Home › Trials › NCT06552234

Testing Repotrectinib in Elderly and Frail Patients with Advanced NSCLC

Open-label Phase II Efficacy Study of Repotrectinib in Frail (PS ≥2) and/or Elderly Patients With ROS1-rearranged Advanced NSCLC

Phase 2 Interventional Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer · NCT06552234

This study is testing a new cancer drug called repotrectinib to see if it helps older and frail patients with advanced lung cancer feel better and tolerate the treatment well.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment30 (estimated)
Ages18 Years and up
SexAll
SponsorCentre Hospitalier Intercommunal de Toulon La Seyne sur Mer Academic / other
Drugs / interventionsrepotrectinib, crizotinib, ceritinib, lorlatinib, brigatinib, entrectinib, ensartinib, cabozantinib, chemotherapy, immunotherapy, doxorubicin
Locations20 sites (Aix-en-Provence, Bouches Du Rhône and 19 other locations)
Trial IDNCT06552234 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial evaluates the efficacy and tolerability of repotrectinib, a new-generation tyrosine-kinase inhibitor, in frail and elderly patients with ROS1-rearranged advanced non-small cell lung cancer (NSCLC). The study focuses on patients who are typically underrepresented in clinical trials, specifically those with a performance status of 2 or higher and those aged 70 years or older. Participants will receive repotrectinib at a dosage of 160 mg twice daily until disease progression or unacceptable toxicity occurs. The trial aims to provide insights into the treatment's effectiveness in this vulnerable population.

Who should consider this trial

Good fit: Ideal candidates include frail patients with a performance status of 2 or higher and elderly patients aged 70 years or older with ROS1-rearranged advanced NSCLC.

Not a fit: Patients with NSCLC that does not have ROS1 rearrangements or those who are not frail or elderly may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new therapeutic option for frail and elderly patients with advanced NSCLC who have limited treatment choices.

How similar studies have performed: While early phase studies have shown promise for repotrectinib in ROS1-rearranged NSCLC, this specific focus on frail and elderly populations is relatively novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* 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.
* 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

Exclusion Criteria:

* 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
* 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

Where this trial is running

Aix-en-Provence, Bouches Du Rhône and 19 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions NSCLC Stage IVNSCLC, Stage IIItyrosine-kinase inhibitorsFrail patientsElderly patientsROS1 rearrangementsresistance
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.