NSCLC Stage IVPhase 2REPOROSNCT06552234
Phase II Efficacy Study of Repotrectinib in Frail and/or Elderly Patients With ROS1-rearranged Advanced NSCLC
A Phase 2 study testing Repotrectinib in people with NSCLC Stage IV and NSCLC, Stage III, run by Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer at 20 sites in France.
Trial summary
ROS1 rearrangements are rare, accounting for only 1-2% of NSCLC cases, but have been associated with response to ROS1 inhibitors, such as crizotinib and entrectinib. However, many patients develop resistance to the tyrosine-kinase inhibitors (TKIs), creating a need for new treatments. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NSCLC Stage IV, NSCLC, Stage III
- What is being tested?
- Repotrectinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 20 sitesFrance
- Study dates
- 1 Oct 2024to Sep 2031
- 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
- Eligible patients are defined as patients with
- Eastern Cooperative Oncology Group (ECOG) PS ≥ 2 at the time of inclusion and/or
- Age ≥ 70 years
- Age ≥ 18 years
- Histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC harboring an ROS1 gene rearrangement as by any nucleic acid-based diagnostic testing method (e.g., next-generation sequencing [NGS], Sanger sequencing, reverse transcription-polymerase chain reaction), Break-apart fluorescence in situ hybridization (FISH) or Immunohistochemistry (IHC) (confirmed by NGS or qPCR test).
- Willing and able to provide written institutional review board (IRB)/institutional ethics committee-approved Informed Consent.
Show all 38Show fewer
- At least 1 measurable target lesion according to RECIST (v1.1). CNS-only measurable disease as defined by RECIST (v1.1) is allowed.
- Prior cytotoxic chemotherapy for advanced or metastatic disease is allowed. At the time of starting treatment with repotrectinib, at least 14 days or 5 half-lives (whichever is shorter) must have elapsed after discontinuation of prior cytotoxic chemotherapy (or at least 42 days for prior nitrosoureas, mitomycin C, and liposomal doxorubicin) and all side effects from prior treatments must have resolved to grade ≤ _1 (CTCAE Version 5.0 with the exception of alopecia.
- Prior immunotherapy (e.g., anti-PD-1, anti-PDL1, anti-TIM3, anti-OX40) is allowed. At the time of starting treatment with repotrectinib, at least 14 days must have elapsed after discontinuation of prior immunotherapy treatment and all immune-related side effects from prior treatments must have resolved to grade ≤ _1.
- No prior ROS1 TKI is allowed for the TKI naïve cohort.
- Prior ROS1 TKI is allowed for the TKI pretreated cohort (max 30% of patients). At least 7 days or 5 half-lives (whichever is shorter) must have elapsed since completion of treatment with the last ROS1i prior to starting treatment with repotrectinib for subjects enrolling into the TKI-pretreated expansion cohorts. All side effects from prior treatments with ROS1i must have resolved to grade ≤ _1 prior to starting treatment with repotrectinib.
- Prior ROS1i allowed include crizotinib, ceritinib, lorlatinib, brigatinib, entrectinib, ensartinib, cabozantinib.
- Subjects with symptomatic CNS metastases and/or asymptomatic leptomeningeal carcinomatosis are eligible.
- Life expectancy ≥3 months
- Subject affiliated to an appropriate social security system
- Adequate hematologic and end-organ function, defined by the following laboratory
- ANC ≥ 1500 /mm3 without granulocyte colony-stimulating factor support
- Lymphocyte count ≥ 500/mm3
- Platelet count ≥ 100,000/mm3 without transfusion
- Hemoglobin ≥ 9.0 g/dL. Patients may be transfused to meet this criterion.
- INR or aPTT ≤ 1.5, upper limit of normal (ULN)
- This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be receiving a stable dose.
- ASAT, ALAT, and alkaline phosphatase ≤ 2.5xULN, with the following exceptions:
- Patients with documented liver metastases: ASAT and/or ALAT ≤ 5xULN
- Patients with documented liver or bone metastases: alkaline phosphatase < 5xULN
- Serum bilirubin ≤1.25xULN
- Patients with known Gilbert disease who have serum bilirubin level ≤ 3xULN may be enrolled.
