Advanced Malignant Solid Tumors
Conditions
Keywords
EGFR/HER3, JSKN021
Brief summary
This is a Phase I, open-label, multi-center, first-in-human (FIH) clinical trial designed to evaluate the safety, tolerability, pharmacokinetic (PK) profiles, and the preliminary antitumor activity of JSKN021 in advanced malignant solid tumors.
Interventions
DRUGJSKN021
JSKN021 administered intravenously at selected dose levels according to protocol
Sponsors
Jiangsu Alphamab Biopharmaceuticals Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The trial consists of two phases: phase Ia dose escalation and phase Ib dose optimization.For dose escalation part,an accelerated titration design (ATD) combined with "i3+3" design will be adopted.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Voluntarily participate and sign the informed consent form. 2. Age ≥ 18 years old, male or female. 3. Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1. 4. Expected survival ≥ 3 months. 5. Histologically or cytologically confirmed malignant solid tumors confirmed by histology and/or cytology, who have failed previous standard treatment (disease progression), are intolerant to standard treatment, or have no access to standard treatment. 6. At least one measurable lesion at baseline according to RECIST 1.1 criteria. 7. Adequate organ function. 8. Female subjects of childbearing potential or male subjects whose partners are of childbearing potential agree to use effective contraceptive measures. 9. Female subjects of childbearing potential must have a negative serum/urine pregnancy test within 7 days before the first dose. 10. Be able and willing to comply with the visits, treatment plans, laboratory tests, and other study-related procedures specified in the study protocol. 11. Adequate washout period of previous therapy before the first dose.
Exclusion criteria
1. Complicated with other malignant tumors within 3 years before the first dose. 2. History of brainstem, meningeal metastasis, spinal cord metastasis or compression, or carcinomatous meningitis; presence of active brain metastasis. 3. Screening imaging shows tumor invasion, compression, or occurrence in surrounding important organs or risk of esophagotracheal fistula or esophagopleural fistula. 4. Presence of clinically severe respiratory impairment caused by pulmonary disease complications. 5. Presence of the risk factors related to interstitial lung disease (ILD) or non-infectious pneumonia: 6. Presence of cardiovascular and cerebrovascular diseases or cardiovascular and cerebrovascular risk factors. 7. Uncontrolled infection. 8. Received live vaccines within 28 days before the first dose, or plan to receive live vaccines during the study period. 9. Toxicity of previous anti-tumor treatment has not fully or partially recovered. 10. Known allergy to any component of the study drug, or history of severe allergic reactions to other antibody drugs. 11. Pregnant and/or lactating women, or planning to become pregnant during the study period. 12. Known history of mental illness, substance abuse, alcoholism, etc., or other situations that the investigator deems may affect the safety or compliance of the study drug treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs), etc (Safety and tolerability of JSKN021) | From the first dose to 30 days after the last dose or until initiation of new anti-tumor treatment, whichever comes first. | Frequency and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs), etc.; abnormalities in physical examinations, laboratory tests, electrocardiograms, and other safety measures. |
| Dose-limiting toxicity (DLT) | 21 days from the first dose | Incidence of dose-limiting toxicity (DLT) in each dose group. |
| Optimal biological dose (OBD) and/or recommended Phase Ⅱ dose (RP2D) of JSKN021. | Up to 24 months | Based on safety and efficacy data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Up to 24months | 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） |
| Duration of response (DoR) | Up to 24months | Duration of response (DoR) assessed according to RECIST v1.1. |
| Disease control rate (DCR) | Up to 24months | Disease control rate (DCR) assessed according to RECIST v1.1. |
| Progression-Free Survival (PFS) | Up to 24months | Progression-free survival (PFS) is defined as the time from the date of initial administration till the first documentation of disease progression or death due to any cause (whichever occurs first). |
| Overall survival(OS) | Up to 24months | Overall Survival (OS) is defined as the time from the date of initial administration till death due to any cause. |
| Immunogenicity | Up to 24months | Incidence and titer changes of anti-drug antibodies (ADAs) and neutralizing antibodies (Nabs, if applicable) |
| Maximum concentration (Cmax) of JSKN021 | Up to 24months | Maximum concentration (Cmax) of JSKN021 |
| Time to maximum concentration (Tmax) of JSKN021 | Up to 24 months. | Time to maximum concentration (Tmax) of JSKN021 |
| Trough concentration (Ctrough) of JSKN021 | Up to 24 months | Trough concentration (Ctrough) of JSKN021 |
| Area under the concentration-time curve of JSKN021 | Up to 24 months | Area under the concentration-time curve of JSKN021 |
| Volume of distribution (V) of JSKN021 | Up to 24 months | Volume of distribution (V) of JSKN021 |
| Elimination half-life (t1/2) of JSKN021 | Up to 24 months | Elimination half-life (t1/2) of JSKN021 |
| Clearance (CL) of JSKN021 | Up to 24 months | Clearance (CL) of JSKN021 |
Countries
China
Contacts
CONTACTJian Zhang, MD
Outcome results
None listed