Phase 1/2 Study of VIP152, Venetoclax, and Prednisone (VVIP) in Relapsed/Refractory Lymphoid Malignancies
Status:
Not yet recruiting
Trial end date:
2025-03-10
Target enrollment:
Participant gender:
Summary
Background:
- High unmet medical need for relapsed/refractory non-Hodgkin lymphoma (NHL) after
exhausting chemotherapy and/or chemo- immunotherapy regimens
- Targeted therapies aimed at disrupting cell death pathway in hematologic malignancies
are emerging and showing significant activity in both the relapsed and first-line
settings
- VIP152 is a selective inhibitor of PTEFb/CDK9 and is expected to show efficacy in tumor
indications that overexpress MYC and MCL-1. VIP152 monotherapy has demonstrated a mild
toxicity profile and preliminary efficacy in Phase 1 studies in advanced cancer
- The combination of VIP152 with venetoclax and prednisone (VVIP) targets major celldeath
pathways in lymphoid malignancies (BCL-2 and MCL-1) and may overcome chemo-resistance
and/or single drug resistance to venetoclax
Objectives:
- Phase 1: To determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D),
and the safety and toxicity profile of the combination of VIP152 with venetoclax and
prednisone (VVIP) in relapsed/refractory lymphoid malignancies
- Phase 2: To determine the complete response (CR) rate of the combination of VIP152 with
venetoclax and prednisone (VVIP) in R/R lymphoid malignancies
Eligibility:
- Women and men >= 18 years of age
- ECOG performance status of <= 2
- Histologically or cytologically confirmed relapsed and/or refractory NHL
- Adequate organ function unless dysfunction secondary to disease effect
Design:
- Open-label, single-center, non-randomized Phase 1/2 study
- Phase 1: Standard 3 + 3 design will be used to determine the MTD and RP2D of
doseescalated VIP152 and venetoclax with fixed dose prednisone in relapsed/refractory
lymphoid malignancies
- Phase 2: Expansion cohorts of defined aggressive NHL subtypes will be treated at the
RP2D to determine the ORR and CR rate in these disease groups
- Up to 24 cycles of combination targeted therapy given in 21-day cycles with the option
to stop therapy after 12 cycles if in CR following cycles 6 and/or 12 of therapy.
- To explore all dose levels of VIP152 and venetoclax in combination prednisone (VVIP) in
R/R NHL in the Phase 1 study (24 participants max) and to assess the CR rate in 3
defined cohorts of aggressive NHL in a Phase 2 dose expansion (3 cohorts x 29
participants = 87 participants max) at RP2D, the accrual ceiling will be set at 130
participants