- Calculated creatinine clearance (CRCL) ≥ 45 mL/min
- Adequate method of contraception during the treatment period
- For Females:
- All women of childbearing potential (WOCBP) must agree to avoid pregnancy during the study and must use a highly effective method of contraception during study treatment with repotrectinib and for at least 2 months following the final dose.
- Highly effective contraceptive methods consist of prior sterilization, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), injectable or implantable contraceptives and abstinence.
- Hormonal contraception must begin 7 days prior to the first dose of study treatment.
- 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.
- Female subjects must refrain from egg donation from screening through at least 2 months after the last dose of study drug.
- For Males:
- Male participants with WOCBP partners must use latex condoms during treatment with repotrectinib and for 4 months following the final dose even if the participant has undergone a successful vasectomy or if the partner is pregnant or breastfeeding.
- Male subjects must refrain from sperm donation from screening through at least 4 months after the last dose of study drug
Who cannot join
- Malignancies other than NSCLC within 2 years prior to inclusion, with the exception of those with a negligible risk of metastasis or death (e.g., expected 5-year OS ≥ 90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous-cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent)
- Patients with active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and absence of HBsAg) are eligible only if they are negative for HBV DNA. Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA.
- Active tuberculosis
- Severe infections within 2 weeks prior to inclusion, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
- Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction, or cerebrovascular accident within 3 months prior to inclusion, unstable arrhythmias, or unstable angina
- Major surgical procedure other than for diagnosis within 28 days prior to inclusion or anticipation of need for a major surgical procedure during the course of the study
Show all 11Show fewer
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications.
- Patients with illnesses or conditions that interfere with their capacity to understand follow and/or comply with study procedures.
- Concurrent participation in any therapeutic clinical trial
- Patient deprived of liberty or placed under the authority of a tutor or a curator
- Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol
Trial locations and contacts
20 sites in 1 country. Contact the study team or a site near you to ask about taking part.
20 sites in 1 country
France20 sites, 20 recruiting
- Recruiting
CH Aix-en-Provence
Aix-en-Provence, Bouches Du Rhône
Stéphanie MARTINEZ, smartinez@ch-aix.fr
- Recruiting
CHU Angers
Angers
Grégoire JUSTEAU, gregoire.justeau@chu-angers.fr
- Recruiting
CHU Bordeaux
Bordeaux
Claire BARDEL, claire.bardel@chu-bordeaux.fr
- Recruiting
CHU Brest
Brest
Margaux GEIER, margaux.geier@chu-brest.fr
- Recruiting
Centre François Baclesse
Caen
Pierre DEMONTROND, p.demontrond@baclesse.unicancer.fr
- Recruiting
CH Chambéry
Chambéry
Julian PINSOLLE, julian.pinsolle@ch-metropole-savoie.fr
- Recruiting
Hôpitaux civils de Colmar
Colmar
Lionel MOREAU, lionel.moreau@ch-colmar.fr
- Recruiting
CHI Créteil
Créteil
Gaëlle ROUSSEAU BUSSAC, gaelle.rousseaubussac@chicreteil.fr
- Recruiting
CHD Vendée
La Roche-sur-Yon
Acya BIZIEUX, acya.bizieux@ght85.fr
- Recruiting
CHRU Lille
Lille
Alexis CORTOT, alexis.cortot@chu-lille.fr
- Recruiting
CHU Limoges
Limoges
Yannick SIMONNEAU, MD, 05 55 05 55 55, Yannick.simonneau@chu-limoges.fr
- Recruiting
Hospices Civils de Lyon
Lyon
Thomas PIERRET, thomas.pierret@chu-lyon.fr
- Recruiting
AP-HM
Marseille, Bouches Du Rhône
Laurent GREILLIER, laurent.greillier@ap-hm.fr
- Recruiting
CH Cornouaille
Quimper
Maël DOMBLIDES, mael.domblides@ch-cornouaille.fr
- Recruiting
CHU Rennes
Rennes
Yannick LE GUEN, yannick.le.guen@chu-rennes.fr
- Recruiting
CHU Rouen
Rouen
Florian GUISIER, florian.guisier@chu-rouen.fr
- Recruiting
Hôpital Foch
Suresnes
Hélène DOUBRE, h.doubre@hopital-foch.com
- Recruiting
HIA Sainte Anne
Toulon, Var
Olivier BYLICKI, bylicki.olivier@yahoo.fr
- Recruiting
CHU Toulouse
Toulouse
Laurence BIGAY-GAME, bigaygame.l@chu-toulouse.fr
- Recruiting
Hôpitaux Nord-Ouest
Villefranche-sur-Saône
Lionel FALCHERO, lfalchero@hno.fr
About this study
Official title: Open-label Phase II Efficacy Study of Repotrectinib in Frail (PS ≥2) and/or Elderly Patients With ROS1-rearranged Advanced NSCLC
ROS1 rearrangements are rare, accounting for only 1-2% of NSCLC cases, but have been associated with response to ROS1 inhibitors, such as crizotinib and entrectinib. However, many patients develop resistance to the tyrosine-kinase inhibitors (TKIs), creating a need for new treatments.
