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Relapsed Solid TumorsPhase 1/2NCT04718675

A Study of KB-0742 in Participants With Relapsed or Refractory Solid Tumors Including Platinum Resistant High Grade Serous Ovarian Cancer (HGSOC)

A Phase 1/2 study testing KB-0742 in people with Relapsed Solid Tumors and Refractory Solid Tumors, run by Kronos Bio at 24 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 12 years and older
What is being tested?
KB-0742
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
135 participants
Where
24 sitesin 3 countries
Study dates
8 Feb 2021to 7 Feb 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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:
  • 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.
  • 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:
  • SCLC
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  • Epithelial ovarian cancer, TNBC, or NSCLC
  • Other epithelial solid tumor with evidence of MYC copy number gain based on local testing
  • Diffuse large B-cell lymphoma with documented MYC translocation or Burkitt's lymphoma (as determined by local testing)
  • 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
  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

24 sites in 3 countries.

24 sites in 3 countries

United States20 sites
  • University of Michigan Rogel Cancer Center

    Ann Arbor, Michigan, 48109

  • O'Neal Comprehensive Cancer Center at the University of Alabama

    Birmingham, Alabama, 35233

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Cleveland Clinic - Taussig Cancer Center

    Cleveland, Ohio, 44195

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • City of Hope

    Duarte, California, 91010

  • Virginia Cancer Specialists

    Fairfax, Virginia, 22031

  • MemorialCare - Orange Coast Medical Center

    Fountain Valley, California, 92708

  • Pennsylvania Cancer Specialists Research Institute - Gettysburg Cancer Center

    Gettysburg, Pennsylvania, 17325

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Community Health Network Community Cancer Center South

    Indianapolis, Indiana, 46227

  • Community Health Network Community Cancer Center North

    Indianapolis, Indiana, 46250

  • City of Hope - Orange County Lennar Foundation Cancer Center

    Irvine, California, 92618

  • Precision NextGen Oncology

    Los Angeles, California, 90025

  • Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • University of California, Los Angeles (UCLA)

    Los Angeles, California, 90095

  • SCRI Tennessee Oncology

    Nashville, Tennessee, 37203

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

  • Washington University

    St Louis, Missouri, 63110

Other trials in United States

Spain3 sites
  • Hospital Clinic de Barcelona

    Barcelona, 08036

  • Hospital Clínico San Carlos

    Madrid, 28040

  • Hospital Universitario Quirónsalud Madrid

    Madrid, 28223

Other trials in Spain

United Kingdom1 site
  • Sarah Cannon Research Institute London

    London, W1G 6AD

Other trials in United Kingdom

About this study

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

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 including Platinum Resistant High Grade Serous Ovarian Cancer (HGSOC).

Read the detailed description

Part 2 cohort expansion is now enrolling Platinum Resistant High Grade Serous Ovarian Cancer (HGSOC) patients who may have one or more of these genetic alterations, BRCA 1 mutation, BRCA 2 mutation, MYC amplification/ overexpression, Homologous Recombination Deficient (HRD) positive.

Being tested
KB-0742
Keywords
KB-0742, Relapsed Solid Tumors, Refractory Solid Tumors, Non-Hodgkin Lymphoma, CDK9 Inhibitor, Platinum Resistant High Grade Serous Ovarian Cancer, HGSOC, BRCA1 mutation, BRCA2 mutation, HRD positive, MYC amplification/overexpression
Medical subject headings
Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • KB-0742Drug

    Oral capsules

Study groups in NCT04718675
Study groupRoleWhat they receive
Part 1: Dose EscalationExperimentalSequential cohorts of participants will receive escalating doses of KB-0742.
Receives: Drug: KB-0742
Part 2: Cohort ExpansionExperimentalFollowing 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 high grade serous 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.
Receives: Drug: KB-0742

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 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)

  2. Part 1 and Part 2: Number of Participants with Dose Limiting Toxicity (DLT) of KB-0742

    Measured: 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

    Measured: 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

    Measured: Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 28 days

Secondary outcomes (11)
  1. Part 1: Maximal Plasma Concentration (Cmax) of KB-0742

    Measured: Cycle 1 Day 1 through Cycle 6 Day 1, where a cycle is up to 28 days

  2. Part 1: Time to Maximal Plasma Concentration (Tmax) of KB-0742

    Measured: Cycle 1 Day 1 through Cycle 6 Day 1, where a cycle is up to 28 days

  3. Part 1: Area Under The Plasma Concentration x Time Curve From Hour 0 to The Last Measurable Time Point (AUC0-last) of KB-0742

    Measured: Cycle 1 Day 1 through Cycle 6 Day 1, where a cycle is up to 28 days

  4. Part 1 and Part 2: Progression Free Survival (PFS)

    Measured: 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)

  5. Part 1 and Part 2: Disease Control Rate

    Measured: 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)

  6. Part 1 and Part 2: Duration of Disease Control

    Measured: 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)

  7. Part 1 and Part 2: Overall Response Rate (ORR)

    Measured: 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: Duration of Response (DOR)

    Measured: 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 2: Maximal Plasma Concentration (Cmax) of KB-0742

    Measured: Cycle 1 Day 1 and Cycle 1 Day 12, where a cycle is up to 28 days

  10. Part 2: Time to Maximal Plasma Concentration (Tmax) of KB-0742

    Measured: Cycle 1 Day 1 and Cycle 1 Day 12, where a cycle is up to 28 days

  11. Part 2: Trough Concentration (Ctrough) of KB-0742

    Measured: Cycle 1 Day 1 and Cycle 1 Day 12, where a cycle is up to 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jan 2021
  2. Study start8 Feb 2021
  3. Primary completion7 Jan 2025
  4. Study completion7 Feb 2025

Why it stopped: Due to lack of safety and futility

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
135 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04718675
Sponsor's protocol ID
KB-0742-1001
Other IDs
2023-503739-16-00, 2023
Status last verified
Nov 2024
First submitted
18 Jan 2021
Last updated
17 Feb 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing KB-0742 in people with Relapsed Solid Tumors and Refractory Solid Tumors, run by Kronos Bio at 24 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States, Spain, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Due to lack of safety and futility). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2025.

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