REPotrectinib in ROS1-positive Non-small Cell Lung Cancer Patients With Active Brain mEtastasis

NCT06315010 | Recruiting Phase 2 DMC

• 3 other identifiers: MedOPP6622023-508112-35-00CA127-1061
• Study Type: interventional
• Target: 20
• Locations: 3 countries
• Sites: 16

Brief Summary

REPOSE is a phase II clinical trial exploring the safety and efficacy of repotrectinib in patients with non-small cell lung cancer (NSCLC) characterized by the presence of brain metastasis (BM) and whose tumors have mutated ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) gene.

Conditions

NSCLC; Brain Metastases; ROS1 Gene Rearrangement

Keywords

Metastatic NSCLC; Brain metastasis; ROS1; Repotrectinib

Outcome Measures

Primary Outcomes (1)

• Intracranial Objective Response Rate (IC-ORR)

  To assess the efficacy in terms of IC-ORR at any timepoint defined as the rate of patients with partial response (PR) or complete response (CR) for IC lesions, as determined locally by the investigator as judged by best CNS response according to the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria.

  From date of inclusion until the date of first documented progression or date of death from any cause or treatment discontinuation from any other reason, whichever came first, assessed through study completion, an average of 13 months.

Secondary Outcomes (16)

• Clinical Benefit Rate (CBR) for intracranial (IC) lesions

  From date of inclusion until the date of first documented progression or date of death from any cause or treatment discontinuation from any other reason, whichever came first, assessed through study completion, an average of 13 months.

• Disease Control Rate (DCR) for IC lesions

  From date of inclusion until the date of first documented progression or date of death from any cause or treatment discontinuation from any other reason, whichever came first, assessed through study completion, an average of 13 months.

• Time to Response (TTR) for IC lesions

  From date of inclusion until the date of first documented progression or date of death from any cause or treatment discontinuation from any other reason, whichever came first, assessed through study completion, an average of 13 months.

• Duration of Response (DoR) for IC lesions

  From date of inclusion until the date of first documented progression or date of death from any cause or treatment discontinuation from any other reason, whichever came first, assessed through study completion, an average of 13 months.

• Objective Response Rate for extracranial (EC) and overall lesions (EC-ORR)

  From date of inclusion until the date of first documented progression or date of death from any cause or treatment discontinuation from any other reason, whichever came first, assessed through study completion, an average of 13 months.

Other Outcomes (3)

• Exploratory endpoint: Genetic studies using blood samples to investigate the potential association with clinical outcomes

  Through study completion, an average of 13 months.

• Exploratory endpoint: ROS1 gene expression analysis using baseline tissue samples to investigate the potential association with clinical outcomes

  Through study completion, an average of 13 months.

• Exploratory endpoint: Analysis of medical imaging to identify potential biomarkers associated with clinical outcomes

  Through study completion, an average of 13 months.

Study Arms (1)

Repotrectinib

EXPERIMENTAL

Repotrectinib 160 mg orally (PO) every day (QD) for 14 days, and 160 mg twice a day (BID) thereafter.

Drug: Repotrectinib

Interventions

Repotrectinib DRUG

Repotrectinib is administered orally in capsule form, with each capsule containing size 0 hard gelatin 40 mg of the active compound in bottles containing 30 capsules. Repotrectinib is administered orally in the form of capsules. The capsules are taken by mouth and swallowed intact (without chewing, crushing, or opening) with water or another suitable liquid.

Also known as: BMS-986472, TPX-0005

Repotrectinib

Eligibility Criteria

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

You may qualify if:

• Patients will be included in the study only if they meet all the following criteria:
• Patient must be capable to understand the purpose of the study and have signed written informed consent form (ICF) prior to beginning specific protocol procedures.
• Female or male patients ≥ 18 years of age at the time of signing ICF.
• Patients must be capable to swallow capsules intact (without chewing, crushing, or opening).
• Histologically documented NSCLC.
• Patients may have active brain metastases with or without related symptoms.
• No indication for immediate local therapy (neurosurgery, brain radiotherapy) of brain metastases per local investigator.
• Note: in case of immediate local therapy is needed, the study's medical monitor should be consulted.
• Type II leptomeningeal disease per European Association of Neuro-Oncology (EANO) - European Society for Medical Oncology (ESMO) Clinical Practice Guidelines are allowed.
• Patients with confirmed ROS1 rearrangement. Prior to study enrollment, patients must have had confirmation of ROS1 rearrangement, which should have been determined locally by a certified laboratory using methods such as fluorescent in situ hybridization (FISH), next generation sequencing (NGS), quantitative PCR (qPCR), or immunohistochemistry (IHC).
• Measurable disease according to RANO-BM criteria, with at least one measurable brain lesion of ≥10 mm on T1-weighted, gadolinium-enhanced magnetic resonance imaging (MRI).
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• Minimum life expectancy of ≥ 6 weeks at screening.
• No limit in number of prior chemotherapies, immunotherapy or other non-ROS1 TKI regimens. De novo patients can also be included.
• Patients must not have previously received any ROS1 TKI-based treatment.

