Phase II Efficacy Study of Repotrectinib in Frail and/or Elderly Patients With ROS1-rearranged Advanced NSCLC

Recruiting now · Phase 2

Conditions studied: NSCLC Stage IV, NSCLC, Stage III

In brief

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.

Key facts

Study ID

NCT06552234

Run by

Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer

People needed

30

Starts

2024-10-01

Expected to finish

2031-09-01

Last updated by the study team

2026-07-07

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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

You may not qualify if…

• 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 it is running

• CH Aix-en-Provence — Aix-en-Provence, Bouches Du Rhône, France (enrolling)
• AP-HM — Marseille, Bouches Du Rhône, France (enrolling)
• HIA Sainte Anne — Toulon, Var, France (enrolling)
• CHU Angers — Angers, France (enrolling)
• CHU Bordeaux — Bordeaux, France (enrolling)
• CHU Brest — Brest, France (enrolling)
• Centre François Baclesse — Caen, France (enrolling)
• CH Chambéry — Chambéry, France (enrolling)
• Hôpitaux civils de Colmar — Colmar, France (enrolling)
• CHI Créteil — Créteil, France (enrolling)
• CHD Vendée — La Roche-sur-Yon, France (enrolling)
• CHRU Lille — Lille, France (enrolling)
• CHU Limoges — Limoges, France (enrolling)
• Hospices Civils de Lyon — Lyon, France (enrolling)
• CH Cornouaille — Quimper, France (enrolling)
• CHU Rennes — Rennes, France (enrolling)
• CHU Rouen — Rouen, France (enrolling)
• Hôpital Foch — Suresnes, France (enrolling)
• CHU Toulouse — Toulouse, France (enrolling)
• Hôpitaux Nord-Ouest — Villefranche-sur-Saône, France (enrolling)

Full record on ClinicalTrials.gov

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