NCT06995677招募中2 期
A Phase 2 Multicenter, Open-Label Study Evaluating the Efficacy and Safety of TYRA-300 in Participants With FGFR3 Altered Low Grade, Intermediate Risk Non-Muscle Invasive Bladder Cancer (SURF302)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 49
- 主要终点
- To assess the efficacy of TYRA-300 in LG IR-NMIBC participants
研究概览
简要总结
Phase 2 Study of TYRA-300 in FGFR3 Altered Low Grade, Intermediate Risk NMIBC
详细描述
A Phase 2 Multicenter, Open-Label Study Evaluating the Efficacy and Safety of TYRA-300 in Participants with FGFR3 Altered Low Grade, Intermediate Risk Non-Muscle Invasive Bladder Cancer
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants age ≥18 at time of informed consent and willing and able to comply with all required study procedures
- •Able to understand and given written informed consent
- •Participants with histologically confirmed low-grade NMIBC within 8 weeks prior to C1D1 with prior diagnostic biopsy/TURBT to confirm stage and grade and with at least 3 mm and no more than 12 mm total (1/2 a resectoscope loop to 2 loops, refer to Section 8.1.6) residual visible tumor as a marker lesion(s) left behind:
- •Ta low grade
- •T1 low grade
- •Participants must have protocol-defined intermediate risk NMIBC and meet at least one of the following criteria
- •Recurrence within 1 year, LG Ta
- •Solitary LG Ta >3cm
- •LG Ta, multifocal
- •Documented negative voiding urine cytology within 2 weeks of C1D1
- •Documented activating FGFR3 alteration (mutation or fusion)
- •Have undergone bladder mapping and identification of visible marker lesion(s) within 8 weeks prior to C1D1 (refer to Inclusion Criterion #8)
- •No evidence of urothelial carcinoma of the upper urinary tract (confirmed by imaging) or prostatic urethra within 6 months of C1D
- •No prior BCG administration within 3 months of the date of most recent consent.
- •No intravesical chemotherapy within 8 weeks prior to C1D
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1
- •Pathology consistent with pure urothelial carcinoma; if mixed histology, ensure that at least 80% of the sample is urothelial
- •Adequate bone marrow, liver, and renal function as defined as:
- •a. Bone marrow function: i. Absolute neutrophil count (ANC) > or = 1,500/mm3 ii. Platelet count > or = 75,000/mm3 iii. /hemoglobin > or = 10.0 g/dL b. Liver function: i. Total bilirubin < or = ULN ii. Alanine aminotransferase (ALT) < or = ULN iii. Aspartate aminotransferase (AST) < or = ULN c. Renal function: i. estimated glomerular filtration rate >30 mL/min calculated using the modification of diet in renal disease equation or CKD-EPI formula j. Serum Phosphate level < or = ULN d. Coagulation i. International normalized ratio (INR) < or = 1.5 x ULN
- •Ability to swallow tablets
- •Participants (male and female) of child-bearing potential (including females who are post-menopausal for less than 1 year) must be willing to practice effective contraception while on treatment and be willing and able to continue contraception for 3 months (males) and 6 months (females) after the last dose of study treatment. Potential male participants must refrain from donating sperm until 3 months after the last dose of study treatment. Potential male participants should consider the potential impact of TYRA-300 on their ability to father a child and discuss options with the site study staff.
- •Participants who are positive for human immunodeficiency virus (HIV) must have a viral load below the limits of detection and on stable antiretroviral therapy for at least 3 months prior to C1D
- •NOTE: some of the compounds in antiretroviral therapy may be on the prohibited medications list. Allowances will be made to ensure the participant's HIV treatment continues uninterrupted following a discussion with the Sponsor's medical monitor. A discussion of the impact of the antiretroviral therapy on TYRA- 300 needs to be discussed with the potential participant prior to C1D
- •Potential participants with active hepatitis B virus (HBV) infection should be on a suppressive antiviral therapy prior to C1D
- •Note: participants with no history of chronic HBC infection do not need serology testing at Screening.
- •Participants with a history of hepatitis C virus (HCV) infection should have completed curative antiviral treatment or be on stable treatment and must have a HCV viral load below the limit of quantification. Note: participants with no history of chronic HCV infection do not need serology testing at Screening.
