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

NCT ID: NCT06918782

Last Updated: 2025-04-09

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-01
• Study Completion Date: 2027-12-31

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

Detailed Description

This is a single-arm clinical trial, subjects will be consented prior to the initiation of osimertinib (as per standard-of-care) with baseline plasma ctDNA EGFR mutations tested in QMH. Those with detectable baseline plasma ctDNA EGFR mutations will undergo a repeat plasma ctDNA test after 3 weeks (+/- 5 days) of osimertinib treatment. The screening period is within 42 days. Enrolled eligible subjects will be started on systemic chemotherapy (pemetrexed and carboplatin or cisplatin) within 6 weeks of starting osimertinib, with the following outcome measures:

Primary outcome: real-world 1-year progression-free survival (rw1yPFS) Secondary outcomes: rw response rate (rwRR), rw PFS (rwPFS), rw overall survival (rwOS), rw time-to-treatment discontinuation (rwTTD), ctDNA clearance rate

Conditions

Lung Cancer (NSCLC)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Combination chemotherapy and osimertinib

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.

Group Type: EXPERIMENTAL

Osimertinib plus platinum doublet chemotherapy

Intervention Type: 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.

Interventions

Osimertinib plus platinum doublet chemotherapy

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Adults above 18 years old, both male and female;

2. Pathologically confirmed lung adenocarcinoma with stage IIIB/C or IV disease (TNM staging version 8);

3. 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;

4. Clinically decided for first-line systemic treatment with osimertinib;

5. Detectable pre-treatment plasma EGFR mutations (by Cobas EGFR Mutation Test v2) and failed clearance 3 weeks (+/- 5 days) after osimertinib treatment;

6. At least one measurable target lesion by RECIST v1.1 criteria;

7. Performance state (ECOG) ≤ 1 and life expectancy ≥ 12 weeks;

8. Females in reproductive age with negative pregnancy test and highly effective means of contraception during and ≥ 4 months after intervention period;

9. Males should agree to have highly effective means of contraception during and ≥ 4 months after intervention period; and

10. Written informed consent obtained.

Exclusion Criteria

1. Mixed NSCLC and small cell carcinoma;

2. Prior systemic anticancer treatment (targeted therapy, chemotherapy or immunotherapy) for metastatic stage NSCLC;

3. Prior adjuvant chemotherapy or targeted therapy within 6 months;

4. Local radiotherapy within 2 weeks or major surgery within 4 weeks;

5. 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);

6. Major medical comorbidities with significant organ dysfunction;

7. Known active hepatitis B or C infection. Chronic hepatitis B on antiviral allowed as per institutional guideline for chemotherapy;

8. Malignancies other than NSCLC; and

9. Known hypersensitivity to pemetrexed or carboplatin.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

James Chung-Man HO

Clinical Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

James CM Ho, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Hong Kong

Central Contacts

James CM Ho, MD

Role: CONTACT

jhocm@hku.hk

852+2255-4349

Other Identifiers

Osim-CT1LEGFR

Identifier Type: -

Identifier Source: org_study_id