Ended Phase I and Phase II (Integrated)- First administration to humans Advanced Urothelial Carcinoma and Other Solid Tumors with Activating FGFR3 Gene Alterations

A Multicenter, Open-label Phase 1/2 Study of TYRA 300 in Advanced Urothelial Carcinoma and Other Solid Tumors

EU CTIS ID: 2023-507589-22-00

What this study is testing

To determine the optimal and MTDs, and RP2D of TYRA-300 in participants with advanced solid tumors (Phase 1, Parts A and B) To evaluate the preliminary antitumor activity of TYRA-300 at the RP2D in participants in selected tumor expansion cohorts with activating FGFR3 gene alterations (Phase 2)

  • Phase I and Phase II (Integrated)- First administration to humans

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

  • PHASE 1 PART A (1-10): Male and female participants who are 18 years of age or older on the day of signing the ICF.
  • Coronavirus disease 2019 (COVID-19) testing per local standards and regulations, and fulfills COVID-19 vaccination requirements as per local site regulations (if any). Participants with a positive test result for COVID-19 infection at Screening who fulfil all other study eligibility criteria can be rescreened following test normalization and clinical recovery.
  • PHASE 1 PART B (11-20): Male and female participants who are 18 years of age or older on the day of signing the ICF.
  • Life expectancy >12 weeks.
  • Ability to understand and sign the ICF and comply with study procedures.
  • ECOG PS ≤1.

