A Phase 2, Open-Label, Randomized Study of Livmoniplimab in Combination With Budigalimab Versus Chemotherapy in Subjects With Metastatic Urothelial Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 150
- 试验地点
- 37
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
Urothelial carcinoma (UC) is the ninth most common cancer type worldwide. While the treatment of front-line metastatic urothelial carcinoma (mUC) has improved, there remains a high unmet need for effective therapies for participants who have recurrent disease and disease that has progressed after frontline treatment. The purpose of this study is to evaluate the optimized dose, adverse events, and efficacy of livmoniplimab in combination with budigalimab.
Livmoniplimab is an investigational drug being developed for the treatment of mUC. There are 3 treatment arms in this study and participants will be randomized in a 1:1:1 ratio. Participants will either receive livmoniplimab (at one of 2 different doses) in combination with budigalimab (another investigational drug), or either docetaxel, paclitaxel, or gemcitabine (based on investigator's choice). Approximately 150 adult participants will be enrolled in the study across 56 sites worldwide.
In arm 1, participants will receive intravenously (IV) infused livmoniplimab (dose A) in combination with IV infused budigalimab. In arm 2, participants will receive IV infused livmoniplimab (dose B) in combination with IV infused budigalimab. In arm 3 (control), participants will receive the investigator's choice: IV infused or injected docetaxel; IV infused or injected paclitaxel; or IV infused gemcitabine. The estimated duration of the study is up to approximately 3.5 years.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, questionnaires, and scans.
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
- •Participant has histologically or cytologically confirmed urothelial carcinoma (i.e., cancer of the bladder, renal pelvis, ureter, or urethra). Mixed histologic types are allowed if urothelial (transitional cell) is the predominant histology.
- •Participant has radiologically documented metastatic disease.
- •Participant must have experienced radiographic progression or relapse on checkpoint inhibitor (anti-programmed cell death protein 1 [PD-1] or anti-programmed death-ligand 1 [PD-L1]) in the metastatic, adjuvant, or neo-adjuvant setting. Participant must have received at least 2 cycles of anti-PD-1 or anti-PD-L
- •Participants eligible for platinum must have received a platinum containing regimen (cisplatin or carboplatin) in the metastatic, locally advanced, neoadjuvant, or adjuvant setting. If platinum was administered in the neoadjuvant or adjuvant setting, participant must have progressed within 6 months of completion of treatment. Platinum ineligible participants may enroll in this study without receiving a platinum containing regimen.
- •Participant has at least 1 measurable lesion per response evaluation criteria in solid tumors (RECIST) v1.1 as determined by investigator.
- •Life expectancy must be at least 3 months.
排除标准
- •Participant has received more than 1 prior chemotherapy regimen for urothelial cancer in metastatic setting, including chemotherapy agents planned in comparator arm.
- •Platinum based chemotherapy administered in adjuvant or neoadjuvant setting will count towards this criterion if participant progressed within 6 months of completion.
- •Chemotherapy administered during concurrent chemoradiotherapy for primary cancer will not count towards this criterion.
- •The substitution of carboplatin for cisplatin does not constitute a new regimen provided no new chemotherapeutic agents were added to the regimen and no progression was noted prior to the change in platinum.
- •Antibody-drug conjugate (ADC) will not count towards this criterion.
- •Participant who previously received gemcitabine in combination with platinum in metastatic setting will be eligible to receive docetaxel or paclitaxel in comparator arm.
- •Participant has received more than 1 antibody-drug conjugate (ADC) in metastatic setting.
- •Has had prior radiation therapy within 28 days prior to first dose of study drug or who has not recovered (i.e., <= Grade 1 or at baseline) from adverse events due to radiotherapy.
- •History of additional malignancy or history of prior malignancy, except for adequately treated basal or squamous skin cancer, or cervical carcinoma in situ without evidence of disease, or malignancy treated with curative intent and with no evidence of disease recurrence for 5 years since the initiation of that therapy.
- •Prior allogeneic stem cell or solid organ transplantation.
