Clinical Trials/NCT05731947

NCT05731947

Completed

Phase 1

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

Syndax Pharmaceuticals6 sites in 1 country42 target enrollmentApril 4, 2023

ConditionsColorectal Cancer Solid Tumors

InterventionsRevumenib Chemotherapy

DrugsRevumenib Chemotherapy

Overview

Phase: Phase 1
Intervention: Revumenib
Conditions: Colorectal Cancer
Sponsor: Syndax Pharmaceuticals
Enrollment: 42
Locations: 6
Primary Endpoint: Phase 1a: Number of Participants Experiencing Dose Limiting Toxicities
Status: Completed
Last Updated: 3 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

April 4, 2023

End Date

June 30, 2025

Last Updated

3 months ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Syndax Pharmaceuticals

Responsible Party

Sponsor

Eligibility Criteria

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

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

Arms & Interventions

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.

Intervention: Revumenib

Phase 1b: Signal-Seeking

Participants will receive revumenib tablets TID or BID from Day 1 of each 28-day cycle.

Intervention: Revumenib

Phase 2: Revumenib

Participants will receive revumenib tablets TID or BID from Day 1 of each 28-day cycle.

Intervention: Revumenib

Phase 2: Chemotherapy

Participants will receive chemotherapy from Day 1 of each 28-day cycle.

Intervention: Chemotherapy

Outcomes

Primary Outcomes

Phase 1a: Number of Participants Experiencing Dose Limiting Toxicities

Time Frame: Up to Day 29

Phase 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)

Time Frame: Approximately 12 months

Phase 1b: Disease Control Rate (DCR)

Time Frame: Approximately 6 months

Phase 1b: Overall Response Rate (ORR)

Time Frame: Approximately 6 months

Phase 2: Progression Free Survival (PFS)

Time Frame: Approximately 4 months

Secondary Outcomes

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)