Study of RP-3500 in Advanced Solid Tumours

Titre officiel

Phase 1/2a Study of the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Clinical Activity of RP-3500 Alone or in Combination With Talazoparib in Advanced Solid Tumours With ATR Inhibitor Sensitizing Mutations (TRESR Study)

Sommaire:

L’objectif principal de cette étude est d’étudier la dose maximale tolérée (DMT) de RP-3500 administré par voie orale, seul ou en association avec le talazoparib, un inhibiteur de la PARP, chez des patients atteints de tumeurs solides avancées présentant des mutations sensibilisant aux inhibiteurs de l’ataxie télangiectasie et de la protéine liée à Rad3. Cette étude évaluera également l’innocuité et la tolérabilité du RP-3500 seul ou en association avec le talazoparib, examinera la pharmacocinétique (PK) et la pharmacodynamique (PD) du RP-3500 et étudiera l’activité antitumorale de celui-ci dans les tumeurs solides.

Description de l'essai

Primary Outcome:

• To define the Maximum Tolerated Dose (MTD) which will then be used to inform and determine the Recommended Phase 2 Dose (RP2D) and schedule alone or in combination with talazoparib
• Frequency of Dose limiting Toxicities (DLTs)
• Safety and tolerability

Secondary Outcome:

• Assess preliminary anti-tumour activity with Overall Response Rate (ORR) in patients with eligible advanced solid tumours by CT/MRI Response evaluation criteria in solid tumours (RECIST 1.1).
• Assess preliminary anti-tumour activity with Duration of Response (DOR) in patients with eligible advanced solid tumours by CT/MRI Response evaluation criteria in solid tumours (RECIST 1.1).
• Characterize the pharmacokinetic profile of RP-3500
• Peak plasma concentration
• To assess PK parameters of RP-3500 monotherapy in fasted and fed states
• Pharmacodynamic biomarkers of DNA damage (e.g. gH2AX) will be measured by immunohistochemistry and the percentage of positive cells will be compared between the pre and post treatment biopsies to evaluate target engagement

This is a first-in-human, Phase 1/2, multi-centre, open-label, dose-escalation and expansion study to:

• Evaluate the safety profile and MTD of RP-3500 when administered orally, alone and in combination with talazoparib, to establish the dose and schedule recommended for the Phase 2

• Characterize the PK profile of RP-3500 alone or in combination with talazoparib

• Identify anti-tumour activity associated with RP-3500 given alone or in combination with talazoparib

• Examine biomarker responses and establish a correlation with RP-3500 treatment. The initial cohorts will test RP-3500 as monotherapy. Additional cohorts will be enrolled with RP-3500 in combination with a PARP inhibitor. After the RP2D and schedule is determined, expansion cohort(s) for RP-3500 will be enrolled to study the anti-tumour effect, and further examine the safety, PK, and PD of RP-3500 at the RP2D

Voir cet essai sur ClinicalTrials.gov