Diffuse Large B Cell Lymphoma, Chronic Lymphocytic Leukemia, Non Hodgkin Lymphoma
Conditions
Keywords
navtemadlin
Brief summary
This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, combined with acalabrutinib for the treatment of adults with Diffuse Large B-Cell Lymphoma and Chronic Lymphocytic Leukemia. Participants must be relapsed/refractory (having failed prior therapy)
Interventions
DRUGKRT-232
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth
DRUGacalabrutinib
acalabrutinib is a BTK inhibitor anticancer drug taken by mouth
Sponsors
Kartos Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
An Open-label, Phase 1b/2 Study of KRT-232 in combination with acalabrutinib in Subjects with B-cell Non-Hodgkin Lymphoma
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Cohort 1: Confirmed diagnosis of TP53wt DLBCL (WHO); R/R DLBCL after at least 2 prior lines of treatment or 1 prior for patients who are ineligible for stem cell transplant * Cohort 2: Confirmed diagnosis of TP53wt CLL (iwCLL); R/R CLL after at least 1 prior line of treatment * ECOG 0 to 2 * Adequate hematologic, hepatic, and renal functions.
Exclusion criteria
* Prior treatment with any MDM2 inhibitor * Prior treatment with any BTK inhibitor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Objective Phase 1b:To determine the KRT-232 maximum tolerated dose/ maximum administered dose (MTD/MAD) and recommended Phase 2 Dose (RP2D) in combination with acalabrutinib in subjects with R/R DLBCL or R/R CLL | 56 Days | Endpoint/Outcome Measures: Dose-limiting toxicities will be used to establish the MTD/MAD of KRT-232 in combination with acalabrutinib. The Safety Review Committee will determine the RP2D based on safety data of the combination of KRT-232 and acalabrutinib. |
| Primary Objective Phase 2: Cohort 1: To determine the complete response (CR) | 1 Year | Endpoint/Outcome Measures: Cohort 1: The proportion of subjects with CR as assessed by investigators per the Lugano Classification. |
| Primary Objective Phase 2: Cohort 2: To determine the rate of CR/complete remission with incomplete hematologic recovery (CRi) rate in R/R CLL | 1 Year | Endpoint/Outcome Measures: Cohort 2: The proportion of subjects with CR/CRi as assessed by investigators per iwCLL Response Criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b Secondary Objective: Pharmacokinetic (PK) profile | Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2 | Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameter from a single dose will be estimated maximum concentration (Cmax). |
| Phase 2 Secondary Objective: Cohort 1 (R/R DLBCL): To determine the overall response rate (ORR) for R/R DLBCL subjects. | 2 Years | Endpoint/Outcome Measures: The proportion of subjects who achieve a partial response (PR) or better at any time point while on study. |
| Phase 2 Secondary Objective: Cohort 2 (R/R CLL): To determine the ORR for R/R CLL subjects | 2 Years | Endpoint/Outcome Measures: The proportion of subjects who achieve a PR or better at any time point while on study, as assessed by iwCLL Response Criteria |
Countries
Australia, Belgium, Czechia, France, Italy, Poland, Portugal, South Korea, Switzerland, United Kingdom, United States
Contacts
Primary ContactJohn Mei
Backup ContactMichael Yee
Outcome results
None listed