研究组 & 干预措施
Arm 3: Docetaxel, Paclitaxel, or Gemcitabine
Participants will receive docetaxel, paclitaxel, or gemcitabine, investigator's choice, as part of the approximately 3.5 years study duration.
干预措施: Paclitaxel (Drug)
Arm 1: Livmoniplimab (Dose A) + Budigalimab
Participants will receive livmoniplimab (dose A) in combination with budigalimab, as part of the approximately 3.5 years study duration.
干预措施: Livmoniplimab (Drug)
Arm 1: Livmoniplimab (Dose A) + Budigalimab
Participants will receive livmoniplimab (dose A) in combination with budigalimab, as part of the approximately 3.5 years study duration.
干预措施: Budigalimab (Drug)
Arm 2: Livmoniplimab (Dose B) + Budigalimab
Participants will receive livmoniplimab (dose B) in combination with budigalimab, as part of the approximately 3.5 years study duration.
干预措施: Livmoniplimab (Drug)
Arm 2: Livmoniplimab (Dose B) + Budigalimab
Participants will receive livmoniplimab (dose B) in combination with budigalimab, as part of the approximately 3.5 years study duration.
干预措施: Budigalimab (Drug)
Arm 3: Docetaxel, Paclitaxel, or Gemcitabine
Participants will receive docetaxel, paclitaxel, or gemcitabine, investigator's choice, as part of the approximately 3.5 years study duration.
干预措施: Docetaxel (Drug)
Arm 3: Docetaxel, Paclitaxel, or Gemcitabine
Participants will receive docetaxel, paclitaxel, or gemcitabine, investigator's choice, as part of the approximately 3.5 years study duration.
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: Up to Approximately 3.5 Years
OS is defined as the time measured from randomization until death from any cause.
次要结局
- Progression-Free survival (PFS)(Up to Approximately 3.5 Years)
- Best Overall Response (BOR) per Investigator(Up to Approximately 3.5 Years)
- Duration of Response (DOR) per Investigator(Up to Approximately 3.5 Years)
- Percentage of Participants with Adverse Events (AE)s(Up to Approximately 3.5 Years)
- Percentage of Participants with Serious Adverse Events (SAE)s(Up to Approximately 3.5 Years)
- Percentage of Participants with Treatment Emergent Adverse Events (TEAE)s(Up to Approximately 3.5 Years)
- Percentage of Participants with Clinically Significant Vital Sign Measurements as Assessed by the Investigator(Up to Approximately 3.5 Years)
- Percentage of Participants with Clinically Significant Laboratory Values(Up to Approximately 3.5 Years)
- Percentage of Participants with Immune-Related Reactions as AEs of Special Interest(Up to Approximately 3.5 Years)
- Maximum Observed Serum Concentration (Cmax) of Livmoniplimab(Up to Approximately 3.5 Years)
- Cmax of Budigalimab(Up to Approximately 3.5 Years)
- Time to Reach Cmax (Tmax) of Livmoniplimab(Up to Approximately 3.5 Years)
- Tmax of Budigalimab(Up to Approximately 3.5 Years)
- Area Under the Serum Concentration Versus Time Curve (AUC) of Livmoniplimab(Up to Approximately 3.5 Years)
- AUC of Budigalimab(Up to Approximately 3.5 Years)
- Clearance (CL) of Livmoniplimab(Up to Approximately 3.5 Years)
- CL of Budigalimab(Up to Approximately 3.5 Years)
- Volume of Distribution (Vd) of Livmoniplimab(Up to Approximately 3.5 Years)
- Vd of Budigalimab(Up to Approximately 3.5 Years)
- Incidence of Anti-Drug Antibodies (ADAs) of Livmoniplimab(Up to Approximately 3.5 Years)
- ADAs of Budigalimab(Up to Approximately 3.5 Years)
- Incidences of Neutralizing Anti-Drug Antibodies (nADAs) of Livmoniplimab(Up to Approximately 3.5 Years)
- Incidences of nADAs of Budigalimab(Up to Approximately 3.5 Years)