排除标准
- •Current or previous history of muscle invasive bladder cancer
- •Current or previous history of lymph node positive and/or metastatic bladder cancer
- •Evidence of pure squamous cell carcinoma, pure adenocarcinoma or pure undifferentiated carcinoma of the bladder
- •Currently receiving systemic cancer therapy (cytotoxic, immunotherapy, targeted)
- •Currently receiving treatment with a prohibited therapy
- •Current or prior history of pelvic external beam radiotherapy for bladder cancer
- •Current or history of receiving a prior FGFR inhibitor
- •Systemic immunotherapy for treatment of cancer within 6 months prior to C1D1
- •Treatment with an investigational agent within 30 days or 5 half-lives from C1D1, whichever is shorter; compounds with an unknown half-life will default to the 30 days.
- •Prior treatment with an intravesical agent within 8 weeks prior to C1D1
- •Current ongoing toxicity from a previous bladder cancer therapy or any toxicity that would impact the interpretability of study results per the Investigator's discretion.
- •Had major surgery within 4 weeks prior to C1D1
- •Any reason that in the view of the investigator, would substantially impair the ability of the participant to comply with study procedures and/or risk to the participant (i.e., uncontrolled diabetes)
- •Females who are pregnant, breastfeeding or planning to become pregnant within 6 months after the last dose of TYRA-300 and males who plan to father a child while enrolled in this study or within 3 months after the last dose of TYRA-300
- •Has impaired wound healing capacity
- •Serum phosphate levels above the upper limit of normal during screening
- •Any ocular condition likely to increase the risk of eye toxicity
- •Current evidence of central serous retinopathy or retinal pigmented epithelial detachment of any grade at time of baseline examination during Screening as well as any active ocular abnormality at baseline (during Screening) that may increase the chance of ocular toxicity.
- •History of or current uncontrolled cardiovascular disease
- •Gastrointestinal disorders that will affect oral administration or absorption of TYRA-300
- •Other malignancy within 3 years of signing ICF, except for skin cancer (e.g. basal cell, squamous cell, melanoma in situ with negative margins) and cured and/or active surveillance malignancies (i.e., prostate, breast, and others in consultation with the Sponsor).
- •Known allergy to TYRA-300 or any excipients of the formulated product
- •Participants taking moderate and strong inhibitors and/or inducers of CYP3A4 enzyme and inhibitors of P-gp and BCRP.
- •History of prolonged QT syndrome or baseline heart rate-corrected QT interval using Fridericia formula (QTcF) interval >470 ms
研究组 & 干预措施
Possible Dose Cohort C (DCC)
Experimental
TYRA-300 monotherapy in Participants with FGFR3 Altered Low Grade, Intermediate Risk Non-Muscle Invasive Bladder Cancer
干预措施: TYRA-300 Dose 70 mg (Drug)
Dose Cohort A (DCA)
Experimental
TYRA-300 monotherapy in Participants with FGFR3 Altered Low Grade, Intermediate Risk Non-Muscle Invasive Bladder Cancer
干预措施: TYRA-300 60mg (Drug)
Dose Cohort B (DCB)
Experimental
TYRA-300 monotherapy in Participants with FGFR3 Altered Low Grade, Intermediate Risk Non-Muscle Invasive Bladder Cancer
干预措施: TYRA-300 50mg (Drug)
结局指标
主要结局
To assess the efficacy of TYRA-300 in LG IR-NMIBC participants
时间窗: at 3 months
Complete response (CR) rate at 3 months
次要结局
- Overall CR rate(From the start of study treatment up to 24 months)
- Overall response rate (ORR)(From the start of study treatment up to 24 months)
- Duration of complete response (DOCR) (responders only)(Time from initial CR to confirmed recurrence of disease, progression of disease, development of extravesical disease, or death from any cause, whichever comes first, up to 24 months.)
- Duration of response DOR (responders only)(Time from initial response of CR or partial response to confirmed recurrence of disease, progression of disease, development of extravesical disease, or death, from any cause, up to 24 months)
- Time to recurrence (responders only)(Time from start of response to confirmed recurrence of disease or development of extravesical disease, up to 24 months)
- Recurrence-free rate (responders only)(at 12 months and 24 months)
- Duration of response (responders only)(time from initial response to confirmed recurrence of disease or death, up to 24 months)
- Time to recurrence (responders only)(time from start of response to confirmed recurrence of disease, up to 24 months)
- Recurrence-free survival rate (responders only)(at 12 months and 24 months)
- Progression-free survival (all participants)(time from randomization to the progression of disease or death from any cause, whichever occurs first, up to 24 months)
- Incidence and severity of adverse events(Up to 2 years)
- To assess the safety and tolerability of TYRA-300 in LG IR-NMIBC participants(From initiation of treatment to 2 years)
研究者
研究点 (49)
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