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

Sponsor
Kartos Therapeutics, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04502394
Collaborator
(none)
84
45
2
36.2
1.9
0.1

Study Details

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)

Study Design

Study Type:
Interventional
Anticipated Enrollment :
84 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
An Open-label, Phase 1b/2 Study of KRT-232 in combination with acalabrutinib in Subjects with B-cell Non-Hodgkin LymphomaAn 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)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Feb 23, 2021
Anticipated Primary Completion Date :
Oct 1, 2022
Anticipated Study Completion Date :
Mar 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cohort 1 (R/R DLBCL)

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.

Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth

Drug: acalabrutinib
acalabrutinib is a BTK inhibitor anticancer drug taken by mouth
Other Names:
  • ACP-196
  • Experimental: Cohort 2 (R/R CLL)

    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.

    Drug: KRT-232
    KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth

    Drug: acalabrutinib
    acalabrutinib is a BTK inhibitor anticancer drug taken by mouth
    Other Names:
  • ACP-196
  • Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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.

    3. 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

    1. 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).

    2. 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 area under the curve (AUC).

    3. 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 half-life (T1/2).

    4. 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 apparent clearance.

    5. 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.

    6. 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.

    7. 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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Goshen Center for Cancer Care Goshen Indiana United States 46526
    2 University of Cincinnati Cincinnati Ohio United States 45221
    3 The Ohio State University Comprehensive Cancer Center Columbus Ohio United States 43210
    4 UT Southwestern Medical Center Dallas Texas United States 75390
    5 Royal Adelaide Hospital Adelaide Australia
    6 Eastern Health - Box Hill Hospital Box Hill Australia
    7 Barwon Health Geelong Australia
    8 Royal Perth Hospital Perth Australia
    9 Antwerp University Hospital (UZA) Edegem Belgium
    10 Jessa Ziekenhuis Hasselt Belgium
    11 University Hospital (UZ) Leuven Leuven Belgium
    12 Fakultni Nemocnice Hradec Kralove Nový Hradec Králové Czechia
    13 Fakultni nemocnice Ostrava Ostrava Czechia
    14 Vseobecna fakultni nemocnice v Praze Prague Czechia
    15 CHU de Nantes - Hôtel-Dieu Nantes France
    16 Centre Henri Becquerel Rouen France
    17 CHRU de Tours - Hôpital Bretonneau Tours France
    18 Centro Riferimento Oncologico - Aviano Aviano Italy
    19 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori Meldola Italy
    20 ASST Grande Ospedale Metropolitano Niguarda Milano Italy
    21 IRCCS Ospedale San Raffaele Milano Italy
    22 Fondazione IRCCS Policlinico San Matteo Pavia Italy
    23 Centro Ricerche Cliniche di Verona s.r.l. Verona Italy
    24 National Cancer Center Goyang Korea, Republic of
    25 Gachon University Gil Medical Center Incheon Korea, Republic of
    26 Samsung Medical Center Seoul Korea, Republic of
    27 Seoul National University Hospital Seoul Korea, Republic of
    28 Seoul St. Mary's Hospital Seoul Korea, Republic of
    29 Severance Hospital, Yonsei University Health System Seoul Korea, Republic of
    30 Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii Gdansk Poland
    31 Copernicus PL Sp. z o.o., Wojewodzkie Centrum Onkologii Gdańsk Poland
    32 Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach - Klinika Transplantacji Szpiku i Onkohematologii Gliwice Poland
    33 Szpital Uniwersytecki Krakow - Oddzial Kliniczny Hematologii Krakow Poland
    34 Pratia MCM Krakow Kraków Poland
    35 Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu Wroclaw Poland
    36 Hospital de Braga Braga Portugal
    37 Centro Hospitalar Universitario de Lisboa Norte - Hospital de Santa Maria Lisboa Portugal
    38 Champalimaud Cancer Center Lisbon Portugal
    39 Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE Porto Portugal
    40 Centro Hospitalar de Vila Nova de Gaia/Espinho EPE Vila Nova de Gaia Portugal
    41 Kantonsspital St. Gallen Saint Gallen Switzerland
    42 St James's University Hospital Leeds United Kingdom
    43 King's College Hospital London United Kingdom
    44 Royal Marsden Foundation Trust London United Kingdom
    45 University Hospital Southampton NHS Foundation Trust Southampton United Kingdom

    Sponsors and Collaborators

    • Kartos Therapeutics, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Kartos Therapeutics, Inc.
    ClinicalTrials.gov Identifier:
    NCT04502394
    Other Study ID Numbers:
    • KRT-232-111
    First Posted:
    Aug 6, 2020
    Last Update Posted:
    Aug 4, 2022
    Last Verified:
    Aug 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Kartos Therapeutics, Inc.
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 4, 2022