You likely can't join if

  • Participant received chemotherapy, targeted therapy, immunotherapy, or an investigational therapy within 4 weeks or 5 half-lives, whichever is shorter, before the first dose of study drug (within 6 weeks for nitrosoureas and mitomycin).
  • MRI of the brain must be performed at screening for all patients and, if untreated/newly diagnosed brain metastases are identified, the candidate is not eligible. a. The candidate may rescreen for the study after definitive treatment of brain metastases. b. Prior brain metastases treated at least 4 weeks prior to signing the full-study ICF or that are clinically and radiographically stable for at least 1 month prior to Cycle 1, Day 1 and do not require chronic corticosteroid treatment are allowed.
  • Gastrointestinal disorders that will affect oral administration or absorption of TYRA-300.
  • Known history of human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection. a. Participants with a history of HIV on antiviral therapy with undetectable viral load by polymerase chain reaction (PCR) are allowed. b. Participants with a history of hepatitis B virus infection with positive hepatitis B surface antibody, or positive hepatitis B core antibody with a negative PCR test, are allowed. i. Participants positive for hepatitis B surface antibody, who have received the HBV vaccine, have no history of HBV infection, and who are negative for hepatitis B core antibody are allowed. c. Participants with hepatitis C infection previously treated with antiviral therapy and negative for hepatitis C virus by PCR are allowed.
  • History of a second primary malignancy within 3 years of signing the ICF (except definitively treated early-stage cancer such as resected skin cancers and/or completely resected prostate cancer).
  • Known allergy to TYRA-300 or any excipients of the formulated product.
See the full eligibility criteria
Who can join
  • PHASE 1 PART A (1-10): Male and female participants who are 18 years of age or older on the day of signing the ICF.
  • Coronavirus disease 2019 (COVID-19) testing per local standards and regulations, and fulfills COVID-19 vaccination requirements as per local site regulations (if any). Participants with a positive test result for COVID-19 infection at Screening who fulfil all other study eligibility criteria can be rescreened following test normalization and clinical recovery.
  • PHASE 1 PART B (11-20): Male and female participants who are 18 years of age or older on the day of signing the ICF.
  • Life expectancy >12 weeks.
  • Ability to understand and sign the ICF and comply with study procedures.
  • ECOG PS ≤1.
  • Participants with any histologically confirmed advanced solid tumor who have exhausted standard therapeutic options. a. The tumor must have an eligible FGFR3 gene mutation or fusion (see Appendix 14.3.1 and 14.3.2) diagnosed by any authorized/approved or validated local test performed in a CLIA-certified (or regional equivalent) laboratory. i. When tissue is not available to perform a validated local test at a CLIA-certified (or regional equivalent) laboratory, and prior NGS testing has not been performed, a central test, performed at a CLIA-certified laboratory, or a locally validated or approved assay, may be used to identify eligible mutations in ctDNA in plasma. b. A specimen must be submitted for analysis for central ctDNA testing, but the results of the test do not need to be available before starting TYRA-300. c. Any number of prior therapies, including prior FGFR inhibitors, are permitted. d. The BID dose cohorts opened in Part B will enroll participants with locally advanced/metastatic FGFR3 mutation positive urothelial carcinoma who have not received a prior FGFR inhibitor. Participants with metastatic urothelial carcinoma who have received a prior FGFR inhibitor and have an eligible FGFR3 resistance mutation, or participants with other solid tumors with eligible FGFR3 alterations, may be enrolled with medical monitor approval.
  • Ability to swallow oral formulations.
  • At least 1 measurable lesion by RECIST v1.1.
  • Adequate organ and bone marrow function as demonstrated by the following: a. ANC ≥1500/mm3. b. Platelet count ≥75,000/mm3. c. INR ≤1.5 × ULN. i. Participants treated with anticoagulants (eg, warfarin or heparin) will be allowed to participate provided no prior evidence of an underlying abnormality in these parameters exists. Close monitoring of at least weekly evaluations will be performed until INR is stable based on a predose measurement as defined by the local standard of care. d. Total bilirubin ≤1.5 × ULN. Documented Gilbert syndrome is allowed if total bilirubin is mildly elevated (<6 mg/dL). e. ALT and AST ≤2.5 × ULN (≤3 × ULN for participants with liver involvement of their cancer). f. Serum albumin >2 g/dL. g. GFR ≥45 mL/min/1.73 m2 either directly measured via 24-hour urine collection or calculated using CKD-EPI formula for adults.
  • Participants and their partners should practice contraception and reproduction restrictions of the study, as follows: a. Female participants of non-childbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy; or chemically sterile; or ≥12 months of amenorrhea in the absence of chemotherapy, anti-estrogens, or ovarian suppression) do not need to undergo pregnancy testing. b. Female participants of child-bearing potential must have a documented negative pregnancy test within 7 days prior to starting TYRA-300. c. Female participants of child-bearing potential and all male participants must agree to use highly effective contraception prior to study entry and up to 180 days after the last dose of TYRA-300.
  • Life expectancy >12 weeks.
  • COVID-19 testing per local standards and regulations, and fulfils COVID-19 vaccination requirements as per local site regulations (if any). Participants with a positive test result for COVID-19 infection at Screening who fulfil all other study eligibility criteria can be rescreened following test normalization and clinical recovery.
