Description:
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)
Title
- Brief Title: Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With R/R DLBCL or R/R CLL
- Official Title: An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With Relapsed/Refractory Diffuse Large B-cell Lymphoma or Relapsed/Refractory Chronic Lymphocytic Leukemia
Clinical Trial IDs
- ORG STUDY ID:
KRT-232-111
- NCT ID:
NCT04502394
Conditions
- Diffuse Large B Cell Lymphoma
- Chronic Lymphocytic Leukemia
- Non Hodgkin Lymphoma
Interventions
Drug | Synonyms | Arms |
---|
KRT-232 | | Cohort 1 (R/R DLBCL) |
acalabrutinib | ACP-196 | Cohort 1 (R/R DLBCL) |
Purpose
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)
Trial Arms
Name | Type | Description | Interventions |
---|
Cohort 1 (R/R DLBCL) | Experimental | KRT-232 will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle.
Acalabrutinib at 100 mg twice a day (BID) continuously starting on Day 1 in a 28-day cycle. | |
Cohort 2 (R/R CLL) | Experimental | KRT-232 will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle.
Acalabrutinib at 100 mg twice a day (BID) continuously starting on Day 1 in a 28-day cycle. | |
Eligibility Criteria
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | 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 |
Time Frame: | 56 Days |
Safety Issue: | |
Description: | 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. |
Secondary Outcome Measures
Measure: | Phase 1b Secondary Objective: Pharmacokinetic (PK) profile |
Time Frame: | 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 |
Safety Issue: | |
Description: | 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). |
Measure: | Phase 1b Secondary Objective: Pharmacokinetic (PK) profile |
Time Frame: | 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 |
Safety Issue: | |
Description: | 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 parameters from a single dose will be area under the curve (AUC). |
Measure: | Phase 1b Secondary Objective: Pharmacokinetic (PK) profile |
Time Frame: | 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 |
Safety Issue: | |
Description: | 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 parameters from a single dose will be half-life (T1/2). |
Measure: | Phase 1b Secondary Objective: Pharmacokinetic (PK) profile |
Time Frame: | 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 |
Safety Issue: | |
Description: | 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 apparent clearance. |
Measure: | Phase 1b Secondary Objective: Pharmacokinetic (PK) profile |
Time Frame: | 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 |
Safety Issue: | |
Description: | 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 parameters from a single dose will be apparent volume of distribution using non-compartmental or compartmental PK methods with the software WinNonlin. |
Measure: | Phase 2 Secondary Objective: Cohort 1 (R/R DLBCL): To determine the overall response rate (ORR) for R/R DLBCL subjects. |
Time Frame: | 2 Years |
Safety Issue: | |
Description: | Endpoint/Outcome Measures: The proportion of subjects who achieve a partial response (PR) or better at any time point while on study. |
Measure: | Phase 2 Secondary Objective: Cohort 2 (R/R CLL): To determine the ORR for R/R CLL subjects |
Time Frame: | 2 Years |
Safety Issue: | |
Description: | 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 |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Kartos Therapeutics, Inc. |
Trial Keywords
Last Updated
August 5, 2021