Real-world Experience With Combination Chemotherapy and Osimertinib in Poor Prognostic Group of Metastatic EGFR-mutated Lung Adenocarcinoma

NCT06918782 | Not Yet Recruiting Phase 2

• 1 other identifier: Osim-CT1LEGFR
• Study Type: interventional
• Target: 47
• Locations: 0 countries
• Sites: N/A

Brief Summary

The aims of this study are to determine the potential clinical benefits (in terms of PFS, objective response and OS) of add-on systemic chemotherapy (pemetrexed+carboplatin/cisplatin) to first-line osimertinib treatment among the poor prognostic group of metastatic EGFR-mutant lung adenocarcinoma, i.e. failure of plasma ctDNA EGFR mutant clearance at week 3 after osimertinib treatment

Conditions

Lung Cancer (NSCLC)

Keywords

Osimertinib; chemotherapy; ctDNA; advance stage lung cancer

Outcome Measures

Primary Outcomes (1)

• real-world 1-year progression-free survival

  The duration of osimertinib treatment extends from the initiation of therapy until either disease progression or death from any cause, whichever occurs first. Progression-free survival (PFS) will be monitored for up to 1 year.

Secondary Outcomes (5)

• rw response rate

  From date of initiation of osimertinib therapy (day 1) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months.

• OS

  From date of initiation of osimertinib therapy (day 1) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months.

• rw PFS

  The progression-free survival (PFS) will be assessed at the one-year mark.

• rw time-to-treatment discontinuation

  From date of initiation of osimertinib therapy (day 1) until the date of first documented discontinuation or date of death from any cause, whichever came first, through study completion, an average of 1 year.

• ctDNA clearance rate

  The plasma EGFR mutation ctDNA testing will be carried out by Cobas EGFR Mutation Test v2 (Roche Diagnostics) at baseline, 3, 6, 9 and 12 weeks of osimertinib treatment.

Study Arms (1)

Combination chemotherapy and osimertinib

EXPERIMENTAL

Incorporating chemotherapy with ongoing osimertinib treatment involves initiating osimertinib at the standard dose of 80mg orally once daily. This regimen includes a combination of pemetrexed and carboplatin or cisplatin administered intravenously every 3 weeks for a maximum of 6 cycles, followed by maintenance pemetrexed at a dosage of 500mg/m2 every 3 weeks in cases of non-progressive disease.

Drug: Osimertinib plus platinum doublet chemotherapy

Interventions

Osimertinib plus platinum doublet chemotherapy DRUG

Based on the FLAURA2 study (which was not subdivided into ctDNA clearance subgroups), it is hypothesized that adding systemic chemotherapy to osimertinib will prolong PFS and OS and increase objective response rate even among the poor prognostic subgroup with failed ctDNA clearance after initial osimertinib monotherapy. By incorporating systemic chemotherapy (pemetrexed/carboplatin) to first-line osimertinib treatment among the poor prognostic group of metastatic EGFR-mutant lung adenocarcinoma with failure of plasma ctDNA EGFR mutant clearance despite initial osimertinib treatment.

Combination chemotherapy and osimertinib

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults above 18 years old, both male and female;
• Pathologically confirmed lung adenocarcinoma with stage IIIB/C or IV disease (TNM staging version 8);
• Confirmed EGFR common sensitizing mutations (exon 21 L858R or exon 19 del) by locally approved molecular testing methods (allele-specific PCR or NGS) based on tumour tissues or plasma ctDNA;
• Clinically decided for first-line systemic treatment with osimertinib;
• Detectable pre-treatment plasma EGFR mutations (by Cobas EGFR Mutation Test v2) and failed clearance 3 weeks (+/- 5 days) after osimertinib treatment;
• At least one measurable target lesion by RECIST v1.1 criteria;
• Performance state (ECOG) ≤ 1 and life expectancy ≥ 12 weeks;
• Females in reproductive age with negative pregnancy test and highly effective means of contraception during and ≥ 4 months after intervention period;
• Males should agree to have highly effective means of contraception during and ≥ 4 months after intervention period; and
• Written informed consent obtained.

You may not qualify if:

• Mixed NSCLC and small cell carcinoma;
• Prior systemic anticancer treatment (targeted therapy, chemotherapy or immunotherapy) for metastatic stage NSCLC;
• Prior adjuvant chemotherapy or targeted therapy within 6 months;
• Local radiotherapy within 2 weeks or major surgery within 4 weeks;
• Inadequate haematological function (haemoglobin \< 9 g/dL, neutrophils \< 1.5 x 109/L, platelets \< 100 x 109/L), renal function (serum creatinine ≥ 1.5 x upper limit of normal (ULN) or creatinine clearance \< 45 ml/min) or liver function (total bilirubin \> 1.5 x ULN, ALT/AST/ALP \> 3 x ULN; ALT/AST/ALP \> 5 x ULN for liver metastases; ALP \> 5 x ULN for bone metastases);
• Major medical comorbidities with significant organ dysfunction;
• Known active hepatitis B or C infection. Chronic hepatitis B on antiviral allowed as per institutional guideline for chemotherapy;
• Malignancies other than NSCLC; and
• Known hypersensitivity to pemetrexed or carboplatin.

Sponsors & Collaborators

• The University of Hong Kong: lead

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib

Condition Hierarchy (Ancestors)

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

Study Officials

• James CM Ho, MD

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

James CM Ho, MD

CONTACT

852+2255-4349; jhocm@hku.hk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor

Study Record Dates

• First Submitted: March 25, 2025
• First Posted: April 9, 2025
• Study Start: May 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 9, 2025

Record last verified: 2025-04