A Phase 1/2 Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of SNDX-5613 in Patients With Colorectal Cancer and Other Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 41
- 试验地点
- 6
- 主要终点
- Phase 1a: Number of Participants Experiencing Dose Limiting Toxicities
研究概览
简要总结
This study will evaluate the safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of revumenib in participants with colorectal cancer (CRC) or other solid tumors who have failed at least 1 prior line of therapy.
详细描述
The study will be conducted in two parts. The Phase 1 portion of the study consists of a dose escalation cohort, and a signal-seeking expansion where anti-tumor activity signals will be evaluated. The Phase 2 portion of the study will further confirm the anti-tumor activity signals of revumenib.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female participants aged ≥18 years
- •Participants with metastatic CRC or other solid tumors
- •Evidence of locally recurrent or metastatic disease based on imaging studies within 28 days of cycle 1/day 1 (C1D1)
- •CRC participants must have had at least one line of standard-of-care therapy and must have progressed on or been intolerant to, or unable to receive, oxaliplatin, irinotecan, and bevacizumab in the advanced/metastatic setting.
- •Other solid tumor participants must have had all approved standard therapies that are available to the participant, unless contraindicated or intolerable.
- •Participants must have experienced documented unequivocal progressive disease by either RECIST v1.1 or clinical assessment, or experienced unacceptable toxicity with their prior therapy.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1
- •If receiving radiation therapy, has had a 2-week washout period following completion of the treatment prior to receiving the C1D1 dose and continues to have at least 1 measurable lesion
- •At least 42 days since prior immunotherapy, including tumor vaccines and checkpoint inhibitors, and at least 21 days since receipt of chimeric antigen receptor therapy or other modified T-cell therapy
- •Adequate bone marrow, renal, cardiac, and liver function
排除标准
- •Participant has a prior history of malignant bowel obstruction requiring hospitalization in the 6 months prior to enrollment
- •Participant has a history of uncontrolled ascites, defined as symptomatic ascites and/or repeated paracenteses for symptom control in the past 3 months
- •Detectable human immunodeficiency virus (HIV) viral load within the previous 6 months. Participants with a known history of HIV 1/2 antibodies must have viral load testing prior to study enrollment
- •Hepatitis B and/or C
- •Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class ≥II), life-threatening, uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack
- •Corrected QT interval (QTc) >450 milliseconds
- •Any gastrointestinal (GI) issue of the upper GI tract likely to affect oral drug absorption or ingestion (for example, gastric bypass, gastroparesis)
- •Cirrhosis with a Child-Pugh score of B or C
- •Brain metastasis except for those participants who have completed definitive therapy, are not on steroids, have a stable neurologic status for at least 4 weeks after completion of the definitive therapy and steroids, and do not have neurologic dysfunction that would confound the evaluation of neurologic and other adverse events (AEs)
- •History of or any concurrent condition, therapy, laboratory abnormality, or allergy to excipients that in the Investigator's opinion might confound the results of the study, interfere with the participant's ability to participate for the full duration of the study, or not be in the best interest of the participant to participate
- •Participant has received prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study baseline or who has not recovered (that is, ≤Grade 1 or at baseline) from AEs related to a previously administered agent.
- •Participation in another therapeutic interventional clinical study in which an investigational agent was administered within 30 days before starting revumenib
- •Participant has received a transfusion of blood products or administration of colony stimulating factors within 4 weeks of the first dose of the study drug
- •History of additional malignancy within the prior 5 years, excluding adequately treated basal cell carcinoma, squamous cell of the skin, cervical intraepithelial neoplasia/cervical carcinoma in situ, or melanoma in situ or ductal carcinoma in situ of the breast
研究组 & 干预措施
Phase 2: Revumenib
Participants will receive revumenib tablets TID or BID from Day 1 of each 28-day cycle.
干预措施: Revumenib (Drug)
Phase 2: Chemotherapy
Participants will receive chemotherapy from Day 1 of each 28-day cycle.
干预措施: Chemotherapy (Drug)
Phase 1a: Dose Escalation
Participants will receive revumenib tablets or capsules three times a day (TID) or two times a day (BID) from Day 1 of each 28-day cycle.
干预措施: Revumenib (Drug)
Phase 1b: Signal-Seeking
Participants will receive revumenib tablets TID or BID from Day 1 of each 28-day cycle.
干预措施: Revumenib (Drug)
结局指标
主要结局
Phase 1a: Number of Participants Experiencing Dose Limiting Toxicities
时间窗: Up to Day 29
Phase 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
时间窗: Approximately 12 months
Phase 1b: Disease Control Rate (DCR)
时间窗: Approximately 6 months
Phase 1b: Overall Response Rate (ORR)
时间窗: Approximately 6 months
Phase 2: Progression Free Survival (PFS)
时间窗: Approximately 4 months
Phase 1a: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)
时间窗: Day 1 up to Day 28
DLT was defined as any of the following occurring in Cycle 1: Grade 4 neutropenia (absolute neutrophil count \[ANC\] \<500 cells/mm\^3) unresolved to Grade 2 (ANC \>1500 cells/mm\^3) or baseline for more than 7 consecutive days in the absence of growth factor support, ≥Grade 3 neutropenia (ANC \<1000 cells/mm\^3) with a single temperature of \>38.3°Celsius (101°Fahrenheit) or a sustained temperature of ≥38°Celsius (100.4°Fahrenheit) for more than 1 hour, Grade 4 thrombocytopenia (\<25,000/mm\^3) of any duration, ≥Grade 3 thrombocytopenia (\<50,000/mm\^3) with clinically significant bleeding, Grade 4 anemia (i.e, life-threatening consequences; urgent intervention indicated) or ≥Grade 3 nonhematologic toxicity as defined in Common Terminology Criteria for Adverse Events version 5.0 scale where Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, medically significant, Grade 4=Life-threatening and 5=Death.
Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to 2.2 years
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE was therefore any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of the study intervention, whether or not considered related to the study intervention. TEAEs were defined as those having an onset on or after the first dose of revumenib or a sign, symptom, or a diagnosis that worsened on or after first dose of revumenib but no later than 30 days after the date of the last dose of revumenib. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Phase 1: Disease Control Rate (DCR)
时间窗: Up to 2.2 years
DCR was defined as the percentage of participants with objective evidence of confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) according to Response Evaluation in Solid Tumors (RECIST) version 1.1 criteria as assessed by the investigator. CR=disappearance of all target lesions; disappearance of non-target lesions. PR=At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. PD=At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions.
Phase 1: Overall Response Rate (ORR)
时间窗: Up to 2.2 years
ORR was defined as the percentage of participants who achieved a best overall response of PR or CR according to RECIST v1.1 criteria as assessed by the investigator. PR=At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. CR=Disappearance of all target lesions; disappearance of all nontarget lesions.
Phase 2: Progression Free Survival (PFS)
时间窗: Up to 2.2 years
PFS was defined as the time from the first dosing date to the first documented progression or death due to any cause, whichever occurred first.
次要结局
- Phase 2: Tmax of Revumenib(Predose up to approximately 6 months)
- Phase 2: Duration of Response (DOR) as Assessed by Blinded Radiographic Review(Approximately 3 years)
- Phase 1: Maximum Plasma Concentration (Cmax) of Revumenib(Predose up to approximately 12 months)
- Phase 2: Overall Survival (OS)(Approximately 5 years)
- Phase 2: DCR at 6 Cycles (28-Day Cycles) as Assessed by Blinded Radiographic Review(Approximately 6 months)
- Phase 2: ORR as Assessed by Blinded Radiographic Review Using Response Evaluation Criteria in Solid Tumors (RECIST), version (v)1.1(Approximately 6 months)
- Phase 2: DCR at 6 Cycles (28-Day Cycles) as Assessed by the Investigator(Approximately 6 months)
- Phase 2: ORR as Assessed by the Investigator per RECIST v1.1(Approximately 6 months)
- Phase 1: Time to Maximum Plasma Concentration (Tmax) of Revumenib(Predose up to approximately 12 months)
- Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Revumenib(Predose up to approximately 12 months)
- Phase 2: AUC of Revumenib(Predose up to approximately 6 months)
- Phase 2: Cmax of Revumenib(Predose up to approximately 6 months)
- Phase 2: Number of Participants Experiencing TEAEs(Approximately 3 years)
- Phase 2: DOR as Assessed by the Investigator(Approximately 3 years)
- Phase 1a: Maximum Plasma Concentration (Cmax) of Revumenib(Cycle 1 Day 7, Cycle 1 Day 14, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 5 Day 1 (Cycle length=28 days))
- Phase 1b: Maximum Plasma Concentration (Cmax) of Revumenib(Cycle 1 Day 7, Cycle 1 Day 14, Cycle 2 Day 8, Cycle 2 Day 15 (Cycle length=28 days))
- Phase 1a: Area Under the Plasma Concentration Versus Time Curve (AUC0-t) of Revumenib(Cycle 1 Day 7, Cycle 1 Day 14, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 5 Day 1 (Cycle length=28 days))
- Phase 1a: Time to Maximum Plasma Concentration (Tmax) of Revumenib(Cycle 1 Day 7, Cycle 1 Day 14, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 5 Day 1 (Cycle length=28 days))
- Phase 1b: Time to Maximum Plasma Concentration (Tmax) of Revumenib(Cycle 1 Day 7, Cycle 1 Day 14, Cycle 2 Day 8, Cycle 2 Day 15 (Cycle length=28 days))
- Phase 1b: Area Under the Plasma Concentration Versus Time Curve (AUC0-t) of Revumenib(Cycle 1 Day 7, Cycle 1 Day 14, Cycle 2 Day 8, Cycle 2 Day 15 (Cycle length=28 days))
- Phase 2: Area Under The Concentration Time Curve of Revumenib(Up to 2.2 years)
- Phase 2: Maximum Plasma Concentration (Cmax) of Revumenib(Up to 2.2 years)
- Phase 2: Time to Maximum Plasma Concentration (Tmax) of Revumenib(Up to 2.2 years)
- Phase 2: Number of Participants With TEAEs(Up to 2.2 years)
- Phase 2: Overall Survival (OS)(Up to 2.2 years)
- Phase 2: Disease Control Rate (DCR) at 6 Cycles (28-Day Cycles) as Assessed by Blinded Radiographic Review(Up to 2.2 years)
- Phase 2: ORR as Assessed by Blinded Radiographic Review(Up to 2.2 years)
- Phase 2: Duration of Response (DOR) as Assessed by Blinded Radiographic Review(Up to 2.2 years)
- Phase 2: Disease Control Rate (DCR) at 6 Cycles (28-Day Cycles) as Assessed by the Investigator(Up to 2.2 years)
- Phase 2: Overall Response Rate (ORR) as Assessed by the Investigator(Up to 2.2 years)
- Phase 2: DOR as Assessed by the Investigator(Up to 2.2 years)