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

Non-Hodgkin Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04718675
• Other study ID #: KB-0742-1001
• Secondary ID: 2023-503739-16-0
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 8, 2021
• Est. completion date: December 2025

Study information

• Verified date: January 2024
• Source: Kronos Bio
• Contact: Director of Clinical Operations
• Phone: 650-781-5200
• Email: clinicaltrials[@]kronosbio.com
• Is FDA regulated: No
• Study type: Interventional

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 280
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Neoplasms
• Non-Hodgkin Lymphoma
• Refractory Solid Tumors
• Relapsed Solid Tumors

Intervention

Drug:
• KB-0742
Oral capsules

Locations

Country	Name	City	State
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital Universitario Quirónsalud Madrid	Madrid
United Kingdom	Sarah Cannon Research Institute London	London
United States	University of Michigan Rogel Cancer Center	Ann Arbor	Michigan
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Cleveland Clinic - Taussig Cancer Center	Cleveland	Ohio
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	MemorialCare - Orange Coast Medical Center	Fountain Valley	California
United States	Pennsylvania Cancer Specialists Research Institute - Gettysburg Cancer Center	Gettysburg	Pennsylvania
United States	Oncology Consultants Texas Medical Center	Houston	Texas
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Community Health Network Community Cancer Center North	Indianapolis	Indiana
United States	Community Health Network Community Cancer Center South	Indianapolis	Indiana
United States	City of Hope - Orange County Lennar Foundation Cancer Center	Irvine	California
United States	Cedars Sinai	Los Angeles	California
United States	Norris Comprehensive Cancer Center	Los Angeles	California
United States	Precision NextGen Oncology	Los Angeles	California
United States	University of California, Los Angeles (UCLA)	Los Angeles	California
United States	SCRI Tennessee Oncology	Nashville	Tennessee
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Washington University	Saint Louis	Missouri
United States	South Texas Accelerated Research Therapeutics	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Kronos Bio

Countries where clinical trial is conducted

United States,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)