Repotrectinib is a new-generation TKI designed against ROS1 or NTRK rearranged malignancies (Drilon 2018). Early phase clinical data support activity of repotrectinib in patients with NSCLC harboring such gene rearrangements (TRIDENT-1 study), but there are limited evidence in frail populations, such as poor performance status patients and/or elderly patients, who are classically excluded from clinical trials or underrepresented.
The present study aims to assess the activity and tolerability of repotrectinib in frail (PS ≥2) and/or elderly patients with ROS1-rearranged advanced NSCLC.
Read the detailed description
This is a national, multicenter, phase II, prospective, open label, non-randomized, interventional study.
Frail (PS≥2) and/or elderly patients (≥70 years) with histologically/cytologically proven stage IV or stage III non-eligible to local treatment NSCLC harboring an ROS1 gene rearrangement treated by Repotrectinib (160 mg twice a day (BID), until progression or unacceptable toxicity) in first or any line.
- Conditions
- NSCLC Stage IV, NSCLC, Stage III
- Being tested
- Repotrectinib
- Keywords
- tyrosine-kinase inhibitors, Frail patients, Elderly patients, ROS1 rearrangements, resistance
- Medical subject headings
- 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
Repotrectinib 160 mg BID, until progression or unacceptable toxicity
| Study group | Role | What they receive |
|---|---|---|
| Repotrectinib treatment | Experimental | patient treated by Repotrectinib until progression or unacceptable toxicity Receives: Drug: Repotrectinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR) according to RECIST v1.1.
ORR defined as the proportion of patients who achieved a complete or partial response according to RECIST v1.1 from the date of first treatment administration until disease progression or death if patient died before progression or the introduction of a new treatment assessed by blinded independent central review.
Tumor assessments will be performed at Screening, every 2 Months during the first year then every 3 months thereafter until documented progression, death or the introduction of a new treatment.
Patients who discontinue treatment for reasons other than radiographic disease progression per RECIST v1.1 (toxicity, symptomatic deterioration) will continue scheduled tumor assessments until radiographic disease progression per RECIST v1.1, withdrawal of consent, death, or study termination by the co-Sponsors, whichever occurs first
Measured: From the date of first treatment administration until the date of disease progression or death if patient died before progression) or the introduction of a new treatment, which ever occurs earlier, assessed up to 7 years
Secondary outcomes (16)
Progression free survival (PFS) by masked, independent central review
Independent central review of progression free survival (PFS) from Repotrectinib initiation, defined as the time from first dose of Repotrectinib to first documentation of objective disease progression (RECIST v1.1) or to death from any cause. Patients lost to follow-up will be censored as the last date of radiological assessment without progression.
Tumor assessments will be performed at Screening, every 2 Months during the first year then every 3 months thereafter until documented progression, death or the introduction of a new treatment.
