A Dose Escalation and Cohort Expansion Study of KB-0742 in Participants With Relapsed or Refractory Solid Tumors or Non-Hodgkin Lymphoma
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ClinicalTrials.gov Identifier: NCT04718675 |
Recruitment Status :
Recruiting
First Posted : January 22, 2021
Last Update Posted : February 2, 2024
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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.
Condition or disease | Intervention/treatment | Phase |
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Relapsed Solid Tumors Refractory Solid Tumors Non-Hodgkin Lymphoma | Drug: KB-0742 | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 280 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Actual Study Start Date : | February 8, 2021 |
Estimated Primary Completion Date : | December 2025 |
Estimated Study Completion Date : | December 2025 |
Arm | Intervention/treatment |
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Experimental: Part 1: Dose Escalation
Sequential cohorts of participants will receive escalating doses of KB-0742.
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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 |
- 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) ]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.
- Part 1 and Part 2: Number of Participants with Dose Limiting Toxicity (DLT) of KB-0742 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 28 days ]
- Part 1: Maximal Plasma Concentration (Cmax) of KB-0742 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Cycle 1 Day 1 and Cycle 1 Day 12, where a cycle is up to 28 days ]
- Part 1 and Part 2: Progression Free Survival (PFS) [ 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) ]
- Part 1 and Part 2: Disease Control Rate [ 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) ]
- Part 1 and Part 2: Duration of Disease Control [ 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) ]
- Part 1 and Part 2: Overall Response Rate (ORR) [ 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) ]
- Part 1 and Part 2: Duration of Response (DOR) [ 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) ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 12 Years and older (Child, Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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)
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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.
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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
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04718675
Contact: Director of Clinical Operations | 650-781-5200 | clinicaltrials@kronosbio.com |
Responsible Party: | Kronos Bio |
ClinicalTrials.gov Identifier: | NCT04718675 |
Other Study ID Numbers: |
KB-0742-1001 2023-503739-16-00 ( Other Identifier: EU CT Number ) |
First Posted: | January 22, 2021 Key Record Dates |
Last Update Posted: | February 2, 2024 |
Last Verified: | January 2024 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
KB-0742 Relapsed Solid Tumors Refractory Solid Tumors Non-Hodgkin Lymphoma CDK9 Inhibitor |
Lymphoma Neoplasms Lymphoma, Non-Hodgkin Neoplasms by Histologic Type |
Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases |