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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Colorectal Cancer, Solid Tumors

Intervention / Treatment
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* Drug: SNDX-5613
* Drug: Chemotherapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional 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)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1a: Dose Escalation<br>Participants will receive SNDX-5613 three times a day (TID) from Day 1 of each 28-day cycle. | Drug: SNDX-5613<br>* 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.<br>|
| Experimental: Phase 1b: Signal-Seeking<br>Participants will receive SNDX-5613 TID from Day 1 of each 28-day cycle. | Drug: SNDX-5613<br>* 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.<br>|
| Experimental: Phase 2: SNDX-5613<br>Participants will receive SNDX-5613 from Day 1 of each 28-day cycle. | Drug: SNDX-5613<br>* 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.<br>|
| Active Comparator: Phase 2: Chemotherapy<br>Participants will receive chemotherapy from Day 1 of each 28-day cycle. | Drug: Chemotherapy<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) at 6 Cycles (28-Day Cycles) |  | Approximately 6 months | 
| Phase 1b: Overall Response Rate (ORR) |  | Approximately 6 months | 
| Phase 2: Progression Free Survival (PFS) |  | Approximately 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Maximum Plasma Concentration (Cmax) of SNDX-5613 |  | Predose up to approximately 12 months | 
| Phase 1: Time to Maximum Plasma Concentration (Tmax) of SNDX-5613 |  | Predose up to approximately 12 months | 
| Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of SNDX-5613 |  | Predose up to approximately 12 months | 
| Phase 2: AUC of SNDX-5613 |  | Predose up to approximately 6 months | 
| Phase 2: Cmax of SNDX-5613 |  | Predose up to approximately 6 months | 
| Phase 2: Tmax of SNDX-5613 |  | Predose up to approximately 6 months | 
| Phase 2: Number of Participants Experiencing TEAEs |  | Approximately 3 years | 
| 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 2: DOR as Assessed by the Investigator |  | Approximately 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SNDX-5613, Revumenib, Menin