Evaluation of Revumenib in Participants With Colorectal Cancer and Other Solid Tumors
Phase 1
Active, not recruiting
- Conditions
- Colorectal CancerSolid Tumors
- Interventions
- Drug: Chemotherapy
- Registration Number
- NCT05731947
- Lead Sponsor
- Syndax Pharmaceuticals
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 42
Inclusion Criteria
- 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
Key
Exclusion Criteria
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 2: Revumenib Revumenib Participants will receive revumenib tablets TID or BID from Day 1 of each 28-day cycle. Phase 2: Chemotherapy Chemotherapy Participants will receive chemotherapy from Day 1 of each 28-day cycle. Phase 1a: Dose Escalation Revumenib 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. Phase 1b: Signal-Seeking Revumenib Participants will receive revumenib tablets TID or BID from Day 1 of each 28-day cycle.
- Primary Outcome Measures
Name Time Method Phase 1b: Overall Response Rate (ORR) Approximately 6 months Phase 2: Progression Free Survival (PFS) Approximately 4 months Phase 1a: Number of Participants Experiencing Dose Limiting Toxicities Up to Day 29 Phase 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) Approximately 12 months Phase 1b: Disease Control Rate (DCR) Approximately 6 months
- Secondary Outcome Measures
Name Time Method Phase 2: AUC of Revumenib Predose up to approximately 6 months 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: Duration of Response (DOR) as Assessed by Blinded Radiographic Review Approximately 3 years 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: Cmax of Revumenib Predose up to approximately 6 months Phase 2: Tmax 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
Trial Locations
- Locations (6)
Honor Health Research Institute
🇺🇸Scottsdale, Arizona, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Memorial Sloan Kettering Cancer Center
🇺🇸Manhattan, New York, United States
Gabrail Cancer Center
🇺🇸Canton, Ohio, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Inova Schar Cancer Institute
🇺🇸Fairfax, Virginia, United States