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Non-squamous NSCLCPhase 4NCT04413201

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

A Phase 4 study testing Afatinib and Osimertinib in people with Non-squamous NSCLC, run by Michael Hopp at 11 sites in Germany.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-squamous NSCLC
What is being tested?
Afatinib and Osimertinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
11 sitesGermany
Study dates
11 Sep 2020to 31 Dec 2026
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)
  • 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

Who cannot join

  • 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
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  • 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
  • Interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD
  • Any history of or concomitant condition that, in the opinion of the Investigator, would compromise the patient's ability to comply with the study or interfere with the evaluation of the efficacy and safety of the test drug
  • Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of the study drug (e.g. Crohn's disease, ulcerative colitis, chronic diarrhoea, malabsorption)
  • Known active hepatitis B infection (defined as presence of HepB sAg and/ or Hep B DNA), active hepatitis C infection (defined as presence of Hep C RNA) and/or known HIV carrier
  • Previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ or effectively treated malignancy that has been in remission for more than 5 years and is considered to be cured
  • Pregnancy and contraception:
  • Women who are pregnant, nursing, or who plan to become pregnant while in the trial
  • Women of child-bearing potential (WOCBP) and men who are able to father a child, unwilling to be abstinent or use highly effective methods of birth control that result in a low failure rate of less than 1% per year when used consistently and correctly beginning at informed consent, for the duration of study participation and for at least 2 months for females and 4 months for males after last dose
  • Requiring treatment with any of the prohibited concomitant medications protein Inhibitors/Inductors CYP3A4/5 Inhibitors/Inductors that cannot be stopped for the duration of trial participation or concomitant St. John's Wort
  • Uncontrolled brain metastases (Patients with brain or subdural metastases are not eligible, unless they have completed local therapy (≤ 2 weeks apart from last radiotherapy or radiosurgery) and have discontinued the use of corticosteroids, anticonvulsants or have been on stable dose of corticosteroids (i.e. Dexamethasone ≤ 8 mg) for at least 4 weeks before starting study treatment. Any symptoms attributed to brain metastases must be stable for at least 4 weeks before starting study treatment) or Leptomeningeal carcinomatosis 11. Other contraindications to study treatment (Investigators opinion) or legal incapacity or limited legal capacity

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

Germany11 sites

  • Evangelische Lungenklinik Berlin

    Berlin, 13125

  • Klinikum Bremen-Ost

    Bremen, 28325

  • Universitätsklinikum Gießen Marburg

    Giessen, Hesse, 35392

  • Studiengesellschaft Hämato-Onkologie Hamburg

    Hamburg, 20251

  • Evangelisches Krankenhaus Hamm

    Hamm, 59063

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

    Immenstadt im Allgäu, 87509

  • Gemeinnützige Krankenhausbetriebsgesellschaft Konstanz Mbh

    Konstanz, 78464

  • Klinik Löwenstein gGmbH

    Löwenstein, 74245

  • Klinikum der Ludwig-Maximilians-Universität München

    München, Bavaria, 80336

  • Sana-Klinikum Offenbach

    Offenbach, Hesse, 63069

  • Universitätsklinikum Regensburg

    Regensburg, 93053

Other trials in Germany

About this study

Official title: AFAMOSI: Prospective, Randomized, Multicenter Phase IV Study to Evaluate the Efficacy and Safety of Afatinib Followed by Osimertinib Compared to Osimertinib in Patients with EGFRmutated/T790M Mutation Negative Non-squamous NSCLC in the First-line Setting

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.

Being tested
Afatinib, Osimertinib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AfatinibDrug

    Also called Osimertinib

    Afatinib followed by osimertinib or ICT

  • OsimertinibDrug

    Osimertinib followed by ICT

Study groups in NCT04413201
Study groupRoleWhat they receive
AfatinibExperimentalAfatinib followed by osimertinib or ICT depending on T790M status
Receives: Drug: Afatinib; Drug: Osimertinib
OsimertinibActive comparatorOsimertinib followed by ICT
Receives: Drug: Osimertinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 24 months

Secondary outcomes (11)

  1. Time to EGFR-TKI failure (afatinib versus osimertinib)

    Time from randomization until ICT is indicated

    Measured: 24 months

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

    Time from randomization until disease progression according to RECIST or death

    Measured: 24 months

  3. Overall Survival (OS)

    Survival Status

    Measured: 24 months

  4. Response Rate (RR)

    CR+PR according to RECIST

    Measured: 12 months

  5. Response Rate (RR)

    CR+PR according to RECIST

    Measured: 24 months

  6. Disease Control Rate (DCR)

    CR+PR+SD according to RECIST

    Measured: 12 months

  7. Disease Control Rate (DCR)

    CR+PR+SD according to RECIST

    Measured: 24 months

  8. Adverse Events

    Adverse Events as assessed by intensity of the of the adverse events and the causal relation to trial medication Intensity/Severity: investigator will use the following definitions of severity in accordance with National Cancer Institute common terminology criteria for adverse events, CTCAE, version 5.0; assessment of the relationship of an adverse event to the administration of study drug is a clinical decision by the investigator Institute common terminology criteria for adverse events, CTCAE, version 5.0

    Measured: 24 months

  9. Symptom control assessed by patient-reported quality of life (QoL): EQ-5D

    patient-reported quality of life assessed by European Quality of Life 5 Dimensions Questionnaire (EQ-5D)

    Measured: 24 months

  10. Symptom control assessed by patient-reported quality of life (QoL): EORTC QLQ-C30

    patient-reported quality of life assessed by Questionnaire of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)

    Measured: 24 months

  11. Symptom control assessed by patient-reported quality of life (QoL): EORTC QLQ-LC29

    EORTC QLQ-LC29

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jun 2020
  2. Study start11 Sep 2020
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04413201
Sponsor's protocol ID
AFAMOSI
Other IDs
2019-002197-31, 2019
Status last verified
Mar 2025
First submitted
28 May 2020
Last updated
25 Mar 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Afatinib and Osimertinib in people with Non-squamous NSCLC, run by Michael Hopp at 11 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 25 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to EGFR-TKI failure within 24 months for afatinib followed by osimertinib in T790Mpositive group vs osimertinib (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04413201.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2025.

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