Safety and Preliminary Anti-Tumor Activity of TYRA-300 in Advanced Urothelial Carcinoma and Other Solid Tumors With FGFR3 Gene Alterations (SURF301)

Tyra Biosciences

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: FGFR3 Gene Alteration; Solid Tumor; Non-muscle-invasive Bladder Cancer; Solid Tumor, Adult; Advanced Solid Tumor; Urothelial Carcinoma; FGFR3 Gene Mutation; Locally Advanced Urothelial Carcinoma; Metastatic Urothelial Carcinoma; Urinary Tract Carcinoma; Urinary Tract Cancer; Bladder Cancer; Urinary Tract Tumor; Advanced Urothelial Carcinoma

Treatments: Drug: TYRA-300

Study type: Interventional

Funder types: Industry

Identifiers

NCT05544552

TYR300-101

Details and patient eligibility

About

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of TYRA-300 in cancers with FGFR3 activating gene alterations, including locally advanced/metastatic urothelial carcinoma of the bladder and urinary tract and other advanced solid tumors.

Full description

This is a single arm, multi-part, phase 1/2 global trial studying TYRA-300, a novel, potent fibroblast growth factor receptor (FGFR) 3-selective tyrosine kinase inhibitor, in advanced/metastatic urothelial carcinoma of the bladder and urinary tract, that contain activating gene alterations of FGFR3. Phase 1 is a dose-escalation study to evaluate the safety, tolerability, and PK of TYRA-300 to determine the optimal and maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Phase 2 will evaluate the preliminary antitumor activity of TYRA-300 in cancers with FGFR3 activating gene alterations, including locally advanced/metastatic urothelial carcinoma of the bladder and urinary tract and other advanced solid tumors.

Enrollment: 310 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

Phase 1 Part A and Part B

• Men and women 18 years of age or older.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
• Histologically confirmed advanced solid tumor who have exhausted standard therapeutic options.
• Evaluable (Part A) or measurable (Part B) disease according to RECIST v1.1.
• Histologically confirmed advanced solid tumor with an eligible FGFR3 gene mutation or fusion (Part B).

Phase 2

• Men and women 18 years of age or older.

• ECOG performance status of 0-2 or Karnofsky Performance Scale (KPS) >70.

• At least 1 measurable lesion by RECIST v1.1.

• Histologically confirmed locally advanced/metastatic tumor in one of the following categories:

  • Urothelial carcinoma with an eligible FGFR3 gene mutation or rearrangement who have progressed on a prior FGFR inhibitor and presence of a resistance mutation or other kinase domain mutation.
  • Urothelial carcinoma with an eligible FGFR3 gene mutation or rearrangement who has not received a prior FGFR inhibitor.
  • Any solid tumor with an eligible FGFR3 gene mutation or rearrangement.

Exclusion Criteria (All Phases):

• 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-300.
• Females who are pregnant, breastfeeding, or planning to become pregnant and males who plan to father a child while enrolled in this study.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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310 participants in 3 patient groups

Phase 1 Part A - dose escalation

Experimental group

Description:

TYRA-300 taken once daily by mouth in 28-day cycles starting at 10 mg daily.

Treatment:

Drug: TYRA-300

Phase 1 Part B - dose expansion

Experimental group

Description:

TYRA-300 taken once or twice daily by mouth in 28-day cycles.

Treatment:

Drug: TYRA-300

Phase 2

Experimental group

Description:

TYRA-300 taken once or twice daily by mouth in 28-day cycles at doses determined during Phase 1.

Treatment:

Drug: TYRA-300