A Phase I/II, Multi-center, Open Label Study of DYP688 in Patients With Metastatic Uveal Melanoma (MUM) and Other GNAQ/11 Mutant Melanomas
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 66
- 试验地点
- 11
- 主要终点
- Phase II: Overall Response rate (ORR) per RECIST 1.1
研究概览
简要总结
This is a FIH, phase I/II, open label, multi-center study of DYP688 as a single agent. The purpose of this study is to characterize the safety, tolerability, and anti-tumor activity of DYP688 as a single agent in patients with metastatic uveal melanoma (MUM) and other melanomas harboring GNAQ/11 mutations.
详细描述
This is a First in Human (FIH), phase I/II, open label, multi-center study of DYP688 as a single agent. There will be two parts to this study: a phase I, dose escalation part followed by a phase II part. Dose escalation will be conducted in patients with MUM and other melanomas harboring GNAQ/11 mutations. Once the MTD and/or RD(s) is determined in the dose escalation part, the study may continue with a phase II part. The phase II part will be conducted in two groups of patients with MUM, a prior tebentafusp-treated group and a tebentafusp-naïve group. In addition to MUM, a third group of patients with non-uveal GNAQ/11 mutant melanomas may also be explored. This cohort may be opened based on emerging data from the dose escalation part of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients in the dose escalation part must be ≥ 18 years of age at the time of informed consent (ICF) signature. In the phase II part, patients ≥ 12 years of age at the time of informed consent may be eligible for enrollment (not applicable in countries where enrollment is restricted by the local health authority to patients ≥ 18 years of age). Patients must have a minimum weight of 40 kg.
- •ECOG performance status ≤ 1 for patients ≥ 18 years of age; Karnofsky performance status ≥ 70 for patients ≥ 16 and < 18 years of age; Lansky performance status ≥ 70 for patients ≥ 12 and < 16 years of age
- •Patients must be suitable and willing to undergo study required biopsies according to the treating institution's own guidelines and requirements. If a biopsy is not medically feasible, exceptions may be considered after documented discussion with Novartis.
- •For all patients in Dose Escalation
- •MUM: uveal melanoma with histologically or cytologically confirmed metastatic disease. Patient must be either treatment naive or have received any number of prior lines and progressed on most recent therapy
- •Non-MUM: advanced cutaneous or mucosal melanoma with histologically or cytologically confirmed metastatic disease that has progressed following all standard therapies or that has no satisfactory alternative therapies and has evidence of GNAQ/11 mutation based on local data
- •For patients in Phase II
- •Tebentafusp naïve group: Diagnosis of uveal melanoma with histologically or cytologically confirmed metastatic disease that has progressed following standard therapies or that has no satisfactory alternative therapies
- •Tebentafusp pre-treated group: Diagnosis of uveal melanoma with histologically or cytologically confirmed metastatic disease. Patients must be previously treated with tebentafusp and have progressed
- •Non-MUM: patients with diagnosis of cutaneous or mucosal melanomas harboring GNAQ/11 mutations based on local data, with histologically or cytologically confirmed metastatic disease that has progressed following all standard therapies or that has no satisfactory alternative therapies
排除标准
- •Malignant disease, other than that being treated in this study.
- •Active brain metastases, i.e. symptomatic brain metastases or known leptomeningeal disease.
- •Evidence of active bleeding or bleeding diathesis or significant coagulopathy (including familial) or a medical condition requiring long term systemic anticoagulation that would interfere with biopsies.
- •History of anaphylactic or other severe hypersensitivity / infusion reactions to ADCs or monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction.
- •Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment within the stated timeframes:
- •2 weeks for fluoropyrimidine therapy
- •4 weeks for radiation therapy or limited field radiation for palliation within ≤ 2 weeks prior to the first dose of study treatment.
- •4 weeks or ≤ 5 half-lives (whichever is shorter) for chemotherapy or biological therapy (including monoclonal antibodies) or continuous or intermittent small molecule therapeutics or any other investigational agent.
- •6 weeks for cytotoxic agents with major delayed toxicities, such as nitrosoureas and mitomycin C.
- •4 weeks for immuno-oncologic therapy, such as CTLA-4, PD-1, or PD-L1 antagonists.
- •Clinically significant and / or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA grade ≥ 2) or clinically significant arrhythmia despite medical treatment.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Phase II: Non-uveal melanoma
Optional Arm: To explore patients with non-uveal melanoma that harbor GNAQ or 11 mutations, based on emerging data from dose escalation
干预措施: DYP688 (Drug)
Phase II: Tebe pre-treated
Patients with metastatic uveal melanoma that have been previously treated with tebentafusp
干预措施: DYP688 (Drug)
Phase I: Dose Escalation
Patients with metastatic uveal melanoma or other GNAQ/11 mutant melanomas
干预措施: DYP688 (Drug)
Phase II: Tebe naive group
Patients with metastatic uveal melanoma that has not received prior treatment with tebentafusp
干预措施: DYP688 (Drug)
结局指标
主要结局
Phase II: Overall Response rate (ORR) per RECIST 1.1
时间窗: 17 months
ORR in Phase II will be evaluated by central review per RECIST 1.1.
Phase I (Dose Escalation): Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
时间窗: 9 months
Assessment of safety of DYP688 as a single agent
Phase I (Dose Escalation): Frequency of dose interruptions, reductions, and discontinuations
时间窗: 9 months
Assessment of tolerability of DYP688 as a single agent
Phase I (Dose Escalation): Incidence and severity of dose limiting toxicities (DLTs) during the first 28 days of treatment.
时间窗: 28 days
A DLT is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, intercurrent illness, or concomitant medications that occurs within the first cycle of treatment with DYP688. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
次要结局
- Phase I and Phase II: PK profile of DYP688 - Area under the concentration-time curve (AUC)(26 months)
- Phase II: Disease Control Rate (DCR) per RECIST v1.1(17 months)
- Phase I and Phase II: PK profile of DYP688 - Peak concentration (Cmax)(26 months)
- Phase I and Phase II: PK profile of DYP688 - Total body clearance (CL)(26 months)
- Phase II: Duration of response (DoR) per RECIST v1.1(17 months)
- Phase I and Phase II: PK profile of DYP688 - Elimination half-life(26 months)
- Phase I and Phase II: Prevalence and incidence of anti-DYP688 antibodies(26 months)
- Phase I (Dose Escalation): Best Overall Response (BOR) per RECIST v1.1(9 months)
- Phase I (Dose Escalation): Overall Response Rate (ORR) per RECIST v1.1(17 months)
- Phase II: Progression free survival (PFS) per RECIST v1.1(17 months)
- Phase II: Overall Survival (OS)(17 months)
- Phase II: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)(17 months)
- Phase II: Frequency of dose interruptions, reductions, and discontinuations(17 months)