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

NCT ID: NCT04718675

Last Updated: 2025-02-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 135 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-08
• Study Completion Date: 2025-02-07

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).

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Dose Escalation

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

Group Type: EXPERIMENTAL

KB-0742

Intervention Type: DRUG

Oral capsules

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 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.

Group Type: EXPERIMENTAL

KB-0742

Intervention Type: DRUG

Oral capsules

Interventions

KB-0742

Oral capsules

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kronos Bio

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

O'Neal Comprehensive Cancer Center at the University of Alabama

Birmingham, Alabama, United States

City of Hope

Duarte, California, United States

MemorialCare - Orange Coast Medical Center

Fountain Valley, California, United States

City of Hope - Orange County Lennar Foundation Cancer Center

Irvine, California, United States

Precision NextGen Oncology

Los Angeles, California, United States

Norris Comprehensive Cancer Center

Los Angeles, California, United States

University of California, Los Angeles (UCLA)

Los Angeles, California, United States

Community Health Network Community Cancer Center South

Indianapolis, Indiana, United States

Community Health Network Community Cancer Center North

Indianapolis, Indiana, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Washington University

St Louis, Missouri, United States

Cleveland Clinic - Taussig Cancer Center

Cleveland, Ohio, United States

Pennsylvania Cancer Specialists Research Institute - Gettysburg Cancer Center

Gettysburg, Pennsylvania, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

SCRI Tennessee Oncology

Nashville, Tennessee, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Virginia Cancer Specialists

Fairfax, Virginia, United States

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital Clínico San Carlos

Madrid, , Spain

Hospital Universitario Quirónsalud Madrid

Madrid, , Spain

Sarah Cannon Research Institute London

London, , United Kingdom

Countries

United States; Spain; United Kingdom

Other Identifiers

2023-503739-16-00

Identifier Type: OTHER

Identifier Source: secondary_id

KB-0742-1001

Identifier Type: -

Identifier Source: org_study_id