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

Tachyon Therapeutics, Inc.4 sites in 1 country30 target enrollmentFebruary 17, 2023

ConditionsAdvanced Cancer Metastatic Solid Tumor Solid Tumor

InterventionsTACH101

DrugsTACH101

Overview

Phase: Phase 1
Intervention: TACH101
Conditions: Advanced Cancer
Sponsor: Tachyon Therapeutics, Inc.
Enrollment: 30
Locations: 4
Primary Endpoint: Phase 1a Dose Escalation: MTD of TACH101
Status: Active, not recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

February 17, 2023

End Date

July 2025

Last Updated

last year

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Tachyon Therapeutics, Inc.

Responsible Party

Sponsor

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.
•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
•Meets the following laboratory requirements at screening:
•Absolute neutrophil count (ANC) ≥1500/µL, platelet count ≥100,000/µL; and hemoglobin ≥9.0 g/dL.
•Total bilirubin ≤1.5× upper limit of normal (ULN) (Gilbert's syndrome ≤2.5×ULN).

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 TACH
•Prior gastrectomy or upper bowel removal or any other gastrointestinal disorder that would interfere with the absorption or excretion of TACH
•Known or suspected brain metastases.
•Significant cardiovascular disease including any of the following:
•Myocardial infarction within 6 months prior to study entry.
•Uncontrolled angina within 1 month prior to study entry.
•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%.

Arms & Interventions

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: TACH101

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: TACH101

Outcomes

Primary Outcomes

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)

Secondary Outcomes

Phase 1a Dose Escalation: Area Under the Plasma Concentration-Time Curve (AUC) for TACH101(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(Lead-in Day 1 to Cycle 8 Day 1 (cycle = 28 days))
Phase 1a Dose Escalation: ORR(Day 1 to End of Treatment (up to approximately 201 days))
Phase 1a Dose Escalation: Duration of Response (DOR)(Day 1 to End of Treatment (up to approximately 201 days))
Phase 1a Dose Escalation: Clinical Benefit Rate (CBR)(Day 1 to End of Treatment (up to approximately 201 days))
Phase 1b Dose Expansion: Number of Participants With TEAEs(Lead-in Day 1 to End of Treatment (up to approximately 203 days))
Phase 1b Dose Expansion: Concentration at 2 Hours Postdose (C2h) of TACH101(Cycle 1 Day 1 to Cycle 10 Day 1 (cycle = 28 days))
Phase 1b Dose Expansion: Cmax of TACH101(Cycle 1 Day 1 to Cycle 10 Day 1 (cycle = 28 days))
Phase 1a Dose Escalation: Number of Participants Who Experience Dose-limiting Toxicities (DLTs)(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)(Lead-in Day 1 to End of Treatment (up to approximately 204 days))
Phase 1a Dose Escalation: Maximum Concentration (Cmax) of TACH101(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(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(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(Lead-in Day 1 to Cycle 8 Day 1 (cycle = 28 days))
Phase 1b Dose Expansion: CBR(Day 1 to End of Treatment (up to approximately 201 days))
Phase 1a Dose Escalation: Time to Reach Maximum Concentration (tmax) for TACH101(Lead-in Day 1 to Cycle 8 Day 1 (cycle = 28 days))
Phase 1b Dose Expansion: Ctrough of TACH101(Cycle 1 Day 1 to Cycle 10 Day 1 (cycle = 28 days))
Phase 1b Dose Expansion: DOR(Day 1 to End of Treatment (up to approximately 201 days))