Study on the Efficacy and Safety of JSKN016 as Neoadjuvant Therapy in Resectable Stage II-III Non-small Cell Lung Cancer Patients

Study on the Efficacy and Safety of JSKN016 Combined With Toripalimab and Carboplatin as Neoadjuvant Therapy in Resectable Stage II-III Non-small Cell Lung Cancer Patients

This study aims to evaluate the efficacy and safety of JSKN016 combined with toripalimab and carboplatin as a neoadjuvant treatment regimen in patients with resectable stage II-III NSCLC.

Study Overview

• Status: Not yet recruiting
• Conditions: NSCLC Stage II
• Intervention / Treatment: Drug: JSKN016 + Toripalimab + Carboplatin

Detailed Description

Enrolled subjects were histologically confirmed resectable stage II, IIIA, and IIIB NSCLC (according to the 9th edition AJCC Lung Cancer TNM Staging System), with no evidence of distant metastasis and no evidence of unresectable local regional tumor extension.

• Study Type: Interventional
• Enrollment (Estimated): 54
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Junqi Wu, MD; Phone Number: 86-19102122052; Email: wujq0724@163.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200433
      • Shanghai Pulmonary Hospital
      • Contact: Chang Chen, MD, PhD; Phone Number: 2074 86-021-65115006; Email: chenthoracic@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• The subject is able to understand the informed consent form, voluntarily participate in the study, and has signed the informed consent form.
• The subject is ≥18 years and ≤80 years of age on the day of signing the informed consent form; both males and females are eligible.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically or cytologically confirmed resectable stage II, IIIA, or IIIB non-small cell lung cancer (NSCLC), according to the AJCC 9th edition TNM staging system for lung cancer.
• The subject has not previously received any anti-tumor therapy, including but not limited to systemic chemotherapy, immunotherapy, targeted therapy, or radiotherapy. Subjects who have received traditional Chinese medicine for anti-tumor indications are permitted to enroll provided a washout period of at least 2 weeks has elapsed