NSCLCPhase 2REPOSENCT06315010
Repotrectinib in ROS1-positive Non-small Cell Lung Cancer Patients With Active Brain Metastasis
A Phase 2 study testing Repotrectinib in people with NSCLC and Brain Metastases, run by MedSIR at 17 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NSCLC, Brain Metastases, ROS1 Gene Rearrangement
- What is being tested?
- Repotrectinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 17 sitesin 3 countries
- Study dates
- 27 Jun 2025to Apr 2028
- Phase
- Phase 2
- 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
- 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.
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- 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 may have previously received up to one prior line of anti-ROS1 TKI-based treatment.
- Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan.
- If feasible, archival tumor biopsy sample at baseline (from primary tissue or any metastatic site) should be provided.
- Patient has adequate bone marrow, liver, and renal function:
- Hematological (without platelet, red blood cell transfusion, and/or granulocyte colony-stimulating factor support within 28 days before first study treatment dose): White blood cell (WBC) count > 3.0 x 109/L, absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count ≥ 100.0 x109/L, and hemoglobin ≥ 8.0 g/dL (≥ 4.96 mmol/L).
- Hepatic: Total bilirubin ≤ 1.5 times upper limit of normal (ULN) (≤ 3 in patients with liver metastases or know history of Gilbert's disease); alkaline phosphatase (ALP) ≤ 2.5 times ULN; aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 times ULN (≤ 5 in patients with liver metastases); international normalized ratio (INR) < 1.5.
- Renal: serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 40 mL/min/1.73 m2 based on Cockcroft-Gault glomerular filtration rate estimation for patients with creatinine levels above institutional normal.
- Resolution of all acute toxic effects of prior anti-cancer therapy to grade ≤ 1 as determined by the US National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (v.5.0) (except for alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion).
- Women of childbearing potential (WOCBP) who are sexually active with a non-sterilized male partner must have a negative serum pregnancy test within 14 days before study treatment initiation. In addition, they must agree to use one highly effective method of birth control from the time of screening until 2 months after the last dose of study treatments. Female patients must refrain from egg cell donation and breastfeeding during this same period.
- Note: Due to a potential loss of effectiveness of hormonal contraceptives caused by interaction with study intervention, if WOCBP use hormonal contraceptives (including oral hormonal contraceptives), they must use either another form of non-hormonal highly effective contraception or a reliable barrier method.
- Male participants who are sexually active with a WOCBP partner must be surgically sterile or using an acceptable method of contraception from the time of screening until 4 months after the last administration of the study drug. Male participants must not donate or bank sperm during this same period.
- Patient must be accessible for treatment and follow-up.
Who cannot join
- 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:
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- 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.
- 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).
- 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.
- Presence or history of any other primary malignancy other than NSCLC within 5 years prior to enrollment into the study.
- Note: Patients with a history of adequately treated basal or squamous cell carcinoma of the skin or any adequately treated in situ carcinoma may be included in the study.
- Current use or anticipated need for drugs that are known to be strong Cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or inducers.
- Note: midazolam requires diligent monitoring in situations where there is an unprecedented necessity for co-administration. These cases should be discussed with the study's medical monitor.
- Patients requiring concomitant use of chronic systemic (intravenously [IV] or oral) corticosteroids at doses higher than 8 mg dexamethasone per day or other immunosuppressive medications except for managing adverse events (AEs); (inhaled steroids or intra articular steroid injections are permitted in this study).
- Note: The use of stable corticosteroid therapy in patients with brain metastases should be discussed with the Sponsor's Medical Monitor.
- Hypersensitivity to the Study drug or any of its ingredients.
- Prior exposure to other investigational medical products within five times the half-life of the drug/metabolites before the Screening Visit.
- Contraindications to MRI, including but not limited to claustrophobia.
