An Exploratory Clinical Study of the Safety and Preliminary Efficacy of Rimegepant Plus Toripalimab in Patients With Advanced Urothelial Carcinoma Following Failure of Standard Therapy
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Incidence of dose-limiting toxicities (DLTs)
研究概览
简要总结
This multicenter, open-label, single-arm exploratory study will evaluate the safety, tolerability, and preliminary antitumor activity of rimegepant in combination with toripalimab in patients with locally advanced or metastatic urothelial carcinoma after failure of prior standard therapy. Approximately 6 to 12 participants will be enrolled. The primary objectives are to assess dose-limiting toxicities and other safety outcomes and to determine the recommended Phase 2 dose (RP2D) of rimegepant when combined with toripalimab. The study will also explore preliminary antitumor activity and selected biomarkers, including changes in the tumor immune microenvironment and circulating tumor DNA. The study is designed to determine whether targeting calcitonin gene-related peptide (CGRP) signaling with rimegepant can be safely combined with programmed cell death protein 1 (PD-1) blockade using toripalimab and whether this combination shows evidence of antitumor activity in patients with advanced urothelial carcinoma who have progressed after standard treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •The participant voluntarily agrees to participate in this study, provides written informed consent, and is willing and able to comply with all study visits and the treatment plan.
- •Male or female participants aged ≥18 years.
- •Histologic or cytologic confirmation of locally advanced or metastatic urothelial carcinoma.
- •The participant's most recent standard therapy must have failed, and disease progression during or after treatment must be radiographically confirmed.
- •Standard therapies include, but are not limited to, platinum-containing chemotherapy regimens; programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitor monotherapy; or a PD-1/PD-L1 inhibitor in combination with chemotherapy or an antibody-drug conjugate (ADC).
- •Participants previously treated with a PD-1/PD-L1 inhibitor may be enrolled, except those who permanently discontinued such treatment because of an immune-related adverse event.
- •At least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
- •The most recent adequate archival tumor tissue specimen obtained within the previous 12 months must be provided as a formalin-fixed, paraffin-embedded block or serial unstained sections. Fresh tumor biopsies at baseline and at disease progression for exploratory biomarker research are strongly recommended but not required; a participant's decision whether to undergo biopsy will not affect eligibility for the main part of this clinical trial.
- •Estimated life expectancy of at least 6 months.
- •Eastern Cooperative Oncology Group (ECOG) score (PS) of 0 or
- •Adequate major-organ function.
排除标准
- •History of a malignancy other than urothelial carcinoma, except in either of the following circumstances:
- •The prior malignancy was treated with potentially curative therapy and there has been no evidence of disease for 5 years.
- •Successfully resected basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, cervical carcinoma in situ, or another carcinoma in situ.
- •Prior allogeneic stem-cell or solid-organ transplantation.
- •Current or prior congenital or acquired immunodeficiency disorder.
- •Known or suspected allergy to an anti-programmed cell death protein 1 (anti-PD-1) agent, history of hypersensitivity to chimeric or humanized antibodies or fusion proteins, or allergy to any excipient of either investigational product.
- •Other clinically significant abnormalities in clinical status or laboratory test results that, in the investigator's opinion, may affect the safety assessment, such as uncontrolled diabetes mellitus, chronic kidney disease, Grade 2 or higher peripheral neuropathy according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 6.0 (NCI CTCAE v6.0), or thyroid dysfunction.
- •An active or poorly controlled serious infection, including any of the following:
- •Positive for antibodies to human immunodeficiency virus type 1 or 2 (HIV-1/2).
- •Active hepatitis B, defined as hepatitis B surface antigen (HBsAg) positivity or hepatitis B virus (HBV) DNA >2,000 IU/mL accompanied by abnormal liver function.
- •Active hepatitis C, defined as hepatitis C virus (HCV) antibody positivity or HCV RNA ≥10³ copies/mL accompanied by abnormal liver function.
- •Active tuberculosis.
- •Any other uncontrolled active infection of Grade 3 or higher according to NCI CTCAE v6.
- •Failure to recover from surgery, such as the presence of an unhealed incision or serious postoperative complications.
- •Participants who are pregnant or breastfeeding, or female or male participants of reproductive potential who are unwilling or unable to use effective contraception.
- •Any other circumstance that the investigator considers unsuitable for enrollment.
研究组 & 干预措施
Rimegepant plus toripalimab
Participants will receive rimegepant in combination with toripalimab in a dose-escalation design. At dose level 1, rimegepant will be administered orally at 75 mg every other day, together with toripalimab 3 mg/kg by intravenous infusion every 2 weeks. If dose level 1 is considered tolerable according to the prespecified dose-limiting toxicity criteria, enrollment will proceed to dose level 2, in which rimegepant will be administered orally at 75 mg once daily with toripalimab 3 mg/kg every 2 weeks.
干预措施: Rimegepant (Drug)
Rimegepant plus toripalimab
Participants will receive rimegepant in combination with toripalimab in a dose-escalation design. At dose level 1, rimegepant will be administered orally at 75 mg every other day, together with toripalimab 3 mg/kg by intravenous infusion every 2 weeks. If dose level 1 is considered tolerable according to the prespecified dose-limiting toxicity criteria, enrollment will proceed to dose level 2, in which rimegepant will be administered orally at 75 mg once daily with toripalimab 3 mg/kg every 2 weeks.
干预措施: Toripalimab (Biological)
结局指标
主要结局
Incidence of dose-limiting toxicities (DLTs)
时间窗: From the first dose through Day 14
Occurrence of toxicity meeting the prespecified DLT criteria during the DLT observation period;
Recommended Phase 2 dose (RP2D) of rimegepant in combination with toripalimab
时间窗: From first participant enrollment through completion of the dose-escalation phase, up to 8 months
The recommended Phase 2 dose (RP2D) of rimegepant in combination with toripalimab will be determined based primarily on the occurrence of dose-limiting toxicities (DLTs), together with the overall safety and tolerability of the evaluated dose levels.
次要结局
- Incidence and severity of adverse events and serious adverse events(From the first dose through 90 days after the last dose)
- Radiographic progression-free survival (rPFS)(From enrollment until radiographic disease progression or death from any cause, whichever occurs first, up to 6 months)
研究者
Nianzeng Xing
Vice President of the Hospital
Cancer Institute and Hospital, Chinese Academy of Medical Sciences