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

NCT04718675 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: KB-0742-10012023-503739-16-00
• Study Type: interventional
• Target: 135
• Locations: 3 countries
• Sites: 24

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

Conditions

Relapsed Solid Tumors; Refractory Solid Tumors; Non-Hodgkin Lymphoma; HGSOC; Platinum Resistant High Grade Serous Ovarian Cancer

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

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (11)

• 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 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 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 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)

Study Arms (2)

Part 1: Dose Escalation

EXPERIMENTAL

Sequential cohorts of participants will receive escalating doses of KB-0742.

Drug: KB-0742

Part 2: Cohort Expansion

EXPERIMENTAL

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 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.

Drug: KB-0742

Interventions

KB-0742 DRUG

Oral capsules

Part 1: Dose Escalation; Part 2: Cohort Expansion

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Kronos Bio: lead

Study Sites (24)

O'Neal Comprehensive Cancer Center at the University of Alabama

Birmingham, Alabama, 35233, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

MemorialCare - Orange Coast Medical Center

Fountain Valley, California, 92708, United States

Location

City of Hope - Orange County Lennar Foundation Cancer Center

Irvine, California, 92618, United States

Location

Precision NextGen Oncology

Los Angeles, California, 90025, United States

Location

Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of California, Los Angeles (UCLA)

Los Angeles, California, 90095, United States

Location

Community Health Network Community Cancer Center South

Indianapolis, Indiana, 46227, United States

Location

Community Health Network Community Cancer Center North

Indianapolis, Indiana, 46250, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Cleveland Clinic - Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Pennsylvania Cancer Specialists Research Institute - Gettysburg Cancer Center

Gettysburg, Pennsylvania, 17325, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

SCRI Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario Quirónsalud Madrid

Madrid, 28223, Spain

Location

Sarah Cannon Research Institute London

London, W1G 6AD, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2021
• First Posted: January 22, 2021
• Study Start: February 8, 2021
• Primary Completion: January 7, 2025
• Study Completion: February 7, 2025
• Last Updated: February 17, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

ES (3); US (20); GB (1)