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A Dose Escalation and Cohort Expansion Study of KB-0742 in Participants With Relapsed or Refractory Solid Tumors or Non-Hodgkin Lymphoma

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ClinicalTrials.gov Identifier: NCT04718675
Recruitment Status : Recruiting
First Posted : January 22, 2021
Last Update Posted : February 15, 2023
Sponsor:
Information provided by (Responsible Party):
Kronos Bio

Study Description
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Brief Summary:

Part 1: Dose Escalation. The primary objective of Part 1 of this study is to evaluate the safety and tolerability of KB-0742 in participants with relapsed or refractory (R/R) solid tumors or non-Hodgkin lymphoma (NHL).

Part 2: Cohort Expansion. The primary objective of Part 2 of this study is to further evaluate the safety and tolerability of KB-0742 in defined participant cohorts.


Condition or disease Intervention/treatment Phase
Relapsed Solid Tumors Refractory Solid Tumors Non-Hodgkin Lymphoma Drug: KB-0742 Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1, First-in-human, Open-label Dose Escalation and Cohort Expansion Study of KB-0742 in Patients With Relapsed or Refractory Solid Tumors or Non-Hodgkin Lymphoma
Actual Study Start Date : February 8, 2021
Estimated Primary Completion Date : November 2023
Estimated Study Completion Date : March 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arms and Interventions
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Arm Intervention/treatment
Experimental: Part 1: Dose Escalation
Sequential cohorts of participants will receive escalating doses of KB-0742.
 Drug: KB-0742
Oral capsules
Experimental: Part 2: Cohort Expansion

Following identification of the maximally tolerated dose (MTD) / recommended Phase 2 dose (RP2D) in Part 1, the following expansion cohorts will be enrolled:

Cohort A: Relapsed or refractory (R/R) solid tumors with evidence of MYC amplication/overexpression.

Cohort B: Relapsed or refractory (R/R) small cell lung cancer (SCLC) and soft tissue sarcomas with evidence of transcription factor dysregulation.

 Drug: KB-0742
Oral capsules


Outcome Measures
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Primary Outcome Measures :
  1. Part 1 and Part 2: Incidence of Adverse Events (AEs) [ Time Frame: Cycle 1 Day 1 up to 30 days after the last dose, where each cycle is up to 28 days (up to approximately 38 months) ]
    Type, incidence, severity, causality and outcome of adverse events (AEs), including serious AEs and AEs at Grade 3 or above, based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0.

  2. Part 1 and Part 2: Number of Participants with Dose Limiting Toxicity (DLT) of KB-0742 [ Time Frame: Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 28 days ]
  3. Part 1: Maximally Tolerated Dose (MTD) of KB-0742 [ Time Frame: Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 28 days ]
  4. Part 1: Recommended Phase 2 Dose (RP2D) of KB-0742 [ Time Frame: Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 28 days ]

Secondary Outcome Measures :
  1. Part 1: Maximal Plasma Concentration (Cmax) of KB-0742 [ Time Frame: Cycle 1 Day 1 through Cycle 2 Day 1, where a cycle is up to 28 days ]
  2. Part 2: Maximal Plasma Concentration (Cmax) of KB-0742 [ Time Frame: Cycle 1 Day 1 and Cycle 1 Day 10, where a cycle is up to 28 days ]
  3. Part 1: Time to Maximal Plasma Concentration (Tmax) of KB-0742 [ Time Frame: Cycle 1 Day 1 through Cycle 2 Day 1, where a cycle is up to 28 days ]
  4. Part 2: Time to Maximal Plasma Concentration (Tmax) of KB-0742 [ Time Frame: Cycle 1 Day 1 and Cycle 1 Day 10, where a cycle is up to 28 days ]
  5. Part 1: Area Under The Plasma Concentration x Time Curve From Hour 0 to The Last Measurable Time Point (AUC0-last) of KB-0742 [ Time Frame: Cycle 1 Day 1 through Cycle 2 Day 1, where a cycle is up to 28 days ]
  6. Part 2: Trough Concentration (Ctrough) of KB-0742 [ Time Frame: Cycle 1 Day 1 and Cycle 1 Day 10, where a cycle is up to 28 days ]
  7. Part 1 and Part 2: Progression Free Survival (PFS) [ Time Frame: Cycle 1 Day 1 up to 30 days after the last dose, where each cycle is up to 28 days (up to approximately 38 months) ]
  8. Part 1 and Part 2: Disease Control Rate [ Time Frame: Cycle 1 Day 1 up to 30 days after the last dose, where each cycle is up to 28 days (up to approximately 38 months) ]
  9. Part 1 and Part 2: Duration of Disease Control [ Time Frame: Cycle 1 Day 1 up to 30 days after the last dose, where each cycle is up to 28 days (up to approximately 38 months) ]
  10. Part 1 and Part 2: Overall Response Rate (ORR) [ Time Frame: Cycle 1 Day 1 up to 30 days after the last dose, where each cycle is up to 28 days (up to approximately 38 months) ]
  11. Part 1 and Part 2: Duration of Response (DOR) [ Time Frame: Cycle 1 Day 1 up to 30 days after the last dose, where each cycle is up to 28 days (up to approximately 38 months) ]

Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males or females ≥ 18 years old (Parts 1 and 2A); males or females ≥ 16 years old (Part 2B)
  • Willing and able to provide consent (and assent for participants between the ages of 16-18)

  • Part 1: Participants who meet at least 1 of the following criteria:

    1. Any relapsed/refractory (R/R) solid tumor with readily accessible biopsy sites and consenting to 1 baseline and 1 on-treatment biopsy.

    2. Tumor type of interest (see list below) with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) AND at least 1 RECIST measurable scan prior to the most recent scan to document the rate of tumor growth before the initiation of study treatment. Tumor types of interest (R/R without other available therapeutic options) are:

      1. Small cell lung cancer (SCLC)
      2. Epithelial ovarian cancer or non-small cell lung cancer (NSCLC) with documented MYC copy number gain or overexpression as determined in a certified laboratory using a CAP/CLIA (or equivalent) assay or as assessed in a central laboratory designated by the sponsor
      3. Diffuse large B-cell lymphoma with documented MYC translocation or Burkitt's lymphoma (as determined by local testing)
      4. Sarcoma with documented transcription factor fusion (as determined by local testing)
      5. Chordoma, NUT midline carcinoma, or adenoid cystic carcinoma
  • Part 2A: Participants with histologically or cytologically confirmed solid tumors who have failed, are intolerant to or are considered ineligible for standard-of-care anti-cancer treatments.

Note: All Part 2, Cohort A, patients will require documented MYC copy number gain or overexpression as determined in a certified laboratory using a CAP/CLIA (or equivalent) assay or as assessed in a central laboratory designated by the sponsor. This cohort will include 7-10 patients with one of the following malignancies: NSCLC, triple-negative breast cancer, ovarian cancer, and lymphoma.

  • Part 2B: Histologically or cytologically confirmed SCLC or soft tissue sarcomas with defined transcription factor oncogenic drivers
  • Access to a tumor sample for central laboratory testing
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1
  • Evaluable or measurable disease, per RECIST 1.1 for solid tumors or the Lugano Classification for non-Hodgkin lymphoma
  • Adequate bone marrow and organ function
  • Recovery from treatment-related toxicities from prior therapies to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade ≤ 1 or to baseline level
  • Must agree to use highly effective birth control during the trial and for at least 3 months after the last dose of study drug; female participants cannot be pregnant or breastfeeding

Exclusion Criteria:

  • Any other anti-cancer therapies including chemotherapy, immunotherapy, or hormonal therapy within 4 weeks or 5 half-lives (whichever is shorter)
  • History of surgery (except for diagnostic purposes) or non-palliative radiotherapy within 4 weeks
  • History of allogeneic transplantation within 6 months
  • Active central nervous system (CNS) involvement by the underlying malignancy; previously treated CNS metastatic disease is permitted with magnetic resonance imaging (MRI) documentation of stable disease for at least 3 months prior to study start
  • History of stroke or intracranial hemorrhage within ≤6 months
  • History of seizure disorder, ie, recurrent seizures with an underlying etiology and requiring ongoing anti-epileptic medication
  • Current use of medications associated with seizure risk unless approved by Medical Monitor
  • Active infections requiring systemic antibiotic, antiviral or antifungal therapy
  • Known active coronavirus disease 2019 (COVID-19)
  • Clinically significant heart disease
  • Uncontrolled hypertension
  • Prolongation of QT interval at baseline
  • Known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection
  • Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04718675


Contacts
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Contact: Director of Clinical Operations 650-484-1583 clinicaltrials@kronosbio.com

Locations
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United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Dr. Villalona, MD         
City of Hope - Orange County Lennar Foundation Cancer Center Recruiting
Irvine, California, United States, 92618
Contact: Dr. Villalona, MD         
Cedars Sinai Recruiting
Los Angeles, California, United States, 90048
Contact: Dr. Mita    800-233-2771      
University of California, Los Angeles (UCLA) Recruiting
Los Angeles, California, United States, 90095
Contact: Noah Federman, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Dr. Gregory Cote         
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Jia Luo, MD         
United States, Missouri
Washington University Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Dr. Van Tine         
United States, Tennessee
SCRI Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Mary Crowley Cancer Research Withdrawn
Dallas, Texas, United States, 75230
South Texas Accelerated Research Therapeutics Recruiting
San Antonio, Texas, United States, 78229
Contact: Isabel Jimenez, RN, MSN    210-593-5265    isabel.jimenez@startsa.com   
Sponsors and Collaborators
Kronos Bio
More Information
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Responsible Party: Kronos Bio
ClinicalTrials.gov Identifier: NCT04718675    
Other Study ID Numbers: KB-0742-1001
First Posted: January 22, 2021    Key Record Dates
Last Update Posted: February 15, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kronos Bio:
KB-0742
Relapsed Solid Tumors
Refractory Solid Tumors
Non-Hodgkin Lymphoma
CDK9 Inhibitor
Additional relevant MeSH terms:
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Lymphoma
Neoplasms
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
 Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases