Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With R/R DLBCL or R/R CLL

Phase 1

• Conditions: Chronic Lymphocytic Leukemia; Non Hodgkin Lymphoma; Diffuse Large B Cell Lymphoma
• Interventions: Drug: KRT-232; Drug: acalabrutinib

• Registration Number: NCT04502394
• Lead Sponsor: Kartos Therapeutics, Inc.

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)

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-07-27
• Study First Submitted QC: 2020-08-05
• Study First Posted: 2020-08-06
• Study Start: 2021-02-23
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-03
• Last Update Posted: 2022-08-04
• Primary Completion: 2022-10
• Study Completion: 2024-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 84

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1 (R/R DLBCL)	KRT-232	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)	KRT-232	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)	acalabrutinib	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 1 (R/R DLBCL)	acalabrutinib	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 parameters from a single dose will be apparent volume of distribution using non-compartmental or compartmental PK methods with the software WinNonlin.
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

Trial Locations

Locations (45)

Goshen Center for Cancer Care; 🇺🇸 Goshen, Indiana, United States

University of Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

The Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Royal Adelaide Hospital; 🇦🇺 Adelaide, Australia

Eastern Health - Box Hill Hospital; 🇦🇺 Box Hill, Australia

Barwon Health; 🇦🇺 Geelong, Australia

Royal Perth Hospital; 🇦🇺 Perth, Australia

Antwerp University Hospital (UZA); 🇧🇪 Edegem, Belgium

Jessa Ziekenhuis; 🇧🇪 Hasselt, Belgium

Scroll for more (35 remaining)