Combining Afatinib and Concurrent Chemotherapy, Followed by Osimertinib and Concurrent Chemotherapy, in Untreated EGFR Positive NSCLC Tumors

NCT05298176 | Completed Phase 2 DMC

• 2 other identifiers: NL74383.029.202020-003025-37
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the COMBINATION trial is to prospectively study the sequential approach of using afatinib combined with a short course of chemotherapy, followed by osimertinib, upon progression and acquisition of a T790M mutation, also combined with a short course of chemotherapy.

Conditions

Non-Small Cell Lung Cancer

Keywords

EGFR; EGFR mutation; Afatinib; Osimertinib; Chemotherapy; Combination strategy

Outcome Measures

Primary Outcomes (1)

• Disease control rate (DCR)

  To assess the efficacy of the sequential strategy of front-line afatinib-chemo, followed by a treatment with osimertinib-chemo in those patients that develop a T790M mutation as a mechanism of resistance

  18 months

Secondary Outcomes (7)

• Progression Free Survival (PFS)

  From start of therapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 50 months

• Overall Survival (OS)

  From start of therapy until the date of death from any cause, assessed up to 50 months

• Objective response rate according to RECIST v1.1 after start of afatinib

  At 6 weeks

• Objective response rate according to RECIST v1.1 after start of afatinib

  At 12 weeks

• Objective response rate according to RECIST v1.1 after start of osimertinib

  At 6 weeks

Study Arms (1)

Patients with untreated EGFR positive NSCLC tumors

EXPERIMENTAL

TKI-naïve advanced NSCLC patients, harboring a non-exon20insertion uncommon EGFR mutation, who are eligible for treatment with afatinib in 1st line

Drug: Afatinib, Osimertinib, Carboplatin and Pemetrexed

Interventions

Afatinib, Osimertinib, Carboplatin and Pemetrexed DRUG

This study consists of 2 parts. Part 1 is defined as a first line treatment with afatinib orally (30 mg once a day) for the first 6 weeks, followed by concurrent use of afatinib (20mg once a day, part 1B) plus 2 cycles of carboplatin and pemetrexed (21 days per cycle); followed by afatinib monotherapy (30mg once a day). Part 2 comprises a 2nd line treatment with osimertinib (80 mg once daily) after failure of part 1, only in T790M positive patients for the first 6 weeks, followed by concurrent use of osimertinib (80mg once a day) plus 2 cycles of carboplatin and pemetrexed (21 days per cycle); followed by osimertinib monotherapy (80mg once a day).

Patients with untreated EGFR positive NSCLC tumors

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed NSCLC, positive for non-exon20insertion uncommon EGFR mutations that are eligible for afatinib therapy in first line
• WHO PS 0-2
• Be willing and able to provide written informed consent for the trial.
• Be above 18 years of age on day of signing informed consent.
• Patients must have radiological measurable disease
• Demonstrate adequate organ function, as deemed acceptable by the treating physician in the context of metastatic NSCLC.

You may not qualify if:

• Inability to provide informed consent
• Inability to take study medications
• Patients with symptomatic or unstable CNS metastases
• Prior EGFR TKI or platinum-doublet therapy for advanced stage NSCLC. Prior (neo)adjuvant treatments are allowed when the last administration is one year or more.
• Evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Active infection requiring systemic therapy.
• Active Hepatitis B or C.
• Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Patient is pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial, starting with the screening visit.

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Study Sites (1)

Amsterdam UMC, location VUmc

Amsterdam, North Holland, 1081 HV, Netherlands

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Afatinib; osimertinib; Carboplatin; Pemetrexed

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)

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

Study Officials

• Idris Bahce, MD, PhD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

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: Principal Investigator

Study Record Dates

• First Submitted: January 15, 2022
• First Posted: March 28, 2022
• Study Start: January 4, 2022
• Primary Completion: April 1, 2024
• Study Completion: April 1, 2024
• Last Updated: March 28, 2025

Record last verified: 2025-03

Locations

NL (1)