Patients who discontinue treatment for reasons other than radiographic disease progression per RECIST v1.1 (e.g., toxicity, symptomatic deterioration) will continue scheduled tumor assessments until radiographic disease progression per RECIST v1.1, withdrawal of consent, death, or study termination by the co-Sponsors, whichever occurs first.
Measured: From the date of first treatment administration until the date of disease progression (or death if patient died before progression), which ever occurs earlier, assessed up to 7 years
Disease control rate (DCR) by masked, independent central review
DCR, defined as the proportion of patients who achieved a complete response (CR) or partial response (PR) or stable disease (SD) according to RECIST v1.1 assessed by BICR.
Tumor assessments will be performed at Screening, every 2 Months during the first year then every 3 months thereafter until documented progression, death or the introduction of a new treatment.
Patients who discontinue treatment for reasons other than radiographic disease progression per RECIST v1.1 (e.g., toxicity, symptomatic deterioration) will continue scheduled tumor assessments until radiographic disease progression per RECIST v1.1, withdrawal of consent, death, or study termination by the co-Sponsors, whichever occurs first.
Measured: From the date of first treatment administration until the date of disease progression (or death if patient died before progression), which ever occurs earlier, assessed up to 7 years
Intracranial ORR (ic-ORR) by masked, independent central review
ic-ORR, defined as the proportion of patients who achieved CR or PR in measurable brain metastases based on RECIST 1.1 criteria
Measured: From the date of first treatment administration until the date of disease progression (or death if patient died before progression), which ever occurs earlier, assessed up to 7 years
Overall survival (OS)
OS, defined as the time from first dose of Repotrectinib until death from any cause. Patients lost to follow-up will be censored at the last date known to be alive.
OS will be evaluated every 3 months (until death or lost to follow-up) in patients who:
- Discontinue the study treatment due to disease progression
- Discontinue the study treatment due to an unacceptable toxicity or any other reason, and who start a new therapy
- Reach the End-of-study Time Point.
Measured: From the date of first treatment administration until the date of death from any cause, assessed up to 7 years
Toxicities occurring during either the induction or maintenance treatment in terms of kind, grade, time of onset, reversibility, according to NCI-CTCAE v5.0 criteria
Proportion (%) of patients with any adverse event (AE) and number of events for all AEs, all serious AEs (SAEs) and all AEs of grade ≥3 according to the National Cancer Institute (NCI) Common terminology criteria for adverse events (CTCAE) v5.0 criteria.
Measured: From the date of first treatment administration up to 30 days after the last dose of study treatment
Duration of response (DOR) assessed in patients who had an objective response as determined by the investigator using RECIST v1.1
DOR, defined as the time from the first documented objective response (CR or PR) until disease progression or death, whichever occurs first.
Measured: From the date of first documented objective response (CR or PR) until disease progression or death, which ever occurs earlier, assessed up to 7 years
Time to deterioration in lung-related symptoms
Time to deterioration in lung-related symptoms, defined as the time from inclusion to the time the patient's score on the EORTC QLQ C30 or QLQ-LC13 shows a ≥10-point increase above baseline in each of the following EORTC-transformed scores for cough, dyspnea (single item), dyspnea (multi-item subscale) and chest pain. Patients lost to follow-up without previous QOL deterioration will be censored at the last EORTC assessment date.
QoL/PRO questionnaires may be filled out up until D1 every 8 weeks ±7 days during the first year, then every 12 weeks ±7 days thereafter at Progression.
Measured: From the date of inclusion to the date the patient's score on the EORTC QLQ C30 or QLQ-LC13 shows a ≥10-point increase above baseline, assessed up to 7 years
Time to deterioration in quality of life
Time to deterioration in quality of life, defined as the time from inclusion to the time the patient's score on the EQ-5D-3L utility score shows a 0.08 point decrease above baseline. Patients lost to follow-up without previous EQ-5D-3L deterioration will be censored at the last EQ-5D-3L assessment.
QoL/PRO questionnaires may be filled out up until D1 every 8 weeks ±7 days during the first year, then every 12 weeks ±7 days thereafter at Progression.
