Non Small Cell Lung Cancer (NSCLC)
Conditions
Brief summary
This is an open-label, multicenter, Phase II clinical study designed to evaluate the safety and efficacy of JSKN033 in the treatment of patients with advanced NSCLC. The study is divided into two phases: Part 1 (Dose Selection) and Part 2 (Cohort Expansion). Enrolled subjects are patients with locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) NSCLC who are not eligible for curative treatment. Part 1 (Dose Selection): It consists of two dose groups, with a maximum of 20 subjects enrolled in each group. Part 2 (Cohort Expansion): It consists of two cohorts, with a maximum of 60 subjects enrolled in each cohort.
Interventions
JSKN033 is a fixed-dose combination consisting of JSKN003 (a HER2-targeted ADC) and envafolimab (a PD-L1 inhibitor)
Sponsors
Jiangsu Alphamab Biopharmaceuticals Co., Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects can understand the informed consent form,voluntarily participate in the study, and sign the informed consent form. 2. Subjects are≥18 years old on the day of signing the informed consent form, regardless of gender. 3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. 4. Expected survival time ≥3 months. 5. Histologically or cytologically confirmed locally advanced or metastatic NSCLC (per AJCC 8th Edition Lung Cancer TNM Staging) that is not eligible for curative surgery and/or curative radiotherapy. 6. NSCLC confirmed to be no other known driver gene alterations for which first- line targeted therapy has been approved. 7. For Part 1(Dose Selection): Enrolled subjects are those with advanced unresectable or metastatic NSCLC who have failed or are intolerant to standard previous treatments, and have HER2 mutation or HER2 expression in tumor tissue. 8. For Part 2 (Cohort Expansion): Enrolled subjects are those with locally advanced or metastatic NSCLC who have not received prior systemic anti-tumor treatment for their advanced disease. 9. Per RECIST 1.1 criteria,subjects have at least one extracranial measurable lesion at baseline. 10. Subjects must provide tumor tissue samples. 11. Sufficient organ function. 12. Female subjects of childbearing potential or male subjects whose partners are of childbearing potential agree to use highly effective contraceptive measures from the time of signing the informed consent form until 24 weeks after the last dose.
Exclusion criteria
1. Presence of any small cell carcinoma component in the histological pathology. 2. History of other malignant tumors within 5 years prior to the first dose administration. 3. History of brainstem, meningeal, or spinal cord metastases/compression, or carcinomatous meningitis; presence of active brain metastases. 4. Imaging during the screening phase shows tumor invasion, compression, or location in surrounding vital organs. 5. Sufficient washout period from previous treatments prior to the first dose. 6. Presence of the following lung diseases or medical history leading to severe respiratory impairment. 7. Presence of risk factors related to interstitial lung disease (ILD) or non-infectious pneumonia. 8. Presence of cardiovascular and cerebrovascular diseases or risk factors. 9. Presence of uncontrolled infections. 10. Toxicity from previous anti-tumor treatment has not recovered to grade≤1 (per CTCAE v5.0). 11. Previous history of allogeneic bone marrow or organ transplantation. 12. Known allergy to any component of the study drug. 13. Pregnant and/or lactating women, or women planning to become pregnant during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Up to 1 year after the last participant receives the last dose | ORR was defined as the proportion of subjects achieving Complete Response (CR) or Partial Response (PR) |
| Number and Severity of Treatment-emergent Adverse Events (TEAEs) | Baseline up to 30 days after the last dose of study drug, up to 1 year | The incidence and severity of TEAEs and TRAEs (Treatment-related Adverse Events, graded according to NCI CTCAE 5.0), Serious AEs (SAEs), laboratory tests, etc. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate (DCR) | Up to 1 year after the last participant receives the last dose | DCR was defined as the proportion of subjects whose best overall response is CR, PR, or Stable Disease (SD) |
| Clinical benefit rate (CBR) | Up to 1 year after the last participant receives the last dose | 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. |
| Progression-free Survival (PFS) | Up to 1 year after the last participant receives the last dose | PFS is defined as the time from the date of first study dose to disease progression or death whichever occurs first. Subjects without event (no disease progression or alive at last visit) will be censored at the date of last tumor assessment. |
| Overall survival (OS) | Up to 1 year after the last participant receives the last dose | OS was defined as the time from the date of first dose until the date of death from any cause |
| PK parameter: Cmax | Post last dose up to Day 90 | Maximum (Peak) Observed blood Concentration (Cmax) |
| PK parameter: Tmax | Post last dose up to Day 90 | Time of Maximum blood Concentration (Tmax) |
| PK parameter: AUC | Post last dose up to Day 90 | The blood PK parameters of JSKN033 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. |
| PK parameter: Volume of distribution (V) | Post last dose up to Day 90 | — |
| PK parameter: trough concentration (Ctrough) | Post last dose up to Day 90 | — |
| PK parameter: Clearance (CL) | Post last dose up to Day 90 | — |
| PK parameter: Accumulation index (Rac) | Post last dose up to Day 90 | — |
| PK parameter: Mean residence time (MRT) | Post last dose up to Day 90 | — |
| Incidence of anti-drug antibodies (ADAs), antibody titers, and incidence of neutralizing antibodies | Post last dose up to Day 90 | — |
| PK parameter: Terminal Elimination Half-life (t1/2) | Post last dose up to Day 90 | — |
| Duration of response (DoR) | Up to 1 year after the last participant receives the last dose | Duration of response for responders (CR or PR) is defined as the time interval between the date of earliest qualifying response and the date of PD or death for any cause, whichever occurs earlier |
Other
| Measure | Time frame |
|---|---|
| Correlation between biomarkers (HER2 mutation status, HER2/PD-L1 expression levels) in tumor tissue samples and efficacy. | Up to 1 year after the last participant receives the last dose |
Contacts
Primary ContactLin Wu, Doctor
Outcome results
None listed