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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Non-Hodgkin Lymphoma; Refractory Solid Tumors; Relapsed Solid Tumors
• Intervention / Treatment: Drug: KB-0742

• Study Type: Interventional
• Enrollment (Estimated): 280
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Director of Clinical Operations; Phone Number: 650-781-5200; Email: clinicaltrials@kronosbio.com

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clinic de Barcelona
    • Contact: Ivan Victoria Ruiz, MD
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Clinico San Carlos
    • Contact: Aranzazu Manzano Fernandez, MD
  • Madrid, Spain, 28223
    • Recruiting
    • Hospital Universitario Quirónsalud Madrid
    • Contact: Valentina Boni, MD
• United Kingdom
  • London, United Kingdom, W1G 6AD
    • Recruiting
    • Sarah Cannon Research Institute London
    • Contact: Elisa Fontana, MD
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope
      • Contact: Dr. Villalona, MD
    • Fountain Valley, California, United States, 92708
      • Recruiting
      • MemorialCare - Orange Coast Medical Center
      • Contact: Amol Rao, MD
    • Irvine, California, United States, 92618
      • Recruiting
      • City of Hope - Orange County Lennar Foundation Cancer Center
      • Contact: Dr. Villalona, MD
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars Sinai
      • Contact: Dr. Mita; Phone Number: 800-233-2771
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California, Los Angeles (UCLA)
      • Contact: Noah Federman, MD
    • Los Angeles, California, United States, 90033
      • Recruiting
      • Norris Comprehensive Cancer Center
      • Contact: Jacob Thomas, MD
    • Los Angeles, California, United States, 90025
      • Recruiting
      • Precision NextGen Oncology
      • Contact: Kamalesh Sankhala, MD
  • Indiana
    • Indianapolis, Indiana, United States, 46227
      • Recruiting
      • Community Health Network Community Cancer Center South
      • Contact: Dr. Natraj Reddy Ammakkanavar, MD
    • Indianapolis, Indiana, United States, 46250
      • Recruiting
      • Community Health Network Community Cancer Center North
      • Contact: Dr Natraj Reddy Ammakkanavar, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Dr. Gregory Cote
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Dana Farber Cancer Institute
      • Contact: Jia Luo, MD
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan Rogel Cancer Center
      • Contact: Rashmi Chugh, MD
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Barbara Ann Karmanos Cancer Institute
      • Contact: Tarik Hadid, MD
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University
      • Contact: Dr. Van Tine
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic - Taussig Cancer Center
      • Contact: Alex Adjei, MD
  • Pennsylvania
    • Gettysburg, Pennsylvania, United States, 17325
      • Recruiting
      • Pennsylvania Cancer Specialists Research Institute - Gettysburg Cancer Center
      • Contact: Satish Shah, MD
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • SCRI Tennessee Oncology
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center
      • Contact: Anthony Conley, MD
    • Houston, Texas, United States, 77024
      • Recruiting
      • Oncology Consultants Texas Medical Center
      • Contact: Mahran Shoukier, MD
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • South Texas Accelerated Research Therapeutics
      • Contact: Isabel Jimenez, RN, MSN; Phone Number: 210-593-5265; Email: isabel.jimenez@startsa.com
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialists
      • Contact: Mohamad Adham Salkeni, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Males or females ≥ 18 years old (Parts 1 and 2A); males or females ≥ 12 years old and with a body weight ≥ 40 kg are eligible to enroll with tumor types including soft-tissue sarcomas, Ewing's sarcoma, alveolar rhabdomyosarcoma, NUT midline carcinoma (NMC), or chordoma (Part 2B)
• Willing and able to provide consent (and assent for participants between the ages of 12 to <18)

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

  1. Any R/R solid tumor with, in the opinion of the investigator at the time of screening has at least 1 readily accessible biopsy site(s) and who consents to 1 baseline and 1 on-treatment biopsy. If the feasibility of obtaining biopsies changes after the participant has been consented due to changes in clinical or surgical considerations and the participant otherwise meets all eligibility criteria, they may still enroll/or continue on study.

