本研究为第一期/Ib期、开放标签研究。剂量递增部分将评估 DKY709 及 DKY709 联合 PDR001 于曾接受抗 PD-1/PD-L1 治疗的非小细胞肺癌或黑色素瘤受试者，或鼻咽癌受试者中的安全性与耐受性。在确定特定治疗组的 MTD/RD 后，剂量扩展将进一步评估各方案于 MTD/RD 时的安全性、耐受性、PK/PD 及抗肿瘤活性。
适应症：Carcinoma, Non-Small-Cell Lung、Melanoma、Nasopharyngeal Carcinoma、Microsatellite Stable Colorectal Cancer、Triple Negative Breast Cancer
入组条件
纳入标准
- Signed informed consent must be obtained prior to participation in the study.
- Patients must be ≥18 years of age at the time of informed consent form (ICF) signature.
- Patients with advanced/metastatic cancer who have progressed despite having received standard therapy in the metastatic setting or are intolerant to standard therapy, and for whom no effective standard therapy is available
- In expansion: patient with measurable disease as determined by RECIST version 1.1,
- Dose escalation, patients must fit into one of the following groups:
- NSCLC, previously treated with an anti-PD-1/PD-L1 therapy
- Cutaneous Melanoma, previously treated with an anti-PD-1/PD-L1 therapy
- Dose expansion part, patients must fit into one of the following groups:
- NSCLC with historic documentation of PD-L1 ≥ 1%. Patients must have progressive disease after having experienced at least 4 months of investigator-assessed disease stability or response on prior anti-PD-L1-containing therapy
- Cutaneous Melanoma, previously treated with anit-PD-1/PD-L1 therapy. Patients should have documented progression following anti-PD-1/PD-L1 therapy.
- NPC, naive to anti-PD-1/PD-L1 therapy
- mssCRC, naive to anti-PD-1/PD-L1 therapy
- TNBC, naive to anti-PD-1/PD-L1 therapy
- ECOG Performance Status ≤ 1
- Patients must have a site of disease amenable to core needle biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Patients must be willing to undergo a new tumor biopsy at baseline, and during therapy on the study. Exceptions may be considered after documented discussion with Novartis.
排除标准
- Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery), or increasing doses of corticosteroids within 2 weeks prior to study entry. Patients with treated brain metastases should be neurologically stable for at least 4 weeks prior to study entry and off steroids for at least 2 weeks before administration of any study treatment.
- History of severe hypersensitivity reactions to any ingredient of study drug(s) or other mAbs and/or their excipients.
- Patient with out of range laboratory values defined as:
- Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) \< 40 mL/min
- Total bilirubin \> 1.5 x ULN, except for patients with Gilbert's syndrome who are excluded if total bilirubin \> 3.0 x ULN or direct bilirubin \> 1.5 x ULN
- Alanine aminotransferase (ALT) \> 3 x ULN, except for patients that have tumor involvement of the liver, who are excluded if ALT \> 5 x ULN
- Aspartate aminotransferase (AST) \> 3 x ULN, except for patients that have tumor involvement of the liver, who are excluded if AST \> 5 x ULN
- Absolute neutrophil count (ANC) \< 1.0 x 109/L
- Platelet count \< 75 x 109/L (growth factor or transfusion support may not be used to meet entry criterion)
- Hemoglobin (Hgb) \< 8 g/dL (growth factor or transfusion support may not be used to meet entry criterion)
- Magnesium, calcium or phosphate abnormality CTCAE \> grade 1
- Potassium abnormality CTCAE ≥ grade 1; supplementation to meet eligibility criteria is acceptable
- Clinically significant cardiac disease or impaired cardiac function, including any of the following:
- Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA grade ≥ 2), uncontrolled hypertension or clinically significant arrhythmia
- On screening: QTcF \> 450 msec (male), or \> 460 msec (female)
- QTc not assessable
- Congenital long QT syndrome
- History of familial long QT syndrome or known family history of as Torsades de Pointes
- Acute myocardial infarction or unstable angina pectoris \< 3 months prior to study entry
入组条件维持 ClinicalTrials.gov 原始英文登记资料，实际入组资格以研究团队的正式评估与受试者知情同意书为准。资料来源：ClinicalTrials.gov，每两周自动更新，最后同步：2026年10月8日。