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

Primary Purpose

Diffuse Large B Cell Lymphoma, Chronic Lymphocytic Leukemia, Non Hodgkin Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
KRT-232
acalabrutinib
Sponsored by
Kartos Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B Cell Lymphoma focused on measuring navtemadlin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Goshen Center for Cancer CareRecruiting
  • University of CincinnatiRecruiting
  • The Ohio State University Comprehensive Cancer CenterRecruiting
  • UT Southwestern Medical CenterRecruiting
  • Royal Adelaide HospitalRecruiting
  • Eastern Health - Box Hill HospitalRecruiting
  • Barwon HealthRecruiting
  • Royal Perth HospitalRecruiting
  • Antwerp University Hospital (UZA)Recruiting
  • Jessa ZiekenhuisRecruiting
  • University Hospital (UZ) LeuvenRecruiting
  • Fakultni Nemocnice Hradec KraloveRecruiting
  • Fakultni nemocnice OstravaRecruiting
  • Vseobecna fakultni nemocnice v PrazeRecruiting
  • CHU de Nantes - Hôtel-DieuRecruiting
  • Centre Henri BecquerelRecruiting
  • CHRU de Tours - Hôpital BretonneauRecruiting
  • Centro Riferimento Oncologico - AvianoRecruiting
  • Istituto Scientifico Romagnolo per lo Studio e la Cura dei TumoriRecruiting
  • ASST Grande Ospedale Metropolitano NiguardaRecruiting
  • IRCCS Ospedale San RaffaeleRecruiting
  • Fondazione IRCCS Policlinico San MatteoRecruiting
  • Centro Ricerche Cliniche di Verona s.r.l.Recruiting
  • National Cancer CenterRecruiting
  • Gachon University Gil Medical CenterRecruiting
  • Samsung Medical CenterRecruiting
  • Seoul National University HospitalRecruiting
  • Seoul St. Mary's HospitalRecruiting
  • Severance Hospital, Yonsei University Health SystemRecruiting
  • Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i TransplantologiiRecruiting
  • Copernicus PL Sp. z o.o., Wojewodzkie Centrum OnkologiiRecruiting
  • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach - Klinika Transplantacji Szpiku i OnkohematologiiRecruiting
  • Szpital Uniwersytecki Krakow - Oddzial Kliniczny HematologiiRecruiting
  • Pratia MCM KrakowRecruiting
  • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we WroclawiuRecruiting
  • Hospital de BragaRecruiting
  • Centro Hospitalar Universitario de Lisboa Norte - Hospital de Santa MariaRecruiting
  • Champalimaud Cancer CenterRecruiting
  • Instituto Portugues de Oncologia do Porto Francisco Gentil, EPERecruiting
  • Centro Hospitalar de Vila Nova de Gaia/Espinho EPERecruiting
  • Kantonsspital St. GallenRecruiting
  • St James's University HospitalRecruiting
  • King's College HospitalRecruiting
  • Royal Marsden Foundation TrustRecruiting
  • University Hospital Southampton NHS Foundation TrustRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cohort 1 (R/R DLBCL)

Cohort 2 (R/R CLL)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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
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)
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
Endpoint/Outcome Measures: Cohort 2: The proportion of subjects with CR/CRi as assessed by investigators per iwCLL Response Criteria.

Secondary Outcome Measures

Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
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 1b Secondary Objective: Pharmacokinetic (PK) profile
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).
Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
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).
Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
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.
Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
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.
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
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

