify if:

• Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
• 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 participant to participate in the trial or which would jeopardize compliance with the protocol, or active infection (e.g. participants receiving treatment for infection) including hepatitis C and HIV, or active uncontrolled HBV infection. Screening for chronic conditions is not required.
• Any of the following cardiac criteria:
• Mean resting corrected QTc \>470 msec, obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value.
• 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 electrolyte abnormalities including:
• Serum/plasma magnesium\* \< LLN
• Serum/plasma calcium\* \< LLN
• Hypokalaemia\* ≥ CTCAE Grade 2 heart failure, 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 Torsade de Pointes.
• Correction of electrolyte abnormalities should be documented prior to first dose
• Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
• Absolute neutrophil count (ANC) \<1.5 × 109/L
• Platelet count \<100 × 109/L
• Hemoglobin \<90 g/L
• Alanine aminotransferase (ALT) \>2.5 times the ULN if no demonstrable liver metastases or \>5 times ULN in the presence of liver metastases.

Sponsors & Collaborators

• Shanghai Chest Hospital: lead
• AstraZeneca: collaborator

Study Sites (1)

Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University

Shanghai, Shanghai Municipality, 200030, China

RECRUITING

MeSH Terms

Interventions

osimertinib

Central Study Contacts

Shun Lu, PhD

CONTACT

86-21-6282199; shunlu@sjtu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Chief of Shanghai Lung Cancer Center

Study Record Dates

• First Submitted: June 16, 2025
• First Posted: July 10, 2025
• Study Start: September 23, 2025
• Primary Completion (Estimated): January 24, 2029
• Study Completion (Estimated): January 24, 2029
• Last Updated: November 26, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)