2023-509451-14-00招募中2 期
As 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
- 2 期
- 状态
- 招募中
- 入组人数
- 27
- 试验地点
- 5
- 主要终点
- Phase I: Incidence and severity of dose limiting toxicities (DLTs) during the first 28 days of treatment.
研究概览
简要总结
Phase I: to characterize the safety and tolerability and to identify the MTD and/or RD and regimen for future studies of DYP688 as a single agent. Phase II: to evaluate the anti-tumor activity of DYP688 as a single agent.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
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. For the 32 mg/kg dose level, a maximum weight limit of 115 kg may not be exceeded.
- •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 medically feasible.
- •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.
- •For all patients in Dose Escalation 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.
- •For patients in Phase II 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.
- •For patients in Phase II 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 PDL1 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.
结局指标
主要结局
Phase I: Incidence and severity of dose limiting toxicities (DLTs) during the first 28 days of treatment.
Phase I: Incidence and severity of dose limiting toxicities (DLTs) during the first 28 days of treatment.
Phase I: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including changes in laboratory values, electrocardiograms (ECGs), and vital signs.
Phase I: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including changes in laboratory values, electrocardiograms (ECGs), and vital signs.
Phase I: Frequency of dose interruptions, reductions, and discontinuations.
Phase I: Frequency of dose interruptions, reductions, and discontinuations.
Phase II: Overall Response rate (ORR) per RECIST 1.1.
Phase II: Overall Response rate (ORR) per RECIST 1.1.
次要结局
- Phase I and Phase II: PK parameters for total mAb, conjugated active and inactive payload, and unconjugated active payloads (e.g., AUC, Cmax, CL, half-life).
- Phase I: Prevalence and incidence of anti-DYP688 antibodies.
- Phase I: Best Overall Response (BOR).
- Phase I: Overall Response Rate (ORR) per RECIST v1.1.
- Phase II: Duration of response (DoR), progression free survival (PFS) and DCR per RECIST v1.1.
- Phase II: Overall survival (OS)
- Phase II: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including changes in laboratory values, electrocardiograms (ECGs), and vital signs.
- Phase II: Frequency of dose interruptions, reductions, and discontinuations PK parameters for total mAb, conjugated active and inactive payload, and unconjugated active payloads (e.g., AUC, Cmax, CL, half-life).
- Phase II: Prevalence and incidence of anti-DYP688 antibodies.
研究者
Novartis Pharma Arzneimittel GmbH
Scientific
Novartis Pharma AG
研究点 (5)
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