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Evaluation of SNDX-5613 in Participants With Colorectal Cancer and Other Solid Tumors

Primary Purpose

Colorectal Cancer, Solid Tumors

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
SNDX-5613
Chemotherapy
Sponsored by
Syndax Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring SNDX-5613, Revumenib, Menin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 enrollment 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 first study drug 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 SNDX-5613 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 Participant has another known additional malignancy that is progressing or requires active treatment (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). Prior history of other cancer is allowed, if there is no active disease within the prior 5 years

Sites / Locations

  • Honor Health Research Institute
  • Massachusetts General HospitalRecruiting
  • Gabrail Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Active Comparator

Arm Label

Phase 1a: Dose Escalation

Phase 1b: Signal-Seeking

Phase 2: SNDX-5613

Phase 2: Chemotherapy

Arm Description

Participants will receive SNDX-5613 three times a day (TID) from Day 1 of each 28-day cycle.

Participants will receive SNDX-5613 TID from Day 1 of each 28-day cycle.

Participants will receive SNDX-5613 from Day 1 of each 28-day cycle.

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

Outcomes

Primary Outcome Measures

Phase 1a: Number of Participants Experiencing Dose Limiting Toxicities
Phase 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Phase 1b: Disease Control Rate (DCR) at 6 Cycles (28-Day Cycles)
Phase 1b: Overall Response Rate (ORR)
Phase 2: Progression Free Survival (PFS)

Secondary Outcome Measures

Phase 1: Maximum Plasma Concentration (Cmax) of SNDX-5613
Phase 1: Time to Maximum Plasma Concentration (Tmax) of SNDX-5613
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of SNDX-5613
Phase 2: AUC of SNDX-5613
Phase 2: Cmax of SNDX-5613
Phase 2: Tmax of SNDX-5613
Phase 2: Number of Participants Experiencing TEAEs
Phase 2: Overall Survival (OS)
Phase 2: DCR at 6 Cycles (28-Day Cycles) as Assessed by Blinded Radiographic Review
Phase 2: ORR as Assessed by Blinded Radiographic Review Using Response Evaluation Criteria in Solid Tumors (RECIST), version (v)1.1
Phase 2: Duration of Response (DOR) as Assessed by Blinded Radiographic Review
Phase 2: DCR at 6 Cycles (28-Day Cycles) as Assessed by the Investigator
Phase 2: ORR as Assessed by the Investigator per RECIST v1.1
Phase 2: DOR as Assessed by the Investigator

Full Information

First Posted
February 7, 2023
Last Updated
July 14, 2023
Sponsor
Syndax Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT05731947
Brief Title
Evaluation of SNDX-5613 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

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 4, 2023 (Actual)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
September 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Syndax Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study will evaluate the safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of SNDX-5613 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 SNDX-5613.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Solid Tumors
Keywords
SNDX-5613, Revumenib, Menin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
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
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
158 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase 1a: Dose Escalation
Arm Type
Experimental
Arm Description
Participants will receive SNDX-5613 three times a day (TID) from Day 1 of each 28-day cycle.
Arm Title
Phase 1b: Signal-Seeking
Arm Type
Experimental
Arm Description
Participants will receive SNDX-5613 TID from Day 1 of each 28-day cycle.
Arm Title
Phase 2: SNDX-5613
Arm Type
Experimental
Arm Description
Participants will receive SNDX-5613 from Day 1 of each 28-day cycle.
Arm Title
Phase 2: Chemotherapy
Arm Type
Active Comparator
Arm Description
Participants will receive chemotherapy from Day 1 of each 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
SNDX-5613
Intervention Description
Administered either as oral tablets or oral capsule with or without food. Participants may continue to receive treatment until disease progression or until they experience unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Chemotherapy
Intervention Description
Either Lonsurf® or Stivarga® administered per the investigator's choice at the respective drug label's dose and schedule. Participants may continue to receive treatment until disease progression or until they experience unacceptable toxicity.
Primary Outcome Measure Information:
Title
Phase 1a: Number of Participants Experiencing Dose Limiting Toxicities
Time Frame
Up to Day 29
Title
Phase 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Time Frame
Approximately 12 months
Title
Phase 1b: Disease Control Rate (DCR) at 6 Cycles (28-Day Cycles)
Time Frame
Approximately 6 months
Title
Phase 1b: Overall Response Rate (ORR)
Time Frame
Approximately 6 months
Title
Phase 2: Progression Free Survival (PFS)
Time Frame
Approximately 4 months
Secondary Outcome Measure Information:
Title
Phase 1: Maximum Plasma Concentration (Cmax) of SNDX-5613
Time Frame
Predose up to approximately 12 months
Title
Phase 1: Time to Maximum Plasma Concentration (Tmax) of SNDX-5613
Time Frame
Predose up to approximately 12 months
Title
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of SNDX-5613
Time Frame
Predose up to approximately 12 months
Title
Phase 2: AUC of SNDX-5613
Time Frame
Predose up to approximately 6 months
Title
Phase 2: Cmax of SNDX-5613
Time Frame
Predose up to approximately 6 months
Title
Phase 2: Tmax of SNDX-5613
Time Frame
Predose up to approximately 6 months
Title
Phase 2: Number of Participants Experiencing TEAEs
Time Frame
Approximately 3 years
Title
Phase 2: Overall Survival (OS)
Time Frame
Approximately 5 years
Title
Phase 2: DCR at 6 Cycles (28-Day Cycles) as Assessed by Blinded Radiographic Review
Time Frame
Approximately 6 months
Title
Phase 2: ORR as Assessed by Blinded Radiographic Review Using Response Evaluation Criteria in Solid Tumors (RECIST), version (v)1.1
Time Frame
Approximately 6 months
Title
Phase 2: Duration of Response (DOR) as Assessed by Blinded Radiographic Review
Time Frame
Approximately 3 years
Title
Phase 2: DCR at 6 Cycles (28-Day Cycles) as Assessed by the Investigator
Time Frame
Approximately 6 months
Title
Phase 2: ORR as Assessed by the Investigator per RECIST v1.1
Time Frame
Approximately 6 months
Title
Phase 2: DOR as Assessed by the Investigator
Time Frame
Approximately 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 enrollment 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 first study drug 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 SNDX-5613 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 Participant has another known additional malignancy that is progressing or requires active treatment (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). Prior history of other cancer is allowed, if there is no active disease within the prior 5 years
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Syndax Pharmaceuticals
Phone
781-419-1400
Email
clinicaltrials@syndax.com
Facility Information:
Facility Name
Honor Health Research Institute
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Name
Gabrail Cancer Center
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Individual Site Status
Not yet recruiting

12. IPD Sharing Statement

Learn more about this trial

Evaluation of SNDX-5613 in Participants With Colorectal Cancer and Other Solid Tumors

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