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

NCT06552234 | Recruiting Phase 2 DMC

• 2 other identifiers: REPOROS GFPC 04-20232023-509073-23-00
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 20

Brief 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. 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.

Conditions

NSCLC Stage IV; NSCLC, Stage III

Keywords

tyrosine-kinase inhibitors; Frail patients; Elderly patients; ROS1 rearrangements; resistance

Outcome Measures

Primary Outcomes (1)

• 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

  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

  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

  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

  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)

  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

  From the date of first treatment administration up to 30 days after the last dose of study treatment

Study Arms (1)

Repotrectinib treatment

EXPERIMENTAL

patient treated by Repotrectinib until progression or unacceptable toxicity

Drug: Repotrectinib

Interventions

Repotrectinib DRUG

Repotrectinib 160 mg BID, until progression or unacceptable toxicity

Repotrectinib treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible patients are defined as patients with
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer: lead
• Groupe Francais De Pneumo-Cancerologie: collaborator
• Hospices Civils de Lyon: collaborator

Study Sites (20)

CH Aix-en-Provence

Aix-en-Provence, Bouches Du Rhône, France

RECRUITING

AP-HM

Marseille, Bouches Du Rhône, France

RECRUITING

HIA Sainte Anne

Toulon, Var, France

RECRUITING

CHU Angers

Angers, France

RECRUITING

CHU Bordeaux

Bordeaux, France

RECRUITING

CHU Brest

Brest, France

RECRUITING

Centre François Baclesse

Caen, France

RECRUITING

CH Chambéry

Chambéry, France

RECRUITING

Hôpitaux civils de Colmar

Colmar, France

RECRUITING

CHI Créteil

Créteil, France

RECRUITING

CHD Vendée

La Roche-sur-Yon, France

RECRUITING

CHRU Lille

Lille, France

RECRUITING

CHU Limoges

Limoges, France

RECRUITING

Hospices Civils de Lyon

Lyon, France

RECRUITING

CH Cornouaille

Quimper, France

RECRUITING

CHU Rennes

Rennes, France

RECRUITING

CHU Rouen

Rouen, France

RECRUITING

Hôpital Foch

Suresnes, France

RECRUITING

CHU Toulouse

Toulouse, France

RECRUITING

Hôpitaux Nord-Ouest

Villefranche-sur-Saône, France

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

repotrectinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Olivier BYLICKI, MD, PhD, PR

  HIA Sainte Anne / Groupe Français d'Onco-Pneumologie

  STUDY DIRECTOR

• Laurent GREILLIER, MD, PhD, PR

  AP-HM / Groupe Français d'Onco-Pneumologie

  STUDY DIRECTOR

Central Study Contacts

Sophie Lafond

CONTACT

0483772062; sophie.lafond@ch-toulon.fr

Soizic Ferlandin

CONTACT

0663224789; soizic_ferlandin@yahoo.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2024
• First Posted: August 13, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): September 1, 2031
• Study Completion (Estimated): September 1, 2031
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (20)