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

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ClinicalTrials.gov Identifier: NCT05076552
Recruitment Status : Not yet recruiting
First Posted : October 13, 2021
Last Update Posted : October 13, 2021
Sponsor:
Information provided by (Responsible Party):
Tachyon Therapeutics, Inc.

Brief Summary:
The overall objective of this open-label, nonrandomized, 2-part Phase 1/1b 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 a 3 day on/4-day off weekly regimen (3/4 schedule) in participants with advanced and metastatic solid tumors. Each participant in the dose escalation phase will receive a single dose of TACH101 and be followed for 48 hours in the single-dose lead-in period.

Condition or disease Intervention/treatment Phase
Advanced Cancer Metastatic Solid Tumor Solid Tumor Drug: TACH101 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/1b Open-label Study to Assess the Safety, Pharmacokinetics, and Antitumor Activity of Oral TACH101 in Patients With Advanced or Metastatic Cancer
Estimated Study Start Date : January 6, 2022
Estimated Primary Completion Date : November 20, 2023
Estimated Study Completion Date : March 13, 2024

Arm Intervention/treatment
Experimental: Phase 1: Dose Escalation
In Phase 1, participants will receive TACH101 in a 48 hour single-dose lead-in period followed by repeated dosing on a 3-day on/4-day off schedule in each 28 day cycle.
Drug: TACH101
Orally via capsules

Experimental: Phase 1b: Dose Expansion

In Phase 1b, participants will receive TACH101 at the RP2D identified in Phase 1 on a 3-day on/4-day off schedule. Two cohorts of participants will be enrolled:

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




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

Secondary Outcome Measures :
  1. 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) ]
  2. 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.

  3. 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) ]
  4. Phase 1 Dose Escalation: Maximum Concentration (Cmax) of TACH101 [ Time Frame: Lead-in Day 1 to Cycle 4 Day 1 (cycle = 28 days) ]
  5. 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) ]
  6. 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) ]
  7. 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) ]
  8. 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) ]
  9. 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) ]
  10. Phase 1 Dose Escalation: Objective Response Rate (ORR) [ Time Frame: Day 1 to End of Treatment (up to approximately 201 days) ]
  11. Phase 1 Dose Escalation: Duration of Response (DOR) [ Time Frame: Day 1 to End of Treatment (up to approximately 201 days) ]
  12. Phase 1 Dose Escalation: Clinical Benefit Rate (CBR) [ Time Frame: Day 1 to End of Treatment (up to approximately 201 days) ]
  13. 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.

  14. 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) ]
  15. Phase 1b Dose Expansion: Maximum Concentration (Cmax) of TACH101 [ Time Frame: Cycle 1 Day 1 to Cycle 6 Day 1 (cycle = 28 days) ]
  16. 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) ]
  17. Phase 1b Dose Expansion: Duration of Response (DOR) [ Time Frame: Day 1 to End of Treatment (up to approximately 201 days) ]
  18. Phase 1b Dose Expansion: Clinical Benefit Rate (CBR) [ Time Frame: Day 1 to End of Treatment (up to approximately 201 days) ]
  19. Phase 1b Dose Expansion: Plasma Concentration of TACH101 [ Time Frame: Cycle 1 Day 1 to Cycle 6 Day 1 (cycle = 28 days) ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 1: 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 (eg, 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.

  • Presence of advanced or metastatic disease that is measurable or evaluable according to Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1. Participants in Phase 1b must have measurable disease as defined by RECIST.
  • 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)
    3. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤2.5×ULN
    4. Creatinine clearance (CrCl) >30 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 period of at least 30 days following termination 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.
  • Brain metastases: participants may participate provided the metastases are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of TACH101 and any neurologic symptoms are controlled and stable), they have no evidence of new or enlarged brain metastases, and they are clinically stable and off steroids for at least 7 days prior to TACH101.
  • 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 >450 msec for men or >470 msec for women.
    5. History of clinically significant ventricular arrhythmias (eg, 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 1.
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Responsible Party: Tachyon Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05076552    
Other Study ID Numbers: TACH101-CS-0001
First Posted: October 13, 2021    Key Record Dates
Last Update Posted: October 13, 2021
Last Verified: September 2021

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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
Keywords provided by Tachyon Therapeutics, Inc.:
Cancer
Solid Tumors
Advanced Cancer
TACH101
Metastatic Solid Tumor
Additional relevant MeSH terms:
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Neoplasms
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes