This is a Phase I open, multi-center, first-in-human study evaluating JSKN016 in subjects with advanced metastatic solid tumors, divided into dose escalation and dose extension.
1. Subjects can understand the informed consent form, voluntarily participate in and sign the informed consent form; 2. The subjects were ≥18 years old on the day of signing the informed consent, male or female; 3. Subjects with histologically and/or cytologically confirmed advanced unresectable or metastatic epithelial malignancies that have failed or are intolerable to previous standard therapies, preferentially but not limited to the following types: AGA-positive non-small cell lung cancer, HER2 IHC 0 breast cancer, etc.
For the enrolled subjects, the above driver gene mutations were not tested, but the previous test results confirmed by the investigators were accepted;
If only EGFR overexpression without driver gene mutation can not be included;
Prior osimertinib therapy is required if EGFR T790M mutation is present;
1. Patients with symptoms of active central nervous system metastases, except those with stable parenchymal brain metastases as assessed by investigators, were defined as seizure-free for more than 12 weeks with or without the use of antiepileptic drugs; No need for glucocorticoids; At least one MRI showed that the patient was stable on imaging. Or stable after treatment for more than 1 month without symptoms; 2. Received any investigational drug within 28 days before dosing; 3. Receipt of other antineoplastic therapy within 28 days before dose or within 5 half-lives of previous antineoplastic drugs, whichever is shorter but requires a minimum of 14 days; Received Chinese herbal medicine with clear anti-tumor indications within 14 days before drug administration; 4. Local palliative treatment within 14 days before administration; 5. Major surgical treatment (such as transabdominal or transthoracic surgery) within 28 days before drug administration; Excluding minor procedures such as diagnostic punctures or infusion device implantation or biliary stenting) or anticipated need for major surgical treatment during the study period; 6. Gastrointestinal abnormalities with obvious clinical manifestations, including but not limited to: intestinal obstruction or the presence of symptoms and signs of intestinal obstruction within 6 months before drug administration, but if the obstruction was completely removed after surgical treatment, screening could be performed (patients with previous intestinal stent implantation and the intestinal stent was not removed during the screening period were not allowed); Patients with gastrointestinal perforation, gastrointestinal fistula, intra-abdominal abscess and non-gastrointestinal fistula (such as tracheoesophageal fistula) within 6 months before administration; Patients with gastrointestinal bleeding (CTCAE≥ grade 3) within 6 months before treatment, or gastrointestinal bleeding (melena, bloody stool, etc.) within 1 month before randomization were eligible if hemorrhoid bleeding was confirmed or only showed positive fecal occult blood.
Active HBV or HCV infection Patients with HBsAg (+) and HBV-DNA< 2500 copies /mL or 500 IU/mL were allowed to be enrolled. HCV-Ab (+) and HCV-RNA negative were allowed to enroll.
HIV infection;
Known active tuberculosis; Active syphilis;
Single group
JSKN016 injection
DrugJSKN016 is a bispecific antibody drug conjugate targeting HER3 and TROP2.
Incidence of DLTs
DLTs are defined as one or more serious toxic reactions that occur within 21 days (Q3W) after the start of dosing and are determined to be reasonably associated with the study drug
The frequency and severity of treatment-related adverse events (TEAE), treatment-related adverse events (TRAE), and serious adverse events (SAE).
Clinically significant changes in lab test findings
MTD or RP2D of JSKN 016
To determinate MTD and/ or RP2D of JSKN016
Objective Response Rate (ORR) in Extended queue
Objective response rate (ORR) was defined as the proportion of participants who achieve either complete response \[CR\] or partial response \[PR\] per Response Evaluation Criteria in Solid Tumors (RECIST v1.1）
Clinical benefit rates (CBR)
Clinical benefit rate (CR+PR+\[stable disease (SD) ≥ 6 months\]) is defined as those participants with best response as CR or PR or else SD with a duration of at least 6 months. SD for 6 months duration was defined as the time from the first dose to the first documentation of PD or to the last adequate response assessment prior to data cut-off date, whichever is earlier.
Cmax of JSKN016
Maximum (Peak) Observed blood Concentration (Cmax) of JSKN016 Following First Dose
Tmax of JSKN016
Time of Maximum blood Concentration (Tmax) of JSKN016 Following First Dose
AUC of JSKN016
The blood PK parameters of JSKN016 and its analytes for area under the concentration-versus-time curve from time 0 to the last quantifiable concentration as calculated by the linear-up log-down trapezoidal method (AUClast) and AUC from time 0 to infinity (AUCinf) elimination rate constant associated with the terminal phase were estimated using standard non-compartmental methods.
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