Measured: From the date of inclusion to the date the patient's score on the EQ-5D-3L utility score shows a 0.08 point decrease above baseline, assessed up to 7 years
PFS subgroup analysis according to Performance Status and age
PFS according to different subgroups :
- PS ≥ 2 at the time of inclusion
- Age ≥ 70 years
Measured: From the date of first treatment administration until the date of disease progression (or death if patient died before progression), which ever occurs earlier, assessed up to 7 years
OS subgroup analysis according to Performance Status and age
OS according to different subgroups :
- PS ≥ 2 at the time of inclusion
- Age ≥ 70 years
Measured: From the date of first treatment administration until the date of death from any cause, assessed up to 7 years
ORR subgroup analysis according to Performance Status and age
ORR according to different subgroups :
- PS ≥ 2 at the time of inclusion
- Age ≥ 70 years
Measured: From the date of first treatment administration until the date of disease progression or death if patient died before progression) or the introduction of a new treatment, which ever occurs earlier, assessed up to 7 years
DCR subgroup analysis according to Performance Status and age
DCR according to different subgroups :
- PS ≥ 2 at the time of inclusion
- Age ≥ 70 years
Measured: From the date of first treatment administration until the date of disease progression (or death if patient died before progression), which ever occurs earlier, assessed up to 7 years
ic-ORR subgroup analysis according to Performance Status and age
ic-ORR according to different subgroups :
- PS ≥ 2 at the time of inclusion
- Age ≥ 70 years
Measured: From the date of first treatment administration until the date of disease progression (or death if patient died before progression), which ever occurs earlier, assessed up to 7 years
DOR subgroup analysis according to Performance Status and age
DOR according to different subgroups :
- PS ≥ 2 at the time of inclusion
- Age ≥ 70 years
Measured: From the date of first documented objective response (CR or PR) until disease progression or death, which ever occurs earlier, assessed up to 7 years
Duration of study treatment subgroup analysis according to Performance Status and age
Duration of treatment according to different subgroups :
- PS ≥ 2 at the time of inclusion
- Age ≥ 70 years
Measured: From the date of first treatment administration until the date of last treatment administration, up to 7 years
Toxicities occurring during study treatment assessed by the NCI-CTCAE v5.0, analysed in subgroups according to Performance Status and age
Proportion (%) of patients with any AE and number of events for all AEs, all SAEs and all AEs of grade ≥3 assessed by the NCI-CTCAE v5.0 criteria, according to different subgroups :
- PS ≥ 2 at the time of inclusion
- Age ≥ 70 years
Measured: From the date of first treatment administration up to 30 days after the last dose of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2024
- Study start1 Oct 2024
- Primary completionSep 2031 (estimated)
- Study completionSep 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NSCLC Stage IVStudies 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
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
- Sponsor type
- University, hospital or other
- Collaborators
- Groupe Francais De Pneumo-Cancerologie, Hospices Civils de Lyon
- Responsible party
- Sponsor
- Investigators
- Olivier BYLICKI, MD, PhD, PR, Study director, HIA Sainte Anne / Groupe Français d'Onco-PneumologieLaurent GREILLIER, MD, PhD, PR, Study director, AP-HM / Groupe Français d'Onco-Pneumologie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06552234
- Sponsor's protocol ID
- REPOROS GFPC 04-2023
- Other IDs
- 2023-509073-23-00, 2023
- Acronym
- REPOROS
- Status last verified
- Jul 2026
- First submitted
- 1 Aug 2024
- Last updated
- 7 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label Phase II Efficacy Study of Repotrectinib in Frail (PS ≥2) and/or Elderly Patients With ROS1-rearranged Advanced NSCLC
- ClinicalTrials.gov ID
- NCT06552234
- Acronym / sponsor ID
- REPOROS / REPOROS GFPC 04-2023
- Conditions
- NSCLC Stage IV, NSCLC, Stage III
- Keywords
- tyrosine-kinase inhibitors, Frail patients, Elderly patients, ROS1 rearrangements, resistance
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Centre Hospitalier Intercommunal de Toulon La Seyne sur MerUniversity, hospital or other
- Collaborators
- Groupe Francais De Pneumo-Cancerologie, Hospices Civils de Lyon
- Study start
- 1 Oct 2024 (actual)
- Primary completion
- Sep 2031 (estimated)
- Study completion
- Sep 2031 (estimated)
- First posted
- 13 Aug 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.
