NCT04718675终止1 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Kronos Bio
- 入组人数
- 135
- 试验地点
- 24
- 主要终点
- Part 1 and Part 2: Incidence of Adverse Events (AEs)
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •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
排除标准
- •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
研究组 & 干预措施
Part 1: Dose Escalation
Experimental
Sequential cohorts of participants will receive escalating doses of KB-0742.
干预措施: KB-0742 (Drug)
Part 2: Cohort Expansion
Experimental
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.
干预措施: KB-0742 (Drug)
结局指标
主要结局
Part 1 and Part 2: Incidence of Adverse Events (AEs)
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: Cycle 1 Day 1 through Cycle 2 Day 1, where each cycle is up to 28 days
次要结局
- 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)
- 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)
- 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)
- 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))
- 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))
- 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))
- 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))
- 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))
- 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)
- 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)
- 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)
研究者
研究点 (24)
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