  2. Tumor type of interest (see list below) with measurable disease per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST) 1.1 or Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST) 1.0 for solid tumors or by Lugano Classification or Modified Weighted Assessment Tool (mSWAT) for NHL AND at least 1 measurable scan per one of the above criteria 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. SCLC
     2. Epithelial ovarian cancer, TNBC, or NSCLC
     3. Other epithelial solid tumor with evidence of MYC copy number gain based on local testing
     4. Diffuse large B-cell lymphoma with documented MYC translocation or Burkitt's lymphoma (as determined by local testing)
     5. Sarcoma of histologic subtypes known to be associated with transcription factor fusion, specifically: i. Myxoid/round cell sarcoma ii. Clear cell sarcoma iii. Desmoplastic small round cell tumor iv. Low grade fibromyxoid sarcoma v. Extraskeletal myxoid chondrosarcoma vi. Ewing sarcoma vii. Alveolar rhabdomyosarcoma
     6. Chordoma, NUT midline carcinoma, or adenoid cystic carcinoma
• Part 2, Cohort A: 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: Part 2, Cohort A, will include participants with relapsed or refractory solid tumors including NSCLC, TNBC and ovarian cancer.
• Part 2, Cohort B: Participants with histologically or cytologically confirmed tumor type of interest without access to or intolerant of other approved therapies, including SCLC.
• For both Parts 1 and 2:
• 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 or PERCIST 1.0 for solid tumors or the Lugano Classification or mSWAT for NHL
• 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. Participants with SCLC with prior treatment with stereotactic radiosurgery or whole brain radiation therapy for CNS metastatic disease 2 weeks or more before study start may be considered eligible for enrollment if assessed stable and meet all other eligibility criteria.
• History of stroke or intracranial hemorrhage within ≤6 months
• History of seizure or seizure disorder, ie, recurrent seizures with an underlying etiology and requiring ongoing anti-epileptic medication
• Current use of medications associated with seizure risk
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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 contingent recommended Phase 2 dose (RP2D) in Part 1, the following expansion cohorts will be enrolled: Cohort A: Participants with R/R non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), and ovarian cancer. Cohort B: Participants with R/R small cell lung cancer (SCLC), NUT midline carcinomas (NMC), adenoid cystic carcinoma (ACC), chordoma and soft tissue sarcomas associated with transcription factor fusion.	Drug: KB-0742; Oral capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 and Part 2: Incidence of Adverse Events (AEs)	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.	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)
Part 1 and Part 2: Number of Participants with Dose Limiting Toxicity (DLT) of KB-0742		Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 28 days
Part 1: Maximally Tolerated Dose (MTD) of KB-0742		Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 28 days
Part 1: Recommended Phase 2 Dose (RP2D) of KB-0742		Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Part 1 and Part 2: Progression Free Survival (PFS)	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)
Part 1 and Part 2: Disease Control Rate	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)
Part 1 and Part 2: Duration of Disease Control	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)
Part 1 and Part 2: Overall Response Rate (ORR)	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)
Part 1 and Part 2: Duration of Response (DOR)	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)
Part 1: Maximal Plasma Concentration (Cmax) of KB-0742	Cycle 1 Day 1 through Cycle 6 Day 1, where a cycle is up to 28 days
Part 2: Maximal Plasma Concentration (Cmax) of KB-0742	Cycle 1 Day 1 and Cycle 1 Day 12, where a cycle is up to 28 days
Part 1: Time to Maximal Plasma Concentration (Tmax) of KB-0742	Cycle 1 Day 1 through Cycle 6 Day 1, where a cycle is up to 28 days
Part 2: Time to Maximal Plasma Concentration (Tmax) of KB-0742	Cycle 1 Day 1 and Cycle 1 Day 12, where a cycle is up to 28 days
Part 1: Area Under The Plasma Concentration x Time Curve From Hour 0 to The Last Measurable Time Point (AUC0-last) of KB-0742	Cycle 1 Day 1 through Cycle 6 Day 1, where a cycle is up to 28 days
Part 2: Trough Concentration (Ctrough) of KB-0742	Cycle 1 Day 1 and Cycle 1 Day 12, where a cycle is up to 28 days

Collaborators and Investigators

• Sponsor: Kronos Bio

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2021
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: January 18, 2021
• First Submitted That Met QC Criteria: January 18, 2021
• First Posted (Actual): January 22, 2021

Study Record Updates

• Last Update Posted (Estimated): February 2, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Non-Hodgkin Lymphoma; Refractory Solid Tumors; CDK9 Inhibitor; Relapsed Solid Tumors; KB-0742
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms; Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: KB-0742-1001; 2023-503739-16-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No