Phase I Study of Repotrectinib and Osimertinib in NSCLC Patients

Sponsor
Instituto Oncológico Dr Rosell
Study ID
NCT04772235
Phase
PHASE1
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Repotrectinib — DRUG
    Repotrectinib will be taken orally once daily with or without food Part A: Dose escalation phase, with 3 dose levels for repotrectinib: (1) 80 mg QD, (2) 160 mg QD and (3) 160 mg QD for 14 days followed by 160 mg BID; in combination with 80 mg QD of osimertinib Part B: at the RP2D for all patients in combination with osimertinib.
  • Osimertinib — DRUG
    Osimertinib will be taken orally at 80 mg once daily with or without food. Part A: lead in dose in monotherapy at 80 mg QD during 14 days. In combination with repotrectinib afterwards. Depending on the safety and PK/ dose dependent interactions (DDIs) readout during the DLT assessment period, osimertinib dose may be adjusted. Part B: at the RP2D level in combination with repotrectinib

Study Details

This is a Phase I study of repotrectinib in combination with osimertinib in patients with advanced or metastatic EGFR mutant non small cell lung cancer (NSCLC). The study will be conducted in 2 parts, Part Ia and Part Ib, and its purpose will be to find the incidence of dose-limiting toxicities (DLTs) as defined by the primary safety and tolerability endpoint. The Phase Ia study will also determine the impact of repotrectinib on osimertinib pharmacokinetics (PK) and the maximum tolerated dose (MTD), if reached, of repotrectinib given in combination with osimertinib and the recommended Phase II dose (RP2D). Dose escalation will be conducted according to a 'Rolling-6' based study design with 3 dose levels for repotrectinib: 80 mg once a day (QD), 160 mg QD or 160 mf QD during 14 days followed by 160 mg twice a day (BID); in combination with 80 mg QD of osimertinib. A total of 6 patients will be enrolled in each dose level cohort. In addition, this Phase Ib study will test early drug activity (efficacy) of the proposed combination treatment in an expansion cohort at the RP2D.

Key Dates

Start date
Feb 11, 2022
Status verified
Apr 2024
Primary completion
Apr 30, 2026
Completion
Jun 30, 2026

Study Design

Enrollment
32 participants (estimated)
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Advanced and/or metastatic EGFR mutant NSCLC
    Eligible advanced and/or metastatic EGFR mutant NSCLC patients will receive the combination of osimertinib and repotrectinib.

Primary Outcome Measure

Adverse events (AEs) [ Time Frame: Throughout the study period. Approximately 48 months ]

Central Contacts

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