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

NCT ID: NCT06552234

Last Updated: 2025-11-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-10-01

Study Completion Date

2031-09-30

Brief Summary

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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

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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

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NSCLC Stage IV NSCLC, Stage III

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Repotrectinib treatment

patient treated by Repotrectinib until progression or unacceptable toxicity

Group Type EXPERIMENTAL

Repotrectinib

Intervention Type DRUG

Repotrectinib 160 mg BID, until progression or unacceptable toxicity

Interventions

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Repotrectinib

Repotrectinib 160 mg BID, until progression or unacceptable toxicity

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Groupe Francais De Pneumo-Cancerologie

OTHER

Sponsor Role collaborator

Hospices Civils de Lyon

OTHER

Sponsor Role collaborator

Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Olivier BYLICKI, MD, PhD, PR

Role: STUDY_DIRECTOR

HIA Sainte Anne / Groupe Français d'Onco-Pneumologie

Laurent GREILLIER, MD, PhD, PR

Role: STUDY_DIRECTOR

AP-HM / Groupe Français d'Onco-Pneumologie

Locations

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CH Aix-en-Provence

Aix-en-Provence, Bouches Du Rhône, France

Site Status RECRUITING

AP-HM

Marseille, Bouches Du Rhône, France

Site Status RECRUITING

HIA Sainte Anne

Toulon, Var, France

Site Status RECRUITING

CHU Angers

Angers, , France

Site Status RECRUITING

CHU Bordeaux

Bordeaux, , France

Site Status RECRUITING

CHU Brest

Brest, , France

Site Status RECRUITING

Centre François Baclesse

Caen, , France

Site Status RECRUITING

CH Chambéry

Chambéry, , France

Site Status RECRUITING

Hôpitaux civils de Colmar

Colmar, , France

Site Status RECRUITING

CHI Créteil

Créteil, , France

Site Status RECRUITING

CHD Vendée

La Roche-sur-Yon, , France

Site Status RECRUITING

CHRU Lille

Lille, , France

Site Status RECRUITING

CHU Limoges

Limoges, , France

Site Status RECRUITING

Hospices Civils de Lyon

Lyon, , France

Site Status RECRUITING

CH Cornouaille

Quimper, , France

Site Status RECRUITING

CHU Rennes

Rennes, , France

Site Status RECRUITING

CHU Rouen

Rouen, , France

Site Status RECRUITING

Hôpital Foch

Suresnes, , France

Site Status RECRUITING

CHU Toulouse

Toulouse, , France

Site Status RECRUITING

Hôpitaux Nord-Ouest

Villefranche-sur-Saône, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Sophie Lafond

Role: CONTACT

0483772062 ext. +33

Soizic Ferlandin

Role: CONTACT

0663224789 ext. +33

Facility Contacts

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Stéphanie MARTINEZ

Role: primary

Laurent GREILLIER

Role: primary

Olivier BYLICKI

Role: primary

Grégoire JUSTEAU

Role: primary

Claire BARDEL

Role: primary

Margaux GEIER

Role: primary

Pierre DEMONTROND

Role: primary

Julian PINSOLLE

Role: primary

Lionel MOREAU

Role: primary

Gaëlle ROUSSEAU BUSSAC

Role: primary

Acya BIZIEUX

Role: primary

Alexis CORTOT

Role: primary

Yannick SIMONNEAU, MD

Role: primary

05 55 05 55 55

Thomas PIERRET

Role: primary

Maël DOMBLIDES

Role: primary

Yannick LE GUEN

Role: primary

Florian GUISIER

Role: primary

Hélène DOUBRE

Role: primary

Laurence BIGAY-GAME

Role: primary

Lionel FALCHERO

Role: primary

Other Identifiers

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2023-509073-23-00

Identifier Type: CTIS

Identifier Source: secondary_id

REPOROS GFPC 04-2023

Identifier Type: -

Identifier Source: org_study_id

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