You may not qualify if:

• Any patient meeting ANY of the following criteria will be excluded from the study:
• Major surgery within four weeks of the start of treatment.
• Type I leptomeningeal disease per ESMO-EANO guidelines.
• Have received prior radiotherapy within two weeks before the first dose of Study treatment (four weeks in case of radiation therapy of the central nervous system). Participants must have recovered from all radiation-related toxicities, not require steroids, and not have had radiation pneumonitis.
• Treatment with approved or investigational cancer therapy within14 days prior to initiation of Study treatment.
• Any of the following cardiac criteria:
• I. Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) \> 470 msec obtained from 3 ECGs, using the screening clinic ECG machine-derived QTc value.
• II. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval \> 250 msec).
• III. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval.
• Clinically significant cardiovascular disease (either active or within 6 months prior to enrollment): myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association Classification Class ≥ II), cerebrovascular accident or transient ischemic attack, symptomatic bradycardia, requirement for anti-arrhythmic medication. Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥ 2.
• Known clinically significant active infections not controlled with systemic treatment (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact on drug absorption.
• Peripheral neuropathy grade ≥ 2.
• History of extensive, disseminated, bilateral, or presence of NCI CTCAE grade 3 or 4 interstitial fibrosis or interstitial lung disease (ILD) including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, ILD, obliterative bronchiolitis, and pulmonary fibrosis. Patients with a history of prior radiation pneumonitis are not excluded.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or that may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study or could compromise the protocol objectives in the opinion of the Investigator.

Sponsors & Collaborators

• MedSIR: lead
• Medical University of Vienna: collaborator

Study Sites (16)

Medizinische Universität Graz

Graz, 8010, Austria

RECRUITING

Medical University of Vienna

Vienna, Austria

RECRUITING

Ludwig-Maximilians-University Munich

München, Germany

RECRUITING

Hospital de Vinalopó

Elche, Alicante, 03293, Spain

RECRUITING

Hospital Universitari Sant Joan de Reus

Reus, Tarragona, 43204, Spain

RECRUITING

Hospital General Universitario Dr. Balmis

Alicante, 03010, Spain

RECRUITING

Hospital de Cruces

Barakaldo, 48903, Spain

RECRUITING

UOMI Cancer Center

Barcelona, 08017, Spain

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Institut Català d' Oncologia Girona (ICO)

Girona, 17007, Spain

RECRUITING

Hospital Universitario de León

León, 24008, Spain

RECRUITING

Hospital Lucus Agusti

Lugo, 27003, Spain

RECRUITING

Hospital Beata María Ana

Madrid, 28007, Spain

RECRUITING

Hospital Universitario Vithas Madrid La Milagrosa

Madrid, 28010, Spain

RECRUITING

Complejo Hospitalario Universitario de Santiago (CHUS)

Santiago de Compostela, 15706, Spain

RECRUITING

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

RECRUITING

MeSH Terms

Conditions

Brain Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

repotrectinib

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Matthias Preusser, md

  Medical University of Vienna, Vienna General Hospital (Austria)

  PRINCIPAL INVESTIGATOR

• Barbara Kiesewetter, MD

  Medical University of Vienna, Vienna General Hospital (Austria)

  PRINCIPAL INVESTIGATOR

• Thorsten Füreder, MD

  Medical University of Vienna, Vienna General Hospital (Austria)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

MEDSIR

CONTACT

+34 93 2214135; contact.trials@medsir.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2024
• First Posted: March 18, 2024
• Study Start: June 27, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: February 25, 2026

Record last verified: 2025-06

Locations

ES (13); DE (1); AU (2)