Criterios de inclusión clave:
1. Se requiere una mutación puntual, una fusión o una amplificación genética documentada de ROS1, o una fusión genética de NTRK1-3 según lo
identificado por las pruebas locales en un laboratorio acreditado en virtud de las Enmiendas para la Mejora de los Laboratorios Clínicos (CLIA)
en los EE. UU. o en un laboratorio
de diagnóstico con una acreditación equivalente fuera de los Estados Unidos (EE. UU.).
2. Fase 1: Edad <12 years; Phase 2: Age 12- 25 years
3. Prior cytotoxic chemotherapy is allowed.
4. Prior immunotherapy is allowed.
5. Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer
therapy to National Cancer Institute Common Terminology Criteria for Adverse Events
(NCI CTCAE) Version 4.03 Grade less than or equal to 1.
6. All subjects must have measurable disease by RECIST v1.1 or Response Assessment in
Neuro-Oncology (RANO) criteria at time of enrollment.
7. Subjects with a primary CNS tumor or CNS metastases must be neurologically stable on a
stable or decreasing dose of steroids for at least 7 days prior to enrollment.
8. Subjects must have a Lansky (< 16 years) or Karnofsky (≥ 16 years) score of at least
50.
9. Life expectancy greater than or equal to 12 weeks, in the investigator's opinion.
10. Adequate hematologic, renal and hepatic function.
Phase 2 Inclusion Criteria:
1. Cohort Specific Inclusion Criteria:
- Cohort 1: Subjects with NTRK fusion gene positive (NTRK+) advanced solid tumors
(including primary CNS tumors), that are tropomyosin receptor kinase (TRK) TKI
naïve;
- Cohort 2: subjects with NTRK+ advanced solid tumors (including primary CNS
tumors), that are TRK TKI pre-treated;
- Cohort 3: subjects with advanced solid tumors with ROS1 gene fusions or other
ROS1 aberrations (including amplifications and point mutations) with measurable
disease.
2. Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by
BICR prior to enrollment.
Key Exclusion Criteria (Phase 1 and Phase 2):
1. Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow
aspiration only.
2. Major surgery within 14 days (2 weeks) of start of repotrectinib treatment. Central
venous access (Broviac, Mediport, etc.) placement does not meet criteria for major
surgery.
3. Known active infections requiring ongoing treatment (bacterial, fungal, viral
including HIV positivity).
4. Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut
syndrome) or other malabsorption syndromes that would impact drug absorption.
5. Any of the following cardiac criteria:
- Mean resting corrected QT interval (ECG interval measured from the onset of the
QRS complex to the end of the T wave) for heart rate (QTc)> 480 ms obtenido
de tres ECG, usando el valor del QTc derivado de la máquina de ECG de la clínica de selección.
- Cualquier anomalía clínicamente importante en el ritmo, la conducción o la morfología del
ECG en reposo (p. ej., bloqueo completo de rama izquierda, bloqueo cardíaco de tercer grado,
bloqueo cardíaco de segundo grado, intervalo PR >250 ms).
- Cualquier factor que aumente el riesgo de prolongación del intervalo QTc o el riesgo de eventos arrítmicos,
como insuficiencia cardíaca, síndrome congénito de prolongación del intervalo QT, antecedentes familiares de síndrome de prolongación del intervalo QT,
o cualquier medicamento concomitante que se sepa que prolonga el intervalo QT.
6. Neuropatía periférica de grado ≥2 según los CTCAE.
7. Sujetos que reciben tratamiento con inhibidores o inductores potentes de CYP3A4
o que prevén la necesidad de dicho tratamiento.
8. Cualquier posible alergia al repotrectinib o a sus excipientes.
Recruiting