ROS1 rearrangements are rare, accounting for only 1-2% of NSCLC cases, but have been associated with response to ROS1 inhibitors, such as crizotinib and entrectinib. However, many patients develop resistance to the tyrosine-kinase inhibitors (TKIs), creating a need for new treatments.
Repotrectinib is a new-generation TKI designed against ROS1 or NTRK rearranged malignancies (Drilon 2018). Early phase clinical data support activity of repotrectinib in patients with NSCLC harboring such gene rearrangements (TRIDENT-1 study), but there are limited evidence in frail populations, such as poor performance status patients and/or elderly patients, who are classically excluded from clinical trials or underrepresented.
The present study aims to assess the activity and tolerability of repotrectinib in frail (PS ≥2) and/or elderly patients with ROS1-rearranged advanced NSCLC.
Detailed description
This is a national, multicenter, phase II, prospective, open label, non-randomized, interventional study.
Frail (PS≥2) and/or elderly patients (≥70 years) with histologically/cytologically proven stage IV or stage III non-eligible to local treatment NSCLC harboring an ROS1 gene rearrangement treated by Repotrectinib (160 mg twice a day (BID), until progression or unacceptable toxicity) in first or any line.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Repotrectinib treatment | Experimental | Drug: Repotrectinibpatient treated by Repotrectinib until progression or unacceptable toxicity |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (38 listed)
- Eligible patients are defined as patients with
- Age ≥ 18 years
- Histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC harboring an ROS1 gene rearrangement as by any nucleic acid-based diagnostic testing method (e.g., next-generation sequencing [NGS], Sanger sequencing, reverse transcription-polymerase chain reaction), Break-apart fluorescence in situ hybridization (FISH) or Immunohistochemistry (IHC) (confirmed by NGS or qPCR test).
- Willing and able to provide written institutional review board (IRB)/institutional ethics committee-approved Informed Consent.
- At least 1 measurable target lesion according to RECIST (v1.1). CNS-only measurable disease as defined by RECIST (v1.1) is allowed.
Key exclusion criteria (11 listed)
- Malignancies other than NSCLC within 2 years prior to inclusion, with the exception of those with a negligible risk of metastasis or death (e.g., expected 5-year OS ≥ 90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous-cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent)
- Patients with active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and absence of HBsAg) are eligible only if they are negative for HBV DNA. Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA.
- Active tuberculosis
- Severe infections within 2 weeks prior to inclusion, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
- Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction, or cerebrovascular accident within 3 months prior to inclusion, unstable arrhythmias, or unstable angina
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 |
|---|---|---|
| RepotrectinibRepotrectinib 160 mg BID, until progression or unacceptable toxicity | Drug | Repotrectinib treatment |
Primary outcome
Objective response rate (ORR) according to RECIST v1.1.
