Evaluation of JSKN016 in the Treatment of Advanced Non-small Cell Lung Cance： a Phase II Clinical Study

This is a Phase II clinical study conducted in China to evaluate the treatment of advanced non-small cell lung cancer with JSKN016. The enrolled subjects are all in the locally advanced or metastatic stage of non-small cell lung cancer.The study is divided into two parts. The main objective of part I is to assess the efficacy and safety of JSKN016 in selected subjects with advanced non-small cell lung cancer. The main objective of part II is to compare the efficacy of JSKN016 and docetaxel in subjects with advanced non-small cell lung cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: JSKN016; Drug: Docetaxel

Detailed Description

This is a Phase II clinical study conducted in China to evaluate the treatment of advanced non-small cell lung cancer with JSKN016. The enrolled subjects are all in the locally advanced or metastatic stage of non-small cell lung cancer.The study is divided into two parts. The main objective of part I is to assess the efficacy and safety of JSKN016 in selected subjects with advanced non-small cell lung cancer. The main objective of part II is to compare the efficacy of JSKN016 and docetaxel in subjects with advanced non-small cell lung cancer.

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Li Zhang; Phone Number: 13902282893; Email: zhangli@sysucc.org.cn

Participation Criteria

Eligibility Criteria

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

Description

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 locally advanced or metastatic non-small cell lung cancer (NSCLC) that is not suitable for radical surgery and/or radical radiotherapy, and meets one of the following conditions: EGFR sensitive mutations, and failed treatment with EGFR-TKI; Driver gene negative, treated with PD-1/L1 inhibitors and a platinum-containing chemotherapy and treatment failure; Positive driver gene, failure of corresponding standard therapy;
6. At least one extracranial measurable lesion at baseline according to RECIST 1.1 criteria.
7. Recently archived or fresh tumor tissue samples are available.
8. Have good organ function.
9. Have no current birth plans and agree to contraception during the trial.

Exclusion Criteria:

1. Presence of any small cell carcinoma component in histopathology.
2. Subjects with other malignant tumors within 5 years prior to enrollment, and other tumors have been cured through local therapy, such as cured cutaneous squamous cell carcinoma, basal cell carcinoma, non-primary invasive bladder cancer, and prostate/cervical/breast cancer in situ.
3. Presence of brainstem, meningeal metastases, spinal cord metastases or compression, leptomeningeal metastases, or history of carcinomatous meningitis; Presence of active brain metastases.
4. During the screening period, imaging shows that the tumor invades, compresses, or occurs in the surrounding important organs (such as the heart and pericardium, trachea, esophagus, superior vena cava, etc.) or there is a risk of esophageal tracheal fistula or esophageal pleural fistula.
5. Adequate washout of previous therapy before the first dose.
6. Gastrointestinal abnormalities with obvious clinical manifestations.
7. Presence of clinically severe respiratory impairment caused by pulmonary disease complications.
8. Presence of cardiovascular and cerebrovascular diseases or cardiovascular and cerebrovascular risk factors.
9. Prior treatment with topoisomerase I inhibitors (e.g., irinotecan, topotecan), antibody-drug conjugates containing topoisomerase I inhibitors (e.g., DS-8201, HER3-DXd, DS-1062), or targeting TROP2 or HER3.
10. Previous treatment with docetaxel.
11. Have an uncontrolled infection, a history of immunodeficiency, a positive human immunodeficiency virus (HIV) test, or a history of AIDS.
12. Previous history of allogeneic bone marrow or organ transplantation.
13. Known allergy to any component of the study drug, and previous history of severe allergic reaction to other antibody drugs.
14. Pregnant and/or lactating females.
15. Have local or systemic diseases caused by non-malignant tumors, or diseases or symptoms secondary to tumors, which can lead to higher medical risk and/or uncertainty in survival evaluation, such as tumor leukemia response , cachexia manifestations, etc.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part I: Cohort 1（JSKN016）; Enrolled subjects with harboring sensitive EGFR mutations who have already received tyrosine kinase inhibitor (TKI) therapy.Receive JSKN016 monotherapy , administered intravenously at the dosage specified in the protocol.	Drug: JSKN016; Administered intravenously according to protocol.
Experimental: Part I: Cohort 2（JSKN016）; Enrolled subjects with negative driver genes who have already received immunotherapy. Receive JSKN016 monotherapy , administered intravenously at the dosage specified in the protocol.	Drug: JSKN016; Administered intravenously according to protocol.
Experimental: Part I: Cohort 3（JSKN016）; Enrolled subjects with positive driver genes who have failed standard therapy.Receive JSKN016 monotherapy , administered intravenously at the dosage specified in the protocol.	Drug: JSKN016; Administered intravenously according to protocol.
Experimental: Part II：Cohort A（JSKN016）; Receive JSKN016 monotherapy , administered intravenously at the dosage specified in the protocol.	Drug: JSKN016; Administered intravenously according to protocol.
Active Comparator: Part II：Cohort B（Docetaxel）; Receive Docetaxel monotherapy , administered intravenously at the dosage specified in the protocol.	Drug: Docetaxel; Administered intravenously according to protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR assessed by the investigator per RECIST v1.1	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）	Up to 24months
Safety reflected by AE	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.	Up to 24months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DOR assessed by the investigator per RECIST v1.1	Duration of response (DoR) assessed according to RECIST v1.1.	Up to 24months
DCR assessed by the investigator per RECIST v1.1	Disease control rate (DCR) assessed according to RECIST v1.1.	Up to 24months
TTR assessed by the investigator per RECIST v1.1	Time to response (TTR) is defined as the time to response base on RECIST v1.1.	Up to 24months
PFS assessed by investigator per RECIST v1.1	Progression-free survival (PFS) is defined as the time from the date of initial administration till the first documentation of disease progression assessed by the investigator or death due to any cause (whichever occurs first).	Up to 24months
OS	Overall Survival (OS) is defined as the time from the date of initial administration till death due to any cause.	Up to 24months
Cmax of JSKN016	Maximum (Peak) Observed blood Concentration (Cmax) of JSKN016 Following First Dose	Up to 24months
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.	Up to 24months
Tmax of JSKN016	Time of Maximum blood Concentration (Tmax) of JSKN016 Following First Dose	Up to 24months
ADA	Number of subjects with detectable anti-drug antibodies (ADA).	Up to 24months

Collaborators and Investigators

• Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd
• Investigators: Principal Investigator: Li Zhang, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): January 17, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: December 30, 2024
• First Submitted That Met QC Criteria: January 13, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 13, 2025
• Last Verified: January 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; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: JSKN016-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No