  • PHASE 2 (21-30): Male and female participants who are 18 years of age or older on the day of signing the ICF.
  • Life expectancy >12 weeks.
  • Ability to understand and willingness to sign the ICF.
  • ECOG PS 0 to 2.
  • Participants must have a histologically confirmed locally advanced/metastatic tumor in 1 of the following categories: a. 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 likely to respond to TYRA-300 identified using an FDA authorized/approved CDx or a validated local test performed in a CLIA-certified (or regional equivalent) laboratory. When tissue to perform a validated local test (at a CLIA or regional equivalent certified laboratory) is not available, a central laboratory assay, performed at a CLIA-certified laboratory, or locally validated or approved assay, may be used to identify eligible mutations in ctDNA in plasma. b. Urothelial carcinoma with an eligible FGFR3 gene mutation or rearrangement identified by an FDA authorized/approved CDx or a CLIA (or regional equivalent) validated local test performed in a certified laboratory, who has not received a prior FGFR inhibitor. When tissue to perform a validated local test (at a CLIA or regional equivalent certified laboratory) is not available, a central laboratory assay, or a locally validated or approved assay, may be used to identify eligible mutations in ctDNA in plasma. c. Any solid tumor with an eligible FGFR3 gene mutation or rearrangement identified via an authorized/approved or validated local test in a CLIA-certified (or regional equivalent) laboratory. i. With medical monitor approval, participants who progressed on a prior FGFR inhibitor may be enrolled if they have a documented FGFR3 resistance mutation or other kinase domain mutation for which TYRA-300 is likely to be active based on preclinical studies. Note for France only: Participants with metastatic urothelial carcinoma should have previously received approved therapies, including platinum-based chemotherapy, an immune checkpoint inhibitor, and an antibody-drug conjugate. Participants with metastatic urothelial carcinoma may also be enrolled if they are not candidates for any of the approved therapies. Participants with other tumor types should either have received approved standard therapies for their tumor type or not be candidates for such therapies. Note for Spain only: Participants with metastatic urothelial carcinoma should have previously received approved therapies, including platinum-based chemotherapy, an immune checkpoint inhibitor, and an antibody-drug conjugate. Participants with metastatic urothelial carcinoma may also be enrolled if they are not candidates for any of the approved therapies or if they refuse these therapies. Participants with other tumor types should either have received approved standard therapies for their tumor type, not be candidates for such therapies, or have refused these therapies.
  • Ability to swallow oral formulations.
  • At least 1 measurable lesion by RECIST v1.1.
  • Adequate organ and bone marrow function as demonstrated by the following: a. ANC ≥1500/mm3. b. Platelet count ≥75,000/mm3. c. INR ≤1.5 × ULN. i. Participants treated with anticoagulants (eg, warfarin or heparin) will be allowed to participate provided no prior evidence of an underlying abnormality in these parameters exists. Close monitoring of at least weekly evaluations will be performed until INR is stable based on a predose measurement as defined by the local standard of care. d. Total bilirubin ≤1.5 × ULN. Documented Gilbert syndrome is allowed if total bilirubin is mildly elevated (<6 mg/dL). e. ALT and AST ≤2.5 × ULN (≤3 × ULN for participants with liver involvement of their cancer). f. Serum albumin >2 g/dL. g. GFR ≥45 mL/min/1.73 m2 either directly measured via 24-hour urine collection or calculated using the CKD-EPI formula for adults.
  • Participants and their partners should practice contraception and reproduction restrictions of the study, as follows: a. Female participants of non-childbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy; or chemically sterile; or ≥12 months of amenorrhea in the absence of chemotherapy, anti-estrogens, or ovarian suppression) do not need to undergo pregnancy testing. b. Female participants of child-bearing potential must have a documented negative pregnancy test within 7 days prior to starting TYRA-300. c. Female participants of child-bearing potential and all male participants must agree to use highly effective contraception prior to study entry and up to 180 days after the last dose of TYRA-300.
  • Ability to understand and sign the ICF and comply with study procedures.
  • COVID-19 testing per local standards and regulations, and fulfils COVID-19 vaccination requirements as per local site regulations (if any). Participants with a positive test result for COVID-19 infection at Screening who fulfil all other study eligibility criteria can be rescreened following test normalization and clinical recovery.
  • ECOG PS ≤1.
  • Participants with any histologically confirmed advanced solid tumor who have exhausted standard therapeutic options. For doses of TYRA-300 above 120 mg QD or BID dose levels, participants must have an eligible FGFR3 gene mutation or fusion (see Appendix 14.3.1 and 14.3.2) diagnosed by any authorized/approved or validated local test performed in a CLIA-certified (or regional equivalent) laboratory.
  • Ability to swallow oral formulations.
  • Disease evaluable by RECIST v1.1.
  • Adequate organ and bone marrow function as demonstrated by the following: a. Absolute neutrophil count (ANC) ≥1500/mm3. b. Platelet count ≥75,000/mm3. c. International normalized ratio (INR) ≤1.5 × upper limit of normal (ULN). i. Participants treated with anticoagulants (eg, warfarin or heparin) will be allowed to participate provided no prior evidence of an underlying abnormality in these parameters exists. Close monitoring of at least weekly evaluations will be performed until INR is stable based on a predose measurement as defined by the local standard of care. d. Total bilirubin ≤1.5 × ULN. Documented Gilbert syndrome is allowed if total bilirubin is mildly elevated (<6 mg/dL). e. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN (≤3 × ULN for participants with liver involvement of their cancer). f. Serum albumin >2 g/dL. g. Glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2 either directly measured via 24-hour urine collection or calculated using the CKD-EPI formula for adults.
  • Participants and their partners should practice contraception and reproduction restrictions of the study, as follows: a. Female participants of non-childbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy; or chemically sterile; or ≥12 months of amenorrhea in the absence of chemotherapy, anti-estrogens, or ovarian suppression) do not need to undergo pregnancy testing. b. Female participants of child-bearing potential must have a documented negative pregnancy test within 7 days prior to starting TYRA-300. c. Female participants of child-bearing potential and all male participants must agree to use highly effective contraception prior to study entry and up to 180 days after the last dose of TYRA-300.
What rules you out
  • Participant received chemotherapy, targeted therapy, immunotherapy, or an investigational therapy within 4 weeks or 5 half-lives, whichever is shorter, before the first dose of study drug (within 6 weeks for nitrosoureas and mitomycin).
  • MRI of the brain must be performed at screening for all patients and, if untreated/newly diagnosed brain metastases are identified, the candidate is not eligible. a. The candidate may rescreen for the study after definitive treatment of brain metastases. b. Prior brain metastases treated at least 4 weeks prior to signing the full-study ICF or that are clinically and radiographically stable for at least 1 month prior to Cycle 1, Day 1 and do not require chronic corticosteroid treatment are allowed.
  • Gastrointestinal disorders that will affect oral administration or absorption of TYRA-300.
  • Known history of human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection. a. Participants with a history of HIV on antiviral therapy with undetectable viral load by polymerase chain reaction (PCR) are allowed. b. Participants with a history of hepatitis B virus infection with positive hepatitis B surface antibody, or positive hepatitis B core antibody with a negative PCR test, are allowed. i. Participants positive for hepatitis B surface antibody, who have received the HBV vaccine, have no history of HBV infection, and who are negative for hepatitis B core antibody are allowed. c. Participants with hepatitis C infection previously treated with antiviral therapy and negative for hepatitis C virus by PCR are allowed.
  • History of a second primary malignancy within 3 years of signing the ICF (except definitively treated early-stage cancer such as resected skin cancers and/or completely resected prostate cancer).
  • Known allergy to TYRA-300 or any excipients of the formulated product.
  • Participants taking strong inhibitors and/or inducers of CYP3A4 enzymes are prohibited. a. Participants who can switch to a similar medication without a CYP3A4 interaction will require a washout period of 2 weeks prior to starting TYRA-300.
  • Participant discontinued a prior anti-FGFR therapy due to significant toxicity, defined as hepatotoxicity ≥Grade 3 or any Grade 4 toxicity according to Common Terminology Criteria for Adverse Events v5.0.
  • Participant has not recovered from reversible toxicity of prior anticancer therapy (except toxicities that are not clinically significant including, but not limited to, alopecia, skin discoloration, or Grade 1 neuropathy).
  • Had major surgery within 4 weeks prior to enrollment.
  • Any reason that, in the view of the investigator, would substantially impair the ability of the participant to comply with study procedures and increase the risk to the participant. Examples include poorly controlled diabetes (glycated hemoglobin [HbA1c] >8%) and ongoing active infection requiring intravenous (IV) antibiotics.
  • Females who are pregnant, breastfeeding, or planning to become pregnant within 180 days after the last dose of TYRA-300 and males who plan to father a child while enrolled in this study or within 180 days after the last dose of TYRA-300.
  • Has impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, known gastric ulcers, or unhealed incisions.
  • Has a serum phosphorus level >ULN during screening (within 14 days of treatment and prior to Cycle 1, Day 1) that remains >ULN despite medical management with phosphate binders.
  • Any ocular condition likely to increase the risk of eye toxicity, including: a. History of or current evidence of central serous retinopathy (CSR; including ≥Grade 2 CSR while receiving a prior FGFR inhibitor) or retinal vascular occlusion (RVO). b. Active wet, age-related macular degeneration (AMD). c. Diabetic retinopathy with macular edema. d. Uncontrolled glaucoma (per local standard of care).
  • History of or current uncontrolled cardiovascular disease including: a. Unstable angina, myocardial infarction, or known congestive heart failure Class II to IV within the preceding 12 months. b. Cerebrovascular accident or transient ischemic attack within the preceding 3 months. c. Pulmonary embolism within the preceding 2 months.

The study team makes the final eligibility decision.

Where it's taking place

  • United States
  • Australia

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include United States; Australia. Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.