AFAMOSI: Efficacy and Safety of Afatinib Followed by Osimertinib Compared to Osimertinib in Patients with EGFRmutated/T790M Mutation Negative Nonsquamous NSCLC

NCT04413201 | Active Not Recruiting Phase 4

• 2 other identifiers: AFAMOSI2019-002197-31
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 11

Brief Summary

This randomized, open label Phase IV trial will be performed in patients with a diagnosis of advanced NSCLC (non-squamous cell histology), harboring EGFR mutation positive but T790M Mutation negative, who have no previous chemotherapy for metastatic NSCLC. Neoadjuvant or adjuvant systemic treatments had to be finished at least (≥) 6 months before study inclusion. In conclusion, this study is investigating the important clinical question whether tumor growth and long term overall survival for a patient is better controlled in a specific treatment sequence of different EGFR-inhibitors. Patients will be treated with registered compounds according to their label in both treatment arms. Thus, all patients will get an effective treatment regimen and patients who progressed on afatinib, and who developed a T790M mutation will be treated subsequently with osimertinib. Those who progressed under osimertinib or under afatinib without T790M mutation will be treated according to the current treatment guidelines with Investigator´s choice of active therapy (ICT) including but not limited to platin doublet chemotherapy.

Conditions

Non-squamous NSCLC

Outcome Measures

Primary Outcomes (1)

• Time to EGFR-TKI failure within 24 months for afatinib followed by osimertinib in T790Mpositive group vs osimertinib

  The main objective is to investigate whether the time to EGFR-TKI failure at 24 months is better for the treatment sequence of afatinib followed by osimertinib in the T790M positive group compared to osimertinib.

  24 months

Secondary Outcomes (11)

• Time to EGFR-TKI failure (afatinib versus osimertinib)

  24 months

• Progression-free survival (PFS: afatinib followed by osimertinib or ICT vs osimertinib followed by ICT)

  24 months

• Overall Survival (OS)

  24 months

• Response Rate (RR)

  12 months

• Response Rate (RR)

  24 months

Study Arms (2)

Afatinib

EXPERIMENTAL

Afatinib followed by osimertinib or ICT depending on T790M status

Drug: Afatinib; Drug: Osimertinib

Osimertinib

ACTIVE COMPARATOR

Osimertinib followed by ICT

Drug: Osimertinib

Interventions

Afatinib DRUG

Afatinib followed by osimertinib or ICT

Also known as: Osimertinib

Afatinib

Osimertinib DRUG

Osimertinib followed by ICT

Afatinib; Osimertinib

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed non-squamous NSCLC harboring EGFR mutation positive but T790M mutation negative by local testing
• Unresectable stage UICC ≥ IIIb or metastatic stage UICC IV disease
• TKI naïve for metastatic NSCLC, neoadjuvant or adjuvant chemotherapy allowed
• At least one evaluable lesion according to RECIST v1.1
• Age ≥ 18 years
• ECOG performance status 0 - 2
• Adequate organ function, defined as all of the following:
• Absolute neutrophil count (ANC) ≥ 1500/mm3. (ANC \> 1000/mm3 may be considered in special circumstances such as benign cyclical neutropenia as judged by the investigator and in discussion with the coordinating investigator)
• Platelet count ≥ 75,000/mm3
• Estimated glomerular filtration rate (eGFR) \> 45 ml/min/1.73 m2 according to the Cockcroft-Gault formula d. If history of cardiac comorbidity: Left ventricular function with resting ejection fraction ≥ 50% or above the institutional lower limit of normal (LLN)
• e. Total Bilirubin ≤ 1.5 times upper limit of normal (ULN), (if related to liver metastases ≤ 3 times ULN). (Patients with Gilbert's syndrome total Bilirubin must be ≤ 4 times institutional upper limit of normal) f. Aspartate amino transferase (AST) or alanine amino transferase (ALT) ≤ 3 times the upper limit of normal (ULN) (if related to liver metastases ≤ 5 times ULN)
• Recovered from any previous therapy related toxicity to ≤ Grade 1 at before randomization (except for stable sensory neuropathy ≤ Grade 2 and alopecia)
• Written informed consen

You may not qualify if:

• Any investigational drug within 30 days or hormonal anticancer treatment within 2 weeks prior to randomization (continued use of anti-androgens and/or gonadorelin analogues for treatment of prostate cancer permitted)
• T790M mutation positive tumors (by local testing)
• Radiotherapy within 2 weeks prior to randomization, except as follows:
• Palliative radiation to target organs other than chest may be allowed up to 1 week prior to randomization
• Single dose palliative treatment for symptomatic metastasis outside above allowance to be discussed with coordinating investigator prior to enrolling
• Major surgery within 2 weeks before starting study treatment or scheduled for surgery during the projected course of the study
• Known hypersensitivity to afatinib or osimertinib or the excipients of any of the trial drugs
• History or presence of clinically relevant cardiovascular abnormalities such as
• uncontrolled hypertension
• congestive heart failure NYHA classification of ≥ 3
• unstable angina or poorly controlled arrhythmia as determined by the investigator
• Myocardial infarction within 6 months prior to randomization
• Clinically important abnormalities in rhythm and conduction as measured by resting electrocardiogram (ECG) (e.g. QTc interval greater than 470 ms) or QTc interval prolongation with signs/symptoms of serious arrhythmia
• Congenital long QT syndrome, congestive heart failure, electrolyte abnormalities, or intake of medicinal products that are known to prolong the QTc interval
• Patients with a past or present medical history of

Sponsors & Collaborators

• Michael Hopp: lead
• Boehringer Ingelheim: collaborator

Study Sites (11)

Klinikum der Ludwig-Maximilians-Universität München

München, Bavaria, 80336, Germany

Location

Universitätsklinikum Gießen Marburg

Giessen, Hesse, 35392, Germany

Location

Sana-Klinikum Offenbach

Offenbach, Hesse, 63069, Germany

Location

Evangelische Lungenklinik Berlin

Berlin, 13125, Germany

Location

Klinikum Bremen-Ost

Bremen, 28325, Germany

Location

Studiengesellschaft Hämato-Onkologie Hamburg

Hamburg, 20251, Germany

Location

Evangelisches Krankenhaus Hamm

Hamm, 59063, Germany

Location

Klinikverbund Allgäug gGmbH, Klinik für Pneumologie, c/o Klinik

Immenstadt im Allgäu, 87509, Germany

Location

Gemeinnützige Krankenhausbetriebsgesellschaft Konstanz Mbh

Konstanz, 78464, Germany

Location

Klinik Löwenstein gGmbH

Löwenstein, 74245, Germany

Location

Universitätsklinikum Regensburg

Regensburg, 93053, Germany

Location

MeSH Terms

Interventions

Afatinib; osimertinib

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Thomas Wehler, Prof Dr med

  Universitätsklinikum Gießen Marburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of Interdisciplinary Center for Clinical Studies (IZKS)

Study Record Dates

• First Submitted: May 28, 2020
• First Posted: June 2, 2020
• Study Start: September 11, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 25, 2025

Record last verified: 2025-03

Locations

DE (11)