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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05731947
• Other study ID #: SNDX-5613-0706
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 4, 2023
• Est. completion date: August 2027

Study information

• Verified date: January 2024
• Source: Syndax Pharmaceuticals
• Contact: Syndax Pharmaceuticals
• Phone: 781-419-1400
• Email: clinicaltrials[@]syndax.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 158
• Est. completion date: August 2027
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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
• 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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Solid Tumors

Intervention

Drug:
• SNDX-5613
SNDX-5613 administered orally with or without food. Participants may continue to receive treatment until disease progression or until they experience unacceptable toxicity.
• Chemotherapy
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.

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Gabrail Cancer Center	Canton	Ohio
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	Memorial Sloan Kettering Cancer Center	Manhattan	New York
United States	Honor Health Research Institute	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Syndax Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1a: Number of Participants Experiencing Dose Limiting Toxicities		Up to Day 29
Primary	Phase 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)		Approximately 12 months
Primary	Phase 1b: Disease Control Rate (DCR) at 6 Cycles (28-Day Cycles)		Approximately 6 months
Primary	Phase 1b: Overall Response Rate (ORR)		Approximately 6 months
Primary	Phase 2: Progression Free Survival (PFS)		Approximately 4 months
Secondary	Phase 1: Maximum Plasma Concentration (Cmax) of SNDX-5613		Predose up to approximately 12 months
Secondary	Phase 1: Time to Maximum Plasma Concentration (Tmax) of SNDX-5613		Predose up to approximately 12 months
Secondary	Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of SNDX-5613		Predose up to approximately 12 months
Secondary	Phase 2: AUC of SNDX-5613		Predose up to approximately 6 months
Secondary	Phase 2: Cmax of SNDX-5613		Predose up to approximately 6 months
Secondary	Phase 2: Tmax of SNDX-5613		Predose up to approximately 6 months
Secondary	Phase 2: Number of Participants Experiencing TEAEs		Approximately 3 years
Secondary	Phase 2: Overall Survival (OS)		Approximately 5 years
Secondary	Phase 2: DCR at 6 Cycles (28-Day Cycles) as Assessed by Blinded Radiographic Review		Approximately 6 months
Secondary	Phase 2: ORR as Assessed by Blinded Radiographic Review Using Response Evaluation Criteria in Solid Tumors (RECIST), version (v)1.1		Approximately 6 months
Secondary	Phase 2: Duration of Response (DOR) as Assessed by Blinded Radiographic Review		Approximately 3 years
Secondary	Phase 2: DCR at 6 Cycles (28-Day Cycles) as Assessed by the Investigator		Approximately 6 months
Secondary	Phase 2: ORR as Assessed by the Investigator per RECIST v1.1		Approximately 6 months
Secondary	Phase 2: DOR as Assessed by the Investigator		Approximately 3 years