RecruitingInterventionalPhase 1

A Multicenter, Open-label, First-in-Human Study of TYRA-200 in Advanced Intrahepatic Cholangiocarcinoma and Other Solid Tumors With Activating FGFR2 Gene Alterations (SURF-201)

NCT ID: NCT06160752Sponsor: Tyra Biosciences, IncLast updated: 2024-10-03

Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of TYRA-200 in cancers with FGFR2 activating gene alterations, including unresectable locally advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors.

Detailed description

This is a single arm, multi-part, phase 1 clinical trial studying TYRA-200, a novel, potent fibroblast growth factor receptor (FGFR) 1/2/3 tyrosine kinase inhibitor, in unresectable locally advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors with activating alterations in FGFR2. Part A is a dose escalation study in participants with any advanced solid tumor with FGFR/FGF pathway alterations who have exhausted approved standard therapies. Part A will evaluate the safety, tolerability, and PK of TYRA-200 to determine the optimal and maximum tolerated dose (MTD). Part B will evaluate the preliminary antitumor activity of TYRA-200 in participants with unresectable locally advanced/metastatic intrahepatic cholangiocarcinoma who have previously received an FGFR inhibitor and have FGFR2 kinase-domain mutations resistant to other FGFR inhibitors.

Arms & interventions

DrugPhase 1 Part A - dose escalation TYRA-200 taken once daily by mouth in 28-day cycles
TYRA-200 is an oral, novel potent FGFR 1/2/3 tyrosine kinase inhibitor that targets tumors that contain activating gene alterations of FGFR2.
DrugPhase 1 Part B - dose expansion TYRA-200 taken once daily by mouth in 28-day cycles
TYRA-200 is an oral, novel potent FGFR 1/2/3 tyrosine kinase inhibitor that targets tumors that contain activating gene alterations of FGFR2.

Outcome measures

Primary

Phase 1 Part A: To determine the maximum tolerated dose (MTD) of TYRA-200.
Time frame: Initiation of study treatment through 28 Days
Phase 1 Part B: To determine the optimal dose of TYRA-200.
Time frame: Initiation of study treatment through 28 days (up to approximately 18 months

Secondary

Number of participants with adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability.
Time frame: From day 1 treatment through 28-days post treatment (up to 2 years)
Frequency in changes in laboratory parameters and physical signs of toxicity.
Time frame: From day 1 treatment through 28-days post treatment (up to 2 years)
Pharmacokinetics: maximum plasma concentration (Cmax).
Time frame: From Day 1 through Cycle 3 Day 1 (each cycle is 28 days)
Pharmacokinetics: time to reach maximum plasma concentration (Tmax).
Time frame: From Day 1 through Cycle 3 Day 1 (each cycle is 28 days)
Pharmacokinetics: area under the plasma concentration-time curve (AUC).
Time frame: From Day 1 through Cycle 3 Day 1 (each cycle is 28 days)
Pharmacokinetics: half-life of Tyra-200 (t1/2).
Time frame: From Day 1 through Cycle 3 Day 1 (each cycle is 28 days)
Overall response rate (ORR) defined as the proportion of participants with complete response (CR) or partial response (PR) as determined by the investigator using RECIST V1.1.
Time frame: From enrollment, every 8 or 12 weeks (up to 2 years)
Duration of response defined as the time from the initial CR or PR to the time of relapse or death, whichever occurs first among participant with an objective response.
Time frame: From enrollment, every 8 or 12 weeks (up to 5 years)
Disease control rate defined as the proportion of participants having a CR, PR or stable disease (SD) for >12 weeks.
Time frame: From enrollment up to 5 years
Time to response defined as time to first CR or PR that is subsequently confirmed according to RECIST v1.1.
Time frame: Up to 5 years
Progression-free survival defined as the time from the date of first study drug administration to the earliest date of documented disease progression or death.
Time frame: From the date of the first dose of study drug until disease progression or death as assessed up to the last efficacy assessment for disease progression (up to 5 years)

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

Inclusion Criteria: Phase 1 Part A * Men and women 18 years of age or older. * Eastern Cooperative Oncology Group (ECOG) performance status of ≤1. * Any histologically confirmed advanced solid tumor with FGFR/FGF pathway alterations including FGFR gene mutations, fusions, and amplifications, as well as gene amplifications of FGFR ligands, who have exhausted or refused approved standard therapies. * Evaluable disease according to RECIST v1.1. Phase 1 Part B * Men and women 18 years of age or older. * Eastern Cooperative Oncology Group (ECOG) performance status of ≤1. * Histologically confirmed locally advanced/metastatic intrahepatic cholangiocarcinoma with a previously identified FGFR2 gene mutation or rearrangement. * Must have received a prior FGFR inhibitor. Participants may have received more than 1 prior FGFR inhibitor. * Presence of an FGFR2 kinase domain mutation that confers resistance to previous/other FGFR inhibitors; resistance mutations should be identified by a US Food and Drug Administration authorized/approved companion diagnostic or a Clinical Laboratory Improvement Amendments (CLIA) validated local test performed in a certified laboratory. * At least 1 measurable lesion by RECIST v1.1. Exclusion Criteria: * Discontinued a prior anti-FGFR therapy due to significant toxicity, defined as hepatotoxicity ≥Grade 3 or any Grade 4 toxicity according to CTCAE v5.0. * Has a serum phosphorus level \> upper limit of normal (ULN) during screening that remains \>ULN despite medical management. * Any ocular condition likely to increase the risk of eye toxicity. * History of or current uncontrolled cardiovascular disease. * Active, symptomatic, or untreated brain metastases. * Gastrointestinal disorders that will affect oral administration or absorption of TYRA-200. * Females who are pregnant, breastfeeding, or planning to become pregnant and males who plan to father a child while enrolled in this study.