A Multi-center, Open-label Phase II Study to Evaluate the Safety and Efficacy of YH003 in Combination with Toripalimab (anti-PD-1 MAb) in Patients with Unresectable/metastatic Melanoma and Pancreatic Ductal Adenocarcinoma (PDAC)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Confirmed Objective Response Rate (ORR)
研究概览
简要总结
A phase II, multi-center, open-label study to evaluate the safety and efficacy of YH003 in combination with Toripalimab (anti-PD-1 mAb) in patients with unresectable/metastatic melanoma and pancreatic ductal adenocarcinoma (PDAC)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •To be eligible for study entry patients must satisfy all of the following criteria:
- •Subjects must have the ability to understand and willingness to sign a written informed consent document.
- •Histologically or cytologically confirmed unresectable or metastatic melanoma and pancreatic ductal adenocarcinoma
- •Cohort 2A: had confirmed progressive disease during treatment with an anti-PD-1/PD-L1 with or without CTLA-4 therapy.
- •Cohort 2B: had confirmed progressive disease during treatment with first line standard of care chemotherapy per local guideline.
- •Cohort 2C: must not have received any prior systematic treatment, including chemotherapy, biological therapy, or targeted therapy for unresectable locally advanced/ metastatic pancreatic duct adenocarcinoma.
- •Subject must have at least 1 unidimensional measurable disease by RECIST 1.
- •Subjects must be age between 18 years.
- •Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Life expectancy ≥3 months.
- •Subjects must have adequate organ function
排除标准
- •Subjects who meet any of the following criteria cannot be enrolled:
- •Cohort 2A: History of life-threatening toxicity or treatment discontinuation due to related to prior anti-PD-1/PD-L1 with or without CTLA-4 treatment for subjects with unresectable/ metastatic melanoma
- •2.Subjects have another active invasive malignancy within 5 years, with the following exceptions and notes:
- •Previous exposure to TNFR such as anti-CD137, OX40, CD27 and CD357 antibodies.
- •Subjects must not have received any anticancer therapy or another investigational agent within the shorter of 4 weeks or 5 half-lives before the first dose of the study treatment.
- •Subjects with a history of ≥ Grade 3 immune-related adverse events resulted from previous immunotherapy or treatment discontinuation due to previous immunotherapy. .
- •History of clinically significant sensitivity or allergy to monoclonal antibodies and their excipients or known allergies to antibodies produced from Chinese hamster ovary cells, which in the opinion of the Investigator suggests an increased potential for an adverse hypersensitivity to YH003 or Toripalimab. (For cohort 2C: history of severe hypersensitivity reaction to Nap-paclitaxel and/or gemcitabine).
- •Primary central nervous system (CNS) malignancies or symptomatic CNS metastases.
- •History of (non-infectious) pneumonitis that required corticosteroids or current pneumonitis, or history of interstitial lung disease.
- •Active, hemodynamically significant pulmonary embolism within 12 weeks prior to the first dose of study drug.
- •Subjects must not have a known or suspected history of an autoimmune disorder
- •Clinically uncontrolled intercurrent illness,
- •Severe cardiovascular disease including symptomatic congestive heart failure (New York Heart Association class III or IV), unstable angina, uncontrolled hypertension, cardiac arrhythmia, a history of myocardial infarction within 6 months or a history of arterial thromboembolic event and pulmonary embolism within 3 months of the first dose of investigational agent.
- •QTc > 480 ms (Fridericia equation) at baseline; no concomitant medications that would prolong the QT interval; no family history of long QT syndrome.
研究组 & 干预措施
YH003 with Toripalimab in subjects with unresectable /metastatic melanoma
YH003 in combination with Toripalimab in subjects with unresectable /metastatic melanoma after having failed PD-1/L1 +/- CTLA-4 treatment;
干预措施: YH003 (Drug)
YH003 with Toripalimab in subjects with unresectable /metastatic melanoma
YH003 in combination with Toripalimab in subjects with unresectable /metastatic melanoma after having failed PD-1/L1 +/- CTLA-4 treatment;
干预措施: Toripalimab (Drug)
YH003 with Toripalimab in subjects with PDAC
YH003 in combination with Toripalimab in subjects with unresectable/ metastatic pancreatic ductal adenocarcinoma (PDAC) as 2nd line treatment;
干预措施: YH003 (Drug)
YH003 with Toripalimab in subjects with PDAC
YH003 in combination with Toripalimab in subjects with unresectable/ metastatic pancreatic ductal adenocarcinoma (PDAC) as 2nd line treatment;
干预措施: Toripalimab (Drug)
YH003 with Toripalimab plus standard chemotherapy
YH003 in combination with Toripalimab plus standard chemotherapy (Nab-paclitaxel + Gemcitabine) in subjects with unresectable/metastatic PDAC as 1st line treatment;
干预措施: YH003 (Drug)
YH003 with Toripalimab plus standard chemotherapy
YH003 in combination with Toripalimab plus standard chemotherapy (Nab-paclitaxel + Gemcitabine) in subjects with unresectable/metastatic PDAC as 1st line treatment;
干预措施: Toripalimab (Drug)
YH003 with Toripalimab plus standard chemotherapy
YH003 in combination with Toripalimab plus standard chemotherapy (Nab-paclitaxel + Gemcitabine) in subjects with unresectable/metastatic PDAC as 1st line treatment;
干预措施: Nab-paclitaxel (Drug)
YH003 with Toripalimab plus standard chemotherapy
YH003 in combination with Toripalimab plus standard chemotherapy (Nab-paclitaxel + Gemcitabine) in subjects with unresectable/metastatic PDAC as 1st line treatment;
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Confirmed Objective Response Rate (ORR)
时间窗: up to 1 year after the last dosing
Overall Response Rate (ORR) by investigator's assessment according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
次要结局
- Overall survival (OS)(up to 1 year after the last dosing)
- Adverse events (AE)(up to 1 year after the last dosing)
- Disease control rate (DCR)(up to 1 year after the last dosing)
- Duration of disease control (DDC)(up to 1 year after the last dosing)
- Incidence of neutralizing antibodies (NAbs)(up to 1 year after the last dosing)
- Duration of response (DOR)(up to 1 year after the last dosing)
- Time to response (TTR)(up to 1 year after the last dosing)
- Progression free survival (PFS)(up to 1 year after the last dosing)