A Study to Assess the Safety, Pharmacokinetics, and Antitumor Activity of Oral TACH101 in Participants With Advanced or Metastatic Cancer

• ClinicalTrials.gov Identifier: NCT05076552
• Recruitment Status: Recruiting
• First Posted: October 13, 2021
• Last Update Posted: April 8, 2024
• Sponsor: Tachyon Therapeutics, Inc.
• Information provided by (Responsible Party): Tachyon Therapeutics, Inc.

Tracking Information

• First Submitted Date: September 30, 2021
• First Posted Date: October 13, 2021
• Last Update Posted Date: April 8, 2024
• Actual Study Start Date: February 17, 2023
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 4, 2024)

• Phase 1a Dose Escalation: MTD of TACH101 [ Time Frame: Day 1 to End of Treatment (up to approximately 201 days) ]
• Phase 1a Dose Escalation: RP2D of TACH101 [ Time Frame: Day 1 to End of Treatment (up to approximately 201 days) ]
• Phase 1b Dose Expansion: ORR [ Time Frame: Day 1 to End of Treatment (up to approximately 201 days) ]

Original Primary Outcome Measures (submitted: September 30, 2021)

• Phase 1 Dose Escalation: Maximum Tolerated Dose (MTD) of TACH101 [ Time Frame: Day 1 to End of Treatment (up to approximately 201 days) ]
• Phase 1 Dose Escalation: Recommended Phase 2 Dose (RP2D) of TACH101 [ Time Frame: Day 1 to End of Treatment (up to approximately 201 days) ]
• Phase 1b Dose Expansion: Objective Response Rate (ORR) [ Time Frame: Day 1 to End of Treatment (up to approximately 201 days) ]

Current Secondary Outcome Measures (submitted: April 4, 2024)

• Phase 1a Dose Escalation: Number of Participants Who Experience Dose-limiting Toxicities (DLTs) [ Time Frame: Cycle 1 Day 1 up to Cycle 1 Day 28 (cycle length = 28 days) ]
• Phase 1a Dose Escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Lead-in Day 1 to End of Treatment (up to approximately 204 days) ]
  A TEAE is defined as any untoward medical occurrence in participants that happened after study drug administration. Any clinically significant abnormalities in vital signs, clinical laboratory tests, or electrocardiograms (ECGs) will be recorded as adverse events (AEs).
• Phase 1a Dose Escalation: Area Under the Plasma Concentration-Time Curve (AUC) for TACH101 [ Time Frame: Lead-in Day 1 to Cycle 8 Day 1 (cycle = 28 days) ]
• Phase 1a Dose Escalation: Maximum Concentration (Cmax) of TACH101 [ Time Frame: Lead-in Day 1 to Cycle 8 Day 1 (cycle = 28 days) ]
• Phase 1a Dose Escalation: Observed Predose Plasma Concentration During Multiple Dosing (Ctrough) of TACH101 [ Time Frame: Lead-in Day 1 to Cycle 8 Day 1 (cycle = 28 days) ]
• Phase 1a Dose Escalation: Time to Reach Maximum Concentration (tmax) for TACH101 [ Time Frame: Lead-in Day 1 to Cycle 8 Day 1 (cycle = 28 days) ]
• Phase 1a Dose Escalation: Apparent Terminal Elimination Half-life (t1/2) of TACH101 [ Time Frame: Lead-in Day 1 to Cycle 8 Day 1 (cycle = 28 days) ]
• Phase 1a Dose Escalation: Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) of TACH101 [ Time Frame: Lead-in Day 1 to Cycle 8 Day 1 (cycle = 28 days) ]
• Phase 1a Dose Escalation: Apparent Clearance After Extravascular Administration (CL/F) of TACH101 [ Time Frame: Lead-in Day 1 to Cycle 8 Day 1 (cycle = 28 days) ]
• Phase 1a Dose Escalation: ORR [ Time Frame: Day 1 to End of Treatment (up to approximately 201 days) ]
• Phase 1a Dose Escalation: Duration of Response (DOR) [ Time Frame: Day 1 to End of Treatment (up to approximately 201 days) ]
• Phase 1a Dose Escalation: Clinical Benefit Rate (CBR) [ Time Frame: Day 1 to End of Treatment (up to approximately 201 days) ]
• Phase 1b Dose Expansion: Number of Participants With TEAEs [ Time Frame: Lead-in Day 1 to End of Treatment (up to approximately 203 days) ]
  A TEAE is defined as any untoward medical occurrence in participants that happened after study drug administration. Any clinically significant abnormalities in vital signs, clinical laboratory tests, or ECGs will be recorded as AEs.
• Phase 1b Dose Expansion: Concentration at 2 Hours Postdose (C2h) of TACH101 [ Time Frame: Cycle 1 Day 1 to Cycle 10 Day 1 (cycle = 28 days) ]
• Phase 1b Dose Expansion: Cmax of TACH101 [ Time Frame: Cycle 1 Day 1 to Cycle 10 Day 1 (cycle = 28 days) ]
• Phase 1b Dose Expansion: Ctrough of TACH101 [ Time Frame: Cycle 1 Day 1 to Cycle 10 Day 1 (cycle = 28 days) ]
• Phase 1b Dose Expansion: DOR [ Time Frame: Day 1 to End of Treatment (up to approximately 201 days) ]
• Phase 1b Dose Expansion: CBR [ Time Frame: Day 1 to End of Treatment (up to approximately 201 days) ]

Original Secondary Outcome Measures (submitted: September 30, 2021)

• Phase 1 Dose Escalation: Number of Participants Who Experience Dose-limiting Toxicities (DLTs) [ Time Frame: Cycle 1 Day 1 up to Cycle 1 Day 28 (cycle length = 28 days) ]
• Phase 1 Dose Escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Lead-in Day 1 to End of Treatment (up to approximately 203 days) ]
  A TEAE is defined as any untoward medical occurrence in participants that happened after study drug administration. Any clinically significant abnormalities in vital signs, clinical laboratory tests, or electrocardiograms (ECGs) will be recorded as AEs.
• Phase 1 Dose Escalation: Area Under the Plasma Concentration-Time Curve (AUC) for TACH101 [ Time Frame: Lead-in Day 1 to Cycle 4 Day 1 (cycle = 28 days) ]
• Phase 1 Dose Escalation: Maximum Concentration (Cmax) of TACH101 [ Time Frame: Lead-in Day 1 to Cycle 4 Day 1 (cycle = 28 days) ]
• Phase 1 Dose Escalation: Observed Predose Plasma Concentration During Multiple Dosing (Ctrough) of TACH101 [ Time Frame: Lead-in Day 1 to Cycle 4 Day 1 (cycle = 28 days) ]
• Phase 1 Dose Escalation: Time to Reach Maximum Concentration (tmax) for TACH101 [ Time Frame: Lead-in Day 1 to Cycle 4 Day 1 (cycle = 28 days) ]
• Phase 1 Dose Escalation: Apparent Terminal Elimination Half-life (t1/2) of TACH101 [ Time Frame: Lead-in Day 1 to Cycle 4 Day 1 (cycle = 28 days) ]
• Phase 1 Dose Escalation: Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) of TACH101 [ Time Frame: Lead-in Day 1 to Cycle 4 Day 1 (cycle = 28 days) ]
• Phase 1 Dose Escalation: Apparent Clearance After Extravascular Administration (CL/F) of TACH101 [ Time Frame: Lead-in Day 1 to Cycle 4 Day 1 (cycle = 28 days) ]
• Phase 1 Dose Escalation: Objective Response Rate (ORR) [ Time Frame: Day 1 to End of Treatment (up to approximately 201 days) ]
• Phase 1 Dose Escalation: Duration of Response (DOR) [ Time Frame: Day 1 to End of Treatment (up to approximately 201 days) ]
• Phase 1 Dose Escalation: Clinical Benefit Rate (CBR) [ Time Frame: Day 1 to End of Treatment (up to approximately 201 days) ]
• Phase 1b Dose Expansion: Number of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Lead-in Day 1 to End of Treatment (up to approximately 203 days) ]
  A TEAE is defined as any untoward medical occurrence in participants that happened after study drug administration. Any clinically significant abnormalities in vital signs, clinical laboratory tests, or electrocardiograms (ECGs) will be recorded as AEs.
• Phase 1b Dose Expansion: Concentration at 2 Hours Postdose (C2h) of TACH101 [ Time Frame: Cycle 1 Day 1 to Cycle 6 Day 1 (cycle = 28 days) ]
• Phase 1b Dose Expansion: Maximum Concentration (Cmax) of TACH101 [ Time Frame: Cycle 1 Day 1 to Cycle 6 Day 1 (cycle = 28 days) ]
• Phase 1b Dose Expansion: Observed Predose Plasma Concentration During Multiple Dosing (Ctrough) of TACH101 [ Time Frame: Cycle 1 Day 1 to Cycle 6 Day 1 (cycle = 28 days) ]
• Phase 1b Dose Expansion: Duration of Response (DOR) [ Time Frame: Day 1 to End of Treatment (up to approximately 201 days) ]
• Phase 1b Dose Expansion: Clinical Benefit Rate (CBR) [ Time Frame: Day 1 to End of Treatment (up to approximately 201 days) ]
• Phase 1b Dose Expansion: Plasma Concentration of TACH101 [ Time Frame: Cycle 1 Day 1 to Cycle 6 Day 1 (cycle = 28 days) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Assess the Safety, Pharmacokinetics, and Antitumor Activity of Oral TACH101 in Participants With Advanced or Metastatic Cancer
• Official Title: A Phase 1a/1b Open-label Study to Assess the Safety, Pharmacokinetics, and Antitumor Activity of Oral TACH101 in Patients With Advanced or Metastatic Solid Tumors
• Brief Summary: The main objective for part 1a of the study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) and to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of oral TACH101 in participants with advanced and metastatic solid tumors. For part 1b, the main objective is the objective response rate (ORR) as assessed by radiographic progression measured by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Advanced Cancer
• Metastatic Solid Tumor
• Solid Tumor

Intervention

Drug: TACH101

Orally via capsules

Study Arms

• Experimental: Phase 1a: Dose Escalation
  In Phase 1a, participants will receive TACH101 in a 48 hour lead in period followed by repeated dosing at different dosing regimens in each 28 day cycle.
  Intervention: Drug: TACH101
• Experimental: Phase 1b: Dose Expansion

  In Phase 1b, participants will receive TACH101 at the RP2D identified in Phase 1a. Two cohorts of participants will be enrolled:

  • Participants with gastrointestinal cancers.
  • Participants with high microsatellite instability (MSI-H) metastatic colorectal cancer (CRC).
  Intervention: Drug: TACH101

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 30, 2021): 70
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2025
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written informed consent and privacy language as per national regulations must be obtained from the participant or legally authorized representative prior to any study-related procedures being performed.
• 18 years of age or older.
• Phase 1a: Participant must have advanced or metastatic solid tumor that has progressed or was non-responsive or intolerant to available therapies and for which no standard or available curative therapy exists, or, in the opinion of the investigator, is not a candidate for, or would be unlikely to tolerate or derive significant clinical benefit from, appropriate standard of care therapy.
• Phase 1b: Participants must have advanced or metastatic gastrointestinal tumors, or high microsatellite instability colorectal cancer (MSI-H CRC) that has progressed or was non-responsive or intolerant to standard therapy (e.g., fluoropyrimidine and oxaliplatin with or without bevacizumab), or, in the opinion of the investigator, is not a candidate for, or would be unlikely to tolerate or derive significant clinical benefit from, appropriate standard of care therapy. Participants with potentially curative therapy will not be enrolled (e.g., participants with CRC and oligometastatic disease who are candidates for resection). Participants with MSI-H CRC must have received a prior line of therapy with a checkpoint inhibitor. Note: For both Phase 1a and 1b, if a participant has available therapies but is determined to be ineligible by the investigator due to being unlikely to tolerate or benefit from available therapies, the reason for this must be documented in the medical record and case report form.
• Presence of advanced or metastatic disease that is measurable according to RECIST v 1.1.
• The participant must have recovered from toxicities related to any prior treatments (Grade ≤1) except alopecia, anorexia, or toxicity that is stable and poses no significant risk to the participant. Grade 2 peripheral neuropathy after documented treatment with taxanes and/or platinum-based therapy is allowed.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.

• Meets the following laboratory requirements at screening:

  1. Absolute neutrophil count (ANC) ≥1500/µL, platelet count ≥100,000/µL; and hemoglobin ≥9.0 g/dL.
  2. Total bilirubin ≤1.5× upper limit of normal (ULN) (Gilbert's syndrome ≤2.5×ULN).
  3. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤2.5×ULN.
  4. Creatinine clearance (CrCl) >60 mL/min by the Cockcroft-Gault formula: CrCl={([l 40-age (years)]×weight [kg])/(72× serum creatinine [mg/dL])}(×0.85 for females).
• Women of childbearing potential (WOCBP) must have a negative pregnancy test during the screening period before beginning treatment.
• WOCBP or men whose partner is a WOCBP agrees to use contraception while participating in this study, and for a minimum of 3 months for men and 6 months for women following the last dose of study treatment.

Exclusion Criteria:

Participants will be excluded from participation in the study if any of the following apply:

• Participants who have received allogenic hematologic stem cell transplant.
• Major surgery within 2 months prior to screening.
• Prior history of or concurrent secondary primary malignancy whose natural history or treatment has the potential to interfere with the safety and/or efficacy assessment of TACH101.
• Prior gastrectomy or upper bowel removal or any other gastrointestinal disorder that would interfere with the absorption or excretion of TACH101.
• Known or suspected brain metastases.

• Significant cardiovascular disease including any of the following:

  1. Myocardial infarction within 6 months prior to study entry.
  2. Uncontrolled angina within 1 month prior to study entry.
  3. Congestive heart failure New York Heart Association (NYHA) class III or IV, or a history of congestive heart failure NYHA class III or IV unless a screening echocardiogram or multigated acquisition (MUGA) scan performed within 3 months prior to study entry results in a left ventricular ejection fraction (LVEF) ≥45%.
  4. QT interval corrected by the Fridericia correction formula (QTcF) at screening >470 msec for both men and women.
  5. History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes).
  6. History of Mobitz II second degree or third degree heart block.
  7. Uncontrolled hypertension as indicated by a resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg at screening.
• Acute or chronic liver or kidney disease.
• Concurrent disease or any clinically significant abnormality following the investigator's review of the screening physical examination findings, 12-lead electrocardiogram (ECG) results, and clinical laboratory tests, which in the judgment of the investigator would interfere with the participant's participation in this study or evaluation of study results.
• Known or suspected hypersensitivity to any components of the formulation used for TACH101.
• Any ongoing anticancer therapy including; small molecules, immunotherapy, chemotherapy, monoclonal antibodies, or any other experimental drug. Prior therapy must be stopped at least 4 weeks or 5 half-lives (whichever is shorter) before first dose.
• Clinically significant active viral, bacterial or fungal infection requiring: Intravenous treatment with antimicrobial therapy completed less than 2 weeks prior to first dose, or oral treatment with antimicrobial therapy completed less than one week prior to first dose.
• Known history of infection with human immunodeficiency virus (HIV) hepatitis B, or hepatitis C.
• For Phase 1b, prior participation in Phase 1a.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Tachyon Therapeutics; 832-952-0829; TACH101study@tachyontx.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05076552
• Other Study ID Numbers: TACH101-CS-0001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Tachyon Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Tachyon Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Tachyon Therapeutics, Inc.
• Verification Date: April 2024