Clinical trial NCT04718675: A Study of KB-0742 in Participants With Relapsed or Refractory Solid Tumors Including Platinum Resistant High Grade Serous Ovarian Cancer (HGSOC)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
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
Lead sponsor: Kronos Bio
Sponsor class: INDUSTRY
First posted: 2021-01-22
Enrollment: 135
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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 \&lt;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

Primary outcomes:
measure: Part 1 and Part 2: Incidence of Adverse Events (AEs)
timeFrame: 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)
measure: Part 1 and Part 2: Number of Participants with Dose Limiting Toxicity (DLT) of KB-0742
timeFrame: Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 28 days
measure: Part 1: Maximally Tolerated Dose (MTD) of KB-0742
timeFrame: Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 28 days
measure: Part 1: Recommended Phase 2 Dose (RP2D) of KB-0742
timeFrame: Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 28 days
Secondary outcomes:
measure: Part 1: Maximal Plasma Concentration (Cmax) of KB-0742
timeFrame: Cycle 1 Day 1 through Cycle 6 Day 1, where a cycle is up to 28 days
measure: Part 1: Time to Maximal Plasma Concentration (Tmax) of KB-0742
timeFrame: Cycle 1 Day 1 through Cycle 6 Day 1, where a cycle is up to 28 days
measure: Part 1: Area Under The Plasma Concentration x Time Curve From Hour 0 to The Last Measurable Time Point (AUC0-last) of KB-0742
timeFrame: Cycle 1 Day 1 through Cycle 6 Day 1, where a cycle is up to 28 days
measure: Part 1 and Part 2: Progression Free Survival (PFS)
timeFrame: 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)
measure: Part 1 and Part 2: Disease Control Rate
timeFrame: 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)
measure: Part 1 and Part 2: Duration of Disease Control
timeFrame: 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)
measure: Part 1 and Part 2: Overall Response Rate (ORR)
timeFrame: 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)
measure: Part 1 and Part 2: Duration of Response (DOR)
timeFrame: 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)
measure: Part 2: Maximal Plasma Concentration (Cmax) of KB-0742
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 12, where a cycle is up to 28 days
measure: Part 2: Time to Maximal Plasma Concentration (Tmax) of KB-0742
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 12, where a cycle is up to 28 days
measure: Part 2: Trough Concentration (Ctrough) of KB-0742
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 12, where a cycle is up to 28 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: O'Neal Comprehensive Cancer Center at the University of Alabama
state: Alabama
city: Duarte
country: United States
facility: City of Hope
state: California
city: Fountain Valley
country: United States
facility: MemorialCare - Orange Coast Medical Center
state: California
city: Irvine
country: United States
facility: City of Hope - Orange County Lennar Foundation Cancer Center
state: California
city: Los Angeles
country: United States
facility: Precision NextGen Oncology
state: California
city: Los Angeles
country: United States
facility: Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles (UCLA)
state: California
city: Indianapolis
country: United States
facility: Community Health Network Community Cancer Center South
state: Indiana
city: Indianapolis
country: United States
facility: Community Health Network Community Cancer Center North
state: Indiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Rogel Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Cleveland
country: United States
facility: Cleveland Clinic - Taussig Cancer Center
state: Ohio
city: Gettysburg
country: United States
facility: Pennsylvania Cancer Specialists Research Institute - Gettysburg Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Nashville
country: United States
facility: SCRI Tennessee Oncology
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario Quirónsalud Madrid
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute London
Study officials:
References: