Phase I/II, 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
Study Identifier:
KB-0742-1001
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
Terminated/Withdrawn
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Study Summary
To establish the dose, safety and efficacy, pharmacokinetic (PK) and pharmacodynamic profile of KB-0742 in patients with MYC-amplified advanced solid tumors.
To define a pharmacologically active dose and schedule which affords appropriate target engagement and acceptable safety, setting the stage for potential further development of this promising investigational therapy.
Primary objectives include evaluation of pharmacokinetics (PK), pharmacodynamics (PD), safety, tolerability, preliminary anti-tumor activity, and identifying a
maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). PK measurements include Cmax, tmax, AUC0-last, accumulation ratio (Racc) and t1/2. Safety data will be evaluated per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE) v5.0.
To evaluate phosphorylation of the CDK9 substrate serine 2 on the RNA Polymerase II C-terminal domain (pSER2) and CDK9-responsive gene expression.
To assess every other cycle starting from cycle two after treatment using RECIST 1.1 criteria.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
I/II
Sex
Female & Male
Age
12+ years
Study Drug
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Study Status
Indicates the current recruitment status or the expanded access status
Terminated/Withdrawn
Requirements information
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:
- 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
- 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
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START San Antonio
San Antonio, TX, United States, 78229
Investigator
Drew Rasco
Status
Recruitment Complete
Condition(s) Treated at Site
Breast Cancers
Non-Small Cell Lung Cancer
Ovarian
Small Cell Lung
Head & Neck
Solid Tumor
Soft Tissue Sarcoma
Lymphoma, Non-Hodgkin's
Neuroendocrine