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COMPLETEDPHASE2

Exploring the Theragnostic Value of Osimertinib in EGFR-mutated Lung Cancer (THEROS)

Exploring the Theragnostic Value of Osimertinib in EGFR-mutated Lung Cancer (THEROS) - A Multicentric Phase II Study in Patients With TKI-resistant EGFR-mutated Lung Cancer Exhibiting Early Metabolic Response to Osimertinib

NCT03810066•University Hospital, Essen

View on ClinicalTrials.gov

Summary

This is a single arm, open label, multicentric proof-of-concept, phase II study in patients with EGFR-mutated non-small-cell lung cancer (NSCLC) with acquired TKI resistance who are "unknown" for EGFR T790M status due to non-informative or unfeasible tumor rebiopsy, and a negative finding for EGFR T790M in a standard plasma genotyping assay. All patients will receive osimertinib as continuous oral treatment for one cycle (28 days). Patients who demonstrate a metabolic response by FDG-PET scanning (to be conducted between day 15 and day 28 of cycle 1) will continue treatment until clinical or radiological progression. Osimertinib treatment will be terminated in patients not experiencing a metabolic response. Primary objective: To study the rate of early metabolic responses to osimertinib in patients with EGFR-mutated NSCLC and acquired TKI resistance who are "unknown" for EGFR T790M status due to non-informative or unfeasible tumor rebiopsy, and a negative finding for EGFR T790M in a standard plasma genotyping assay.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Provision of informed consent prior to any study specific procedures
•2. Patients (male/female) must be \> 18 years of age.
•3. EGFR-mutated NSCLC not amenable to curative treatment (surgery, curative radiochemotherapy).
•4. Acquired resistance to a first- or second-generation EGFR-TKI (e.g. afatinib, erlotinib, gefitinib) following initial benefit (defined as objective response, or stable disease for at least 3 months)
•5. No tumor rebiopsy available or negative result for EGFR T790M mutation status by a SoC molecular pathology test (e.g. Sanger sequencing, PCRbased genotyping, deep sequencing) of a rebiopsy of a progressive tumor lesion
•6. Negative finding from EGFR T790M mutation testing in plasma-derived DNA using a SoC assay (e.g. Roche Cobas)
•7. At least one tumor lesion with significant FDG uptake as determined by PET/CT scanning prior to study treatment
•8. Consent to the research use of donated biological samples.
•9. World Health Organization (WHO) performance status 0-2.
•10. Patients must have a life expectancy ≥ 12 weeks.
+6 more criteria

Exclusion Criteria

•1. EGFR-mutated NSCLC and demonstration of the T790M resistance mutation by standard assay technology in tumor-derived or plasma-derived DNA
•2. Absence of a tumor lesion with significant FDG uptake at PET/CT scanning prior to study treatment
•3. Involvement in the planning and/or conduct of the study (applies to both sponsor staff and/or staff at the study site)
•4. Previous treatment with osimertinib or any experimental or approved mutationspecific EGFR-TKI with clinical activity against the EGFR T790M resistance mutation
•5. Treatment with an investigational drug within one week or five drug half-lives (whichever is longer) of the compound (3 weeks for antibodies)
•6. Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of CYP3A4 (at least 3 week prior) (Appendix A - Guidance regarding Potential Interactions With Concomitant Medications). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4. A list for drug interaction potential is found in section 5.1.6.4 of the osimertinib IB.
•7. Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study Treatment with the exception of alopecia and grade 2, prior chemotherapy related neuropathy.
•8. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
•9. Patients with symptomatic CNS metastases who are neurologically unstable
•10. Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD
+11 more criteria

Locations (1)

Prof. Dr. med. Martin Schuler

Essen, North Rhine-Westphalia, Germany

Key Dates

Start Date

June 3, 2019

Primary Completion Date

December 31, 2021

Completion Date

September 30, 2022

Last Updated

May 9, 2024

Enrollment

ACTUAL participants

Conditions

NSCLCEGFR T790MFDG-PET

Interventions

Osimertinib

DRUG

Sacituzumab Tirumotecan (MK-2870) Versus Pemetrexed and Carboplatin Combination Therapy in Participants With Epidermal Growth Factor (EGFR)-Mutated, Advanced Nonsquamous Non-small Cell Lung Cancer (NSCLC) Who Have Progressed on Prior EGFR Tyrosine Kinase Inhibitors (MK-2870-009)

NCT06305754

Non-small Cell Lung Cancer (NSCLC)

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RECRUITING

Magnetic Resonance Imaging of the Lung: Oncological Applications

NCT07486219

Lung Cancer (NSCLC)

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RECRUITINGPHASE1/PHASE2

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: May 9, 2024Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Exploring the Theragnostic Value of Osimertinib in EGFR-mutated Lung Cancer (THEROS)

Inclusion Criteria

Exclusion Criteria

Sacituzumab Tirumotecan (MK-2870) Versus Pemetrexed and Carboplatin Combination Therapy in Participants With Epidermal Growth Factor (EGFR)-Mutated, Advanced Nonsquamous Non-small Cell Lung Cancer (NSCLC) Who Have Progressed on Prior EGFR Tyrosine Kinase Inhibitors (MK-2870-009)

Magnetic Resonance Imaging of the Lung: Oncological Applications

Study of STK-012 Alone and With Other Treatments in Patients With Advanced Lung Cancer and Other Cancers

Reduced CT + Anti-PD-1 as First Line Tx in Vulnerable Older Adults w/Adv <50% PD-L1 Non-Small Cell Lung Cancer (NSCLC)

The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation (PYNNACLE)

IBI363 vs Docetaxel in Patients With Advanced Squamous Lung Cancer After Standard Treatments Have Failed