Clinical trial NCT05731947: Evaluation of Revumenib in Participants With Colorectal Cancer and Other Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Colorectal Cancer
Solid Tumors
Keywords: SNDX-5613
Revumenib
Menin
Lead sponsor: Syndax Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2023-02-16
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Phase 1a dose escalation portion of the study will employ a Rolling 6 trial design, followed by a Phase 1b signal-seeking portion, and a Phase 2 randomized (2:1) signal confirmation portion.

Phase 1: Non-randomized; Phase 2: Randomized
Primary purpose: TREATMENT

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.

Eligibility criteria: Key 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

Primary outcomes:
measure: Phase 1a: Number of Participants Experiencing Dose Limiting Toxicities
timeFrame: Up to Day 29
measure: Phase 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
timeFrame: Approximately 12 months
measure: Phase 1b: Disease Control Rate (DCR)
timeFrame: Approximately 6 months
measure: Phase 1b: Overall Response Rate (ORR)
timeFrame: Approximately 6 months
measure: Phase 2: Progression Free Survival (PFS)
timeFrame: Approximately 4 months
Secondary outcomes:
measure: Phase 1: Maximum Plasma Concentration (Cmax) of Revumenib
timeFrame: Predose up to approximately 12 months
measure: Phase 1: Time to Maximum Plasma Concentration (Tmax) of Revumenib
timeFrame: Predose up to approximately 12 months
measure: Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Revumenib
timeFrame: Predose up to approximately 12 months
measure: Phase 2: AUC of Revumenib
timeFrame: Predose up to approximately 6 months
measure: Phase 2: Cmax of Revumenib
timeFrame: Predose up to approximately 6 months
measure: Phase 2: Tmax of Revumenib
timeFrame: Predose up to approximately 6 months
measure: Phase 2: Number of Participants Experiencing TEAEs
timeFrame: Approximately 3 years
measure: Phase 2: Overall Survival (OS)
timeFrame: Approximately 5 years
measure: Phase 2: DCR at 6 Cycles (28-Day Cycles) as Assessed by Blinded Radiographic Review
timeFrame: Approximately 6 months
measure: Phase 2: ORR as Assessed by Blinded Radiographic Review Using Response Evaluation Criteria in Solid Tumors (RECIST), version (v)1.1
timeFrame: Approximately 6 months
measure: Phase 2: Duration of Response (DOR) as Assessed by Blinded Radiographic Review
timeFrame: Approximately 3 years
measure: Phase 2: DCR at 6 Cycles (28-Day Cycles) as Assessed by the Investigator
timeFrame: Approximately 6 months
measure: Phase 2: ORR as Assessed by the Investigator per RECIST v1.1
timeFrame: Approximately 6 months
measure: Phase 2: DOR as Assessed by the Investigator
timeFrame: Approximately 3 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Honor Health Research Institute
state: Arizona
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Manhattan
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
Study officials:
References: