Evaluation of JSKN016 Combination Therapy in Subjects with NSCLC

Phase 1

Not yet recruiting

• Conditions: Advanced Non-small Cell Lung Cancer
• Interventions: Drug: JSKN016; Drug: Carboplatin; Drug: Furmonertinib Mesylate; Drug: Ivonescimab; Drug: Docetaxel; Drug: Tislelizumab; Drug: Pembrolizumab

• Registration Number: NCT06868732
• Lead Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd

Brief Summary

This is a Phase Ib clinical study conducted in China to evaluate the treatment of advanced non-small cell lung cancer with JSKN016 in combination therapy. The enrolled subjects are all in the locally advanced or metastatic stage of non-small cell lung cancer.

Detailed Description

This is a Phase Ib clinical study conducted in China to evaluate the treatment of advanced non-small cell lung cancer with JSKN016 in combination therapy. The enrolled subjects are all in the locally advanced or metastatic stage of non-small cell lung cancer. The primary objective of the study is to assess the efficacy and safety of JSKN016 in combination therapy in selected subjects with advanced non-small cell lung cancer.

Study Timeline

• Status Verified: 2025-03
• Study First Submitted: 2025-03-05
• Study First Submitted QC: 2025-03-09
• Last Update Submitted: 2025-03-09
• Study First Posted: 2025-03-11
• Last Update Posted: 2025-03-11
• Study Start: 2025-03-12
• Primary Completion: 2028-06-30
• Study Completion: 2028-12-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 288

Inclusion Criteria

1. Voluntarily participate and sign the informed consent form.
2. Age ≥ 18 years old, ≤ 75 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.
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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort -1A-a	JSKN016	Receive JSKN016 in combination with carboplatin, administered intravenously at the dosage specified in the protocol.
Cohort -1A-a	Carboplatin	Receive JSKN016 in combination with carboplatin, administered intravenously at the dosage specified in the protocol.
Cohort -1A-b	JSKN016	Receive JSKN016 in combination with furmonertinib mesilate tablets, administered at the dosage specified in the protocol.
Cohort -1A-b	Furmonertinib Mesylate	Receive JSKN016 in combination with furmonertinib mesilate tablets, administered at the dosage specified in the protocol.
Cohort -1B-c	JSKN016	Receive JSKN016 in combination with ivonescimab, administered intravenously at the dosage specified in the protocol.
Cohort -1B-c	Ivonescimab	Receive JSKN016 in combination with ivonescimab, administered intravenously at the dosage specified in the protocol.
Cohort -1B-d	JSKN016	Receive JSKN016 in combination with ivonescimab and carboplatin, administered intravenously at the dosage specified in the protocol.
Cohort -1B-d	Carboplatin	Receive JSKN016 in combination with ivonescimab and carboplatin, administered intravenously at the dosage specified in the protocol.
Cohort -1B-d	Ivonescimab	Receive JSKN016 in combination with ivonescimab and carboplatin, administered intravenously at the dosage specified in the protocol.
Cohort -2	JSKN016	Receive JSKN016 in combination with docetaxel, administered intravenously at the dosage specified in the protocol.
Cohort -2	Docetaxel	Receive JSKN016 in combination with docetaxel, administered intravenously at the dosage specified in the protocol.
Cohort -3-f	JSKN016	Receive JSKN016 in combination with tislelizumab, administered intravenously at the dosage specified in the protocol.
Cohort -3-f	Tislelizumab	Receive JSKN016 in combination with tislelizumab, administered intravenously at the dosage specified in the protocol.
Cohort -3-g	JSKN016	Receive JSKN016 in combination with tislelizumab and carboplatin, administered intravenously at the dosage specified in the protocol.
Cohort -3-g	Carboplatin	Receive JSKN016 in combination with tislelizumab and carboplatin, administered intravenously at the dosage specified in the protocol.
Cohort -3-g	Tislelizumab	Receive JSKN016 in combination with tislelizumab and carboplatin, administered intravenously at the dosage specified in the protocol.
Cohort -4	JSKN016	Receive JSKN016 in combination with pembrolizumab, administered intravenously at the dosage specified in the protocol.
Cohort -4	Pembrolizumab	Receive JSKN016 in combination with pembrolizumab, administered intravenously at the dosage specified in the protocol.

Primary Outcome Measures

Name	Time	Method
ORR assessed by the investigator per RECIST v1.1	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)
Safety reflected by AE	Up to 24months	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.

Secondary Outcome Measures

Name	Time	Method
DOR assessed by the investigator per RECIST v1.1	Up to 24months	Duration of response (DoR) assessed according to RECIST v1.1.
DCR assessed by the investigator per RECIST v1.1	Up to 24months	Disease control rate (DCR) assessed according to RECIST v1.1.
TTR assessed by the investigator per RECIST v1.1	Up to 24months	Time to response (TTR) is defined as the time to response base on RECIST v1.1.
PFS assessed by investigator per RECIST v1.1	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 assessed by the investigator or death due to any cause (whichever occurs first).
OS	Up to 24months	Overall Survival (OS) is defined as the time from the date of initial administration till death due to any cause.
Peak Plasma Concentration (Cmax)	Up to 24months	The Peak Plasma Concentration (Cmax) of the antibody-drug conjugate (ADC), total antibody and free payload.
Trough Plasma Concentration (Cmin)	Up to 24 months	The Trough Plasma Concentration (Cmin) of the antibody-drug conjugate (ADC), total antibody and free payload.
ADA	Up to 24months	Number of subjects with detectable anti-drug antibodies (ADA).