Time frame: From the date of first treatment administration until the date of disease progression or death if patient died before progression) or the introduction of a new treatment, which ever occurs earlier, assessed up to 7 years
ORR defined as the proportion of patients who achieved a complete or partial response according to RECIST v1.1 from the date of first treatment administration until disease progression or death if patient died before progression or the introduction of a new treatment assessed by blinded independent central review. Tumor assessments will be performed at Screening, every 2 Months during the first year then every 3 months thereafter until documented progression, death or the introduction of a new treatment. Patients who discontinue treatment for reasons other than radiographic disease progression per RECIST v1.1 (toxicity, symptomatic deterioration) will continue scheduled tumor assessments until radiographic disease progression per RECIST v1.1, withdrawal of consent, death, or study termination by the co-Sponsors, whichever occurs first
16 secondary outcomes
Progression free survival (PFS) by masked, independent central review
Time frame: From the date of first treatment administration until the date of disease progression (or death if patient died before progression), which ever occurs earlier, assessed up to 7 years
Disease control rate (DCR) by masked, independent central review
Time frame: From the date of first treatment administration until the date of disease progression (or death if patient died before progression), which ever occurs earlier, assessed up to 7 years
Intracranial ORR (ic-ORR) by masked, independent central review
Time frame: From the date of first treatment administration until the date of disease progression (or death if patient died before progression), which ever occurs earlier, assessed up to 7 years
Overall survival (OS)
Time frame: From the date of first treatment administration until the date of death from any cause, assessed up to 7 years
Toxicities occurring during either the induction or maintenance treatment in terms of kind, grade, time of onset, reversibility, according to NCI-CTCAE v5.0 criteria
Time frame: From the date of first treatment administration up to 30 days after the last dose of study treatment
Duration of response (DOR) assessed in patients who had an objective response as determined by the investigator using RECIST v1.1
Time frame: From the date of first documented objective response (CR or PR) until disease progression or death, which ever occurs earlier, assessed up to 7 years
Time to deterioration in lung-related symptoms
Time frame: From the date of inclusion to the date the patient's score on the EORTC QLQ C30 or QLQ-LC13 shows a ≥10-point increase above baseline, assessed up to 7 years
Time to deterioration in quality of life
Time frame: From the date of inclusion to the date the patient's score on the EQ-5D-3L utility score shows a 0.08 point decrease above baseline, assessed up to 7 years
PFS subgroup analysis according to Performance Status and age
Time frame: From the date of first treatment administration until the date of disease progression (or death if patient died before progression), which ever occurs earlier, assessed up to 7 years
OS subgroup analysis according to Performance Status and age
Time frame: From the date of first treatment administration until the date of death from any cause, assessed up to 7 years
ORR subgroup analysis according to Performance Status and age
Time frame: From the date of first treatment administration until the date of disease progression or death if patient died before progression) or the introduction of a new treatment, which ever occurs earlier, assessed up to 7 years
DCR subgroup analysis according to Performance Status and age
Time frame: From the date of first treatment administration until the date of disease progression (or death if patient died before progression), which ever occurs earlier, assessed up to 7 years
ic-ORR subgroup analysis according to Performance Status and age
Time frame: From the date of first treatment administration until the date of disease progression (or death if patient died before progression), which ever occurs earlier, assessed up to 7 years
DOR subgroup analysis according to Performance Status and age
Time frame: From the date of first documented objective response (CR or PR) until disease progression or death, which ever occurs earlier, assessed up to 7 years
Duration of study treatment subgroup analysis according to Performance Status and age
Time frame: From the date of first treatment administration until the date of last treatment administration, up to 7 years
Toxicities occurring during study treatment assessed by the NCI-CTCAE v5.0, analysed in subgroups according to Performance Status and age
Time frame: From the date of first treatment administration up to 30 days after the last dose of study treatment
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 7 Jul 2026.
- Individual participant dataSharing planned: No
Related trials for NSCLC Stage IV
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Active, not recruitingPhase 2
A Study of Investigational Agents in Participants With Previously Treated Stage IV Nonsquamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-01H/KEYMAKER-U01)
Carcinoma, Non-Small-Cell Lung
Active, not recruitingPhase 2
CAN-2409 Plus Prodrug With Standard of Care Immune Checkpoint Inhibitor for Stage III/IV NSCLC
Non Small Cell Lung Cancer
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.
Olivier BYLICKI, MD, PhD, PR study director
HIA Sainte Anne / Groupe Français d'Onco-Pneumologie
Laurent GREILLIER, MD, PhD, PR study director
AP-HM / Groupe Français d'Onco-Pneumologie
20 sites in 1 country: 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 Stage IV and NSCLC, Stage III, run by Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer at 20 sites in France.
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 38 inclusion and 11 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 7 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in France. 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 Sophie Lafond (0483772062 ext. +33, sophie.lafond@ch-toulon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (ORR) according to RECIST v1.1. (time frame: From the date of first treatment administration until the date of disease progression or death if patient died before progression) or the introduction of a new treatment, which ever occurs earlier, assessed up to 7 years). 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 7 Jul 2026.