Trial locations and contacts
17 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
17 sites in 3 countries
Spain14 sites, 14 recruiting
- Recruiting
Hospital General Universitario Dr. Balmis
Alicante
- Recruiting
Hospital de Cruces
Barakaldo
- Recruiting
Hospital Universitari Vall d'Hebron
Barcelona, Barcelona
- Recruiting
UOMI Cancer Center
Barcelona, Barcelona
- Recruiting
Hospital de Vinalopó
Elche, Alicante
- Recruiting
Institut Català d' Oncologia Girona (ICO)
Girona, Girona
- Recruiting
Hospital Universitario de León
León
- Recruiting
Hospital Lucus Agusti
Lugo
- Recruiting
Hospital Beata María Ana
Madrid, Madrid
- Recruiting
Hospital Universitario Vithas Madrid La Milagrosa
Madrid
- Recruiting
Hospital Clínico Universitario Virgen de la Arrixaca
Murcia
- Recruiting
Hospital Universitari Sant Joan de Reus
Reus, Tarragona
- Recruiting
Complejo Hospitalario Universitario de Santiago (CHUS)
Santiago de Compostela
- Recruiting
Hospital Clínico Universitario de Valencia
Valencia
Austria2 sites, 2 recruiting
- Recruiting
Medizinische Universität Graz
Graz
- Recruiting
Medical University of Vienna
Vienna
Germany1 site, 1 recruiting
- Recruiting
Ludwig-Maximilians-University Munich
München
About this study
Official title: A Phase II Study Assessing Safety and Efficacy of Repotrectinib in ROS1-positive Non-small Cell Lung Cancer Patients With Active Brain Metastasis (The REPOSE Study)
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.
Read the detailed description
REPOSE is an international multicenter, open-label, single arm phase II clinical trial designed to evaluate the efficacy of repotrectinib in patients with ROS1-positive NSCLC with BM.
Upon meeting all selection criteria, a total of 20 participants confirmed ROS1 rearrangement will be enrolled. Participants who have received prior chemotherapy, immunotherapy or other non-ROS1 tyrosine kinase inhibitor (TKI) are eligible.
Patients will continue study treatment until end of treatment (EoT) defined as the date of disease progression, death, or discontinuation from the study treatment for any other reason. After study treatment discontinuation, all participants will undergo a safety visit (at 28 ± 7 days after last treatment dose) in order to follow up toxicities and changes in concomitant medication. Patients discontinuing the study treatment at any time will enter a post-treatment follow-up period during which survival and subsequent anticancer therapy information will be collected every 3 months (± 7 days) from the safety visit until death, lost to follow-up, elective withdrawal from the study, or the end of study (EoS), whichever occurs first. Patients who discontinue treatment without evidence of disease progression will be also followed for tumor assessments until documented progression, elective withdrawal from the study, the start of new anti-cancer treatment, or the EoS.
EoS is estimated to occur 13 months after the last participant is included (LPI), unless premature termination of the Study. EoS is defined as the last data collection point in the Study (which can be a clinic visit or a telephone call), unless premature termination of the Study.
The main objective of REPOSE study is to determine the efficacy of repotrectinib at any timepoint during the study period as determined locally by best central nervous system (CNS) response, that is in terms of intracranial objective response rate (IC-ORR).
- Conditions
- NSCLC, Brain Metastases, ROS1 Gene Rearrangement
- Being tested
- Repotrectinib
- Keywords
- Metastatic NSCLC, Brain metastasis, ROS1, Repotrectinib
- Medical subject headings
- Brain Neoplasms, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RepotrectinibDrug
Also called BMS-986472, TPX-0005
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.
| Study group | Role | What they receive |
|---|---|---|
| Repotrectinib | Experimental | Repotrectinib 160 mg orally (PO) every day (QD) for 14 days, and 160 mg twice a day (BID) thereafter. Receives: Drug: Repotrectinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
To assess the efficacy in terms of CBR, defined as the rate of patients with objective response (CR or PR), or stable disease (SD) for IC lesions for at least 24 weeks, as determined locally by the investigator using RANO-BM.
Measured: 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
To assess the efficacy in terms of DCR, defined as the percentage of patients with advanced cancer whose therapeutic intervention has led to a CR, PR, or SD for IC lesions, as determined locally by the investigator using RANO-BM.
Measured: 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
To assess the efficacy in terms of TTR, defined as the period from the treatment initiation to time of the first objective tumor response (tumor shrinkage of ≥ 30%) observed for patients who achieved a CR or PR for IC lesions, as determined locally by the investigator using RANO-BM.
Measured: 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
To assess the efficacy in terms of DoR, defined as the period from the first occurrence of a documented objective response to disease progression or death from any cause, observed for patients who achieved a CR or PR for IC lesions, as determined locally by the investigator using RANO-BM.
Measured: 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)
To assess the efficacy in terms of EC-ORR at any timepoint defined as the rate of patients with partial response (PR) or complete response (CR) for EC and overall lesions, as determined locally by the investigator using Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v.1.1) criteria.
Measured: 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.
CBR for EC and overall lesions
To assess the efficacy in terms of CBR at any timepoint defined as the rate of patients with objective response (CR or PR), or SD for EC and overall lesions, for at least 24 weeks, as determined locally by the investigator using RECIST v.1.1
Measured: 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.
DCR for EC and overall lesions
To assess the efficacy in terms of DCR, defined as the percentage of patients with advanced cancer whose therapeutic intervention has led to a CR, PR, or SD for EC and overall lesions, as determined locally by the investigator using RECIST v.1.1
Measured: 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.
TTR for EC and overall lesions
To assess the efficacy in terms of TTR, defined as the period from the treatment initiation to time of the first objective tumor response (tumor shrinkage of ≥ 30%) observed for patients who achieved a CR or PR for EC and overall lesions, as determined locally by the investigator using RECIST v.1.1
Measured: 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.
DoR for EC and overall lesions
To assess the efficacy in terms of DoR, defined as the period from the first occurrence of a documented objective response to disease progression or death from any cause, observed for patients who achieved a CR or PR for EC and overall lesions, as determined locally by the investigator using RECIST v.1.1.
Measured: 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.
Best percentage of change in tumor burden
To evaluate the best percentage of change in tumor burden determined locally by the investigator using RANO-BM criteria for IC lesions and RECIST v.1.1 for EC and overall lesions.
Measured: 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.
Progression-Free Survival (PFS)
To assess the PFS, defined as the period from treatment initiation to the first occurrence of disease progression or death from any cause, whichever occurs first, determined locally per RANO-BM criteria for IC lesions and RECIST criteria v.1.1 for EC and overall lesions.
Measured: 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.
Overall Survival (OS)
To determine the OS, defined as the period from treatment initiation to death from any cause, determined locally by the investigator.
Measured: 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.
Neurologic function
To assess the patient neurologic function with the Neurologic Assessment in Neuro-Oncology (NANO) scale
Measured: 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.
Quality of life (QoL) with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-30)
To evaluate changes from baseline and during repotrectinib treatment in terms of patient-reported outcome (PRO) assessments of QoL and treatment-related symptoms as measured by EORTC QLQ-C30 scale.
EORTC QLQ-C30 scale aims to measure cancer patients' physical, psychological and social functions. Scale and single items are transformed into scores ranging from 0 to 100. A high score for a functional scale represents a high level of functioning, whereas a high score for a symptom scale/single item represents a high level of symptomatology.
Measured: 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.
QoL with the brain cancer specific questionnaire (QLQ-C20).
To evaluate changes during repotrectinib treatment in terms of PRO assessments of QoL and treatment-related symptoms as measured by EORTC QLQ-C20 scale.
EORTC QLQ-BN20 brain specific tool aims to measure the effects of brain tumors and its treatment on symptoms, functions and health-related quality of life.
Scale and single items are transformed into scores ranging from 0 to 100. A high score for a functional scale represents a high level of functioning, whereas a high score for a symptom scale/single item represents a high level of symptomatology.
Measured: 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.
Safety and tolerability
To evaluate the safety and toxicity profile of treatment with of repotrectinib as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
Measured: Through study completion, an average of 13 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2024
- Study start27 Jun 2025
- Primary completionMar 2027 (estimated)
- Study completionApr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NSCLCStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- MedSIR
- Sponsor type
- University, hospital or other
- Collaborators
- Medical University of Vienna
- Responsible party
- Sponsor
- Investigators
- Thorsten Füreder, MD, Principal investigator, Medical University of Vienna, Vienna General Hospital (Austria)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06315010
- Sponsor's protocol ID
- MedOPP662
- Other IDs
- 2023-508112-35-00, CA127-1061, 2023
- Acronym
- REPOSE
- Status last verified
- Sep 2026
- First submitted
- 16 Feb 2024
- Last updated
- 9 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study Assessing Safety and Efficacy of Repotrectinib in ROS1-positive Non-small Cell Lung Cancer Patients With Active Brain Metastasis (The REPOSE Study)
- ClinicalTrials.gov ID
- NCT06315010
- Acronym / sponsor ID
- REPOSE / MedOPP662
- Conditions
- NSCLC, Brain Metastases, ROS1 Gene Rearrangement
- Keywords
- Metastatic NSCLC, Brain metastasis, ROS1, Repotrectinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- MedSIRUniversity, hospital or other
- Collaborators
- Medical University of Vienna
- Study start
- 27 Jun 2025 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Apr 2028 (estimated)
- First posted
- 18 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
REPOSE is an international multicenter, open-label, single arm phase II clinical trial designed to evaluate the efficacy of repotrectinib in patients with ROS1-positive NSCLC with BM.
Upon meeting all selection criteria, a total of 20 participants confirmed ROS1 rearrangement will be enrolled. Participants who have received prior chemotherapy, immunotherapy or other non-ROS1 tyrosine kinase inhibitor (TKI) are eligible.
Patients will continue study treatment until end of treatment (EoT) defined as the date of disease progression, death, or discontinuation from the study treatment for any other reason. After study treatment discontinuation, all participants will undergo a safety visit (at 28 ± 7 days after last treatment dose) in order to follow up toxicities and changes in concomitant medication. Patients discontinuing the study treatment at any time will enter a post-treatment follow-up period during which survival and subsequent anticancer therapy information will be collected every 3 months (± 7 days) from the safety visit until death, lost to follow-up, elective withdrawal from the study, or the end of study (EoS), whichever occurs first. Patients who discontinue treatment without evidence of disease progression will be also followed for tumor assessments until documented progression, elective withdrawal from the study, the start of new anti-cancer treatment, or the EoS.
EoS is estimated to occur 13 months after the last participant is included (LPI), unless premature termination of the Study. EoS is defined as the last data collection point in the Study (which can be a clinic visit or a telephone call), unless premature termination of the Study.
The main objective of REPOSE study is to determine the efficacy of repotrectinib at any timepoint during the study period as determined locally by best central nervous system (CNS) response, that is in terms of intracranial objective response rate (IC-ORR).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Repotrectinib | Experimental | Drug: RepotrectinibRepotrectinib 160 mg orally (PO) every day (QD) for 14 days, and 160 mg twice a day (BID) thereafter. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- 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.
Key exclusion criteria (24 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RepotrectinibAlso: BMS-986472, TPX-0005Repotrectinib 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. | Drug | Repotrectinib |
Primary outcome
Intracranial Objective Response Rate (IC-ORR)
Time frame: 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.
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.
16 secondary outcomes
Clinical Benefit Rate (CBR) for intracranial (IC) lesions
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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.
CBR for EC and overall lesions
Time frame: 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.
DCR for EC and overall lesions
Time frame: 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.
TTR for EC and overall lesions
Time frame: 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.
DoR for EC and overall lesions
Time frame: 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.
Best percentage of change in tumor burden
Time frame: 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.
Progression-Free Survival (PFS)
Time frame: 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.
Overall Survival (OS)
Time frame: 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.
Neurologic function
Time frame: 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.
Quality of life (QoL) with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-30)
Time frame: 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.
QoL with the brain cancer specific questionnaire (QLQ-C20).
Time frame: 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.
Safety and tolerability
Time frame: Through study completion, an average of 13 months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Thorsten Füreder, MD principal investigator
Medical University of Vienna, Vienna General Hospital (Austria)
17 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Repotrectinib in people with NSCLC and Brain Metastases, run by MedSIR at 17 sites in 3 countries.
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 26 inclusion and 24 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: looking for participants now, as of the sponsor's last update on 9 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Spain, Austria, 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Contact MEDSIR (+34 93 2214135, contact.trials@medsir.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intracranial Objective Response Rate (IC-ORR) (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Sep 2026.