A Multicenter, Open-label Phase 1/2 Study of TYRA-300 in Advanced Urothelial Carcinoma and Other Solid Tumors with Activating FGFR3 Gene Alterations (SURF-301)

ENROLLING
Protocol # :
22-641
Conditions
Locally Advanced Urothelial Carcinoma
Metastatic Urothelial Carcinoma
Solid Tumor
Urothelial Carcinoma
Solid Tumor, Adult
Bladder Cancer
Non-muscle-invasive Bladder Cancer
FGFR3 Gene Mutation
FGFR3 Gene Alteration
Advanced Solid Tumor
Advanced Urothelial Carcinoma
Urinary Tract Cancer
Urinary Tract Tumor
Urinary Tract Carcinoma
Phase
I/II
Disease Sites
Neuroendocrine/Carcinoid
Gastroesophageal Junction
Gallbladder/Biliary
Other specified personal risk factors, not elsewhere classified
Lip, Oral Cavity and Pharynx
Esophagus
Stomach
Small Intestine
Colon
Rectum
Anus
Liver
Pancreas
Other Digestive Organ
Larynx
Lung
Other Respiratory and Intrathoracic Organs
Bones and Joints
Soft Tissue
Other Skin
Breast
Cervix
Corpus Uteri
Ovary
Other Female Genital
Prostate
Other Male Genital
Urinary Bladder
Kidney
Other Urinary
Eye and Orbit
Brain and Nervous System
Thyroid
Unknown Sites
Ill-Defined Sites
Other Endocrine System
Kaposi's Sarcoma
Melanoma, Skin
Principal Investigator
Mantia, Charlene
Site Research Nurses
Capulong, Florylene
Combs, Sarah
Grimes, Hayley
Hart, Kayla
Mackoul, Anna
Maurer, Kimberly
O’Neill, Kailene
Speth, Celia
Treveloni, Emily

Trial Description

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.

Eligibility Requirements

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 12 years of age or older.

- ECOG performance status of 0-2 or Karnofsky Performance Scale (KPS) >70 for
participants aged 12 to 17 years.

- 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.

22-641