A Phase II Clinical Study to Evaluate the Safety, Efficacy, Pharmacokinetics/Pharmacodynamics of JSKN033 in Patients With Advanced Non-Small Cell Lung Cancer

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Non Small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: JSKN033 Injection

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lin Wu, Doctor; Phone Number: +86 731 8976 2300; Email: wulin-calf@vip.163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 (Dose Selection) and Part 2 (Cohort Expansion); JSKN033 is administered at the predefined dose, once per treatment cycle.	Drug: JSKN033 Injection; JSKN033 is a fixed-dose combination consisting of JSKN003 (a HER2-targeted ADC) and envafolimab (a PD-L1 inhibitor)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and Severity of Treatment-emergent Adverse Events (TEAEs)	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.	Baseline up to 30 days after the last dose of study drug, up to 1 year
Objective response rate (ORR)	ORR was defined as the proportion of subjects achieving Complete Response (CR) or Partial Response (PR)	Up to 1 year after the last participant receives the last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DoR)	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	Up to 1 year after the last participant receives the last dose
Disease control rate (DCR)	DCR was defined as the proportion of subjects whose best overall response is CR, PR, or Stable Disease (SD)	Up to 1 year after the last participant receives the last dose
Clinical benefit rate (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.	Up to 1 year after the last participant receives the last dose
Progression-free Survival (PFS)	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".	Up to 1 year after the last participant receives the last dose
Overall survival (OS)	OS was defined as the time from the date of first dose until the date of death from any cause	Up to 1 year after the last participant receives the last dose
PK parameter: Cmax	Maximum (Peak) Observed blood Concentration (Cmax)	Post last dose up to Day 90
PK parameter: Tmax	Time of Maximum blood Concentration (Tmax)	Post last dose up to Day 90
PK parameter: AUC	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.	Post last dose up to Day 90
PK parameter: Terminal Elimination Half-life (t1/2)		Post last dose up to Day 90
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

Other Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd

Study record dates

Study Major Dates

• Study Start (Estimated): December 10, 2025
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): August 30, 2027

Study Registration Dates

• First Submitted: December 2, 2025
• First Submitted That Met QC Criteria: December 2, 2025
• First Posted (Actual): December 15, 2025

Study Record Updates

• Last Update Posted (Actual): December 15, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: JSKN033-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No