Full Information

First Posted
July 27, 2020
Last Updated
August 3, 2022
Sponsor
Kartos Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04502394
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 23, 2021 (Actual)
Primary Completion Date
October 2022 (Anticipated)
Study Completion Date
March 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kartos Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B Cell Lymphoma, Chronic Lymphocytic Leukemia, Non Hodgkin Lymphoma
Keywords
navtemadlin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
An Open-label, Phase 1b/2 Study of KRT-232 in combination with acalabrutinib in Subjects with B-cell Non-Hodgkin Lymphoma
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
84 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1 (R/R DLBCL)
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 2 (R/R CLL)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
KRT-232
Intervention Description
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth
Intervention Type
Drug
Intervention Name(s)
acalabrutinib
Other Intervention Name(s)
ACP-196
Intervention Description
acalabrutinib is a BTK inhibitor anticancer drug taken by mouth
Primary Outcome Measure Information:
Title
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
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.
Time Frame
56 Days
Title
Primary Objective Phase 2: Cohort 1: To determine the complete response (CR)
Description
Endpoint/Outcome Measures: Cohort 1: The proportion of subjects with CR as assessed by investigators per the Lugano Classification.
Time Frame
1 Year
Title
Primary Objective Phase 2: Cohort 2: To determine the rate of CR/complete remission with incomplete hematologic recovery (CRi) rate in R/R CLL
Description
Endpoint/Outcome Measures: Cohort 2: The proportion of subjects with CR/CRi as assessed by investigators per iwCLL Response Criteria.
Time Frame
1 Year
Secondary Outcome Measure Information:
Title
Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
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).
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
Title
Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
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).
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
Title
Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
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).
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
Title
Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
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.
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
Title
Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
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.
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
Title
Phase 2 Secondary Objective: Cohort 1 (R/R DLBCL): To determine the overall response rate (ORR) for R/R DLBCL subjects.
Description
Endpoint/Outcome Measures: The proportion of subjects who achieve a partial response (PR) or better at any time point while on study.
Time Frame
2 Years
Title
Phase 2 Secondary Objective: Cohort 2 (R/R CLL): To determine the ORR for R/R CLL subjects
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
Time Frame
2 Years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
John Mei
Phone
650-542-0136
Email
jmei@kartosthera.com
First Name & Middle Initial & Last Name or Official Title & Degree
Michael Yee
Phone
650-839-7361
Email
myee@kartosthera.com
Facility Information:
Facility Name
Goshen Center for Cancer Care
City
Goshen
State/Province
Indiana
ZIP/Postal Code
46526
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45221
Country
United States
Individual Site Status
Recruiting
Facility Name
The Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Recruiting
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Individual Site Status
Recruiting
Facility Name
Royal Adelaide Hospital
City
Adelaide
Country
Australia
Individual Site Status
Recruiting
Facility Name
Eastern Health - Box Hill Hospital
City
Box Hill
Country
Australia
Individual Site Status
Recruiting
Facility Name
Barwon Health
City
Geelong
Country
Australia
Individual Site Status
Recruiting
Facility Name
Royal Perth Hospital
City
Perth
Country
Australia
Individual Site Status
Recruiting
Facility Name
Antwerp University Hospital (UZA)
City
Edegem
Country
Belgium
Individual Site Status
Recruiting
Facility Name
Jessa Ziekenhuis
City
Hasselt
Country
Belgium
Individual Site Status
Recruiting
Facility Name
University Hospital (UZ) Leuven
City
Leuven
Country
Belgium
Individual Site Status
Recruiting
Facility Name
Fakultni Nemocnice Hradec Kralove
City
Nový Hradec Králové
Country
Czechia
Individual Site Status
Recruiting
Facility Name
Fakultni nemocnice Ostrava
City
Ostrava
Country
Czechia
Individual Site Status
Recruiting
Facility Name
Vseobecna fakultni nemocnice v Praze
City
Prague
Country
Czechia
Individual Site Status
Recruiting
Facility Name
CHU de Nantes - Hôtel-Dieu
City
Nantes
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Henri Becquerel
City
Rouen
Country
France
Individual Site Status
Recruiting
Facility Name
CHRU de Tours - Hôpital Bretonneau
City
Tours
Country
France
Individual Site Status
Recruiting
Facility Name
Centro Riferimento Oncologico - Aviano
City
Aviano
Country
Italy
Individual Site Status
Recruiting
Facility Name
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
City
Meldola
Country
Italy
Individual Site Status
Recruiting
Facility Name
ASST Grande Ospedale Metropolitano Niguarda
City
Milano
Country
Italy
Individual Site Status
Recruiting
Facility Name
IRCCS Ospedale San Raffaele
City
Milano
Country
Italy
Individual Site Status
Recruiting
Facility Name
Fondazione IRCCS Policlinico San Matteo
City
Pavia
Country
Italy
Individual Site Status
Recruiting
Facility Name
Centro Ricerche Cliniche di Verona s.r.l.
City
Verona
Country
Italy
Individual Site Status
Recruiting
Facility Name
National Cancer Center
City
Goyang
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Gachon University Gil Medical Center
City
Incheon
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Samsung Medical Center
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Seoul National University Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Seoul St. Mary's Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Severance Hospital, Yonsei University Health System
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii
City
Gdansk
Country
Poland
Individual Site Status
Recruiting
Facility Name
Copernicus PL Sp. z o.o., Wojewodzkie Centrum Onkologii
City
Gdańsk
Country
Poland
Individual Site Status
Recruiting
Facility Name
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach - Klinika Transplantacji Szpiku i Onkohematologii
City
Gliwice
Country
Poland
Individual Site Status
Recruiting
Facility Name
Szpital Uniwersytecki Krakow - Oddzial Kliniczny Hematologii
City
Krakow
Country
Poland
Individual Site Status
Recruiting
Facility Name
Pratia MCM Krakow
City
Kraków
Country
Poland
Individual Site Status
Recruiting
Facility Name
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
City
Wroclaw
Country
Poland
Individual Site Status
Recruiting
Facility Name
Hospital de Braga
City
Braga
Country
Portugal
Individual Site Status
Recruiting
Facility Name
Centro Hospitalar Universitario de Lisboa Norte - Hospital de Santa Maria
City
Lisboa
Country
Portugal
Individual Site Status
Recruiting
Facility Name
Champalimaud Cancer Center
City
Lisbon
Country
Portugal
Individual Site Status
Recruiting
Facility Name
Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE
City
Porto
Country
Portugal
Individual Site Status
Recruiting
Facility Name
Centro Hospitalar de Vila Nova de Gaia/Espinho EPE
City
Vila Nova de Gaia
Country
Portugal
Individual Site Status
Recruiting
Facility Name
Kantonsspital St. Gallen
City
Saint Gallen
Country
Switzerland
Individual Site Status
Recruiting
Facility Name
St James's University Hospital
City
Leeds
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
King's College Hospital
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Royal Marsden Foundation Trust
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
University Hospital Southampton NHS Foundation Trust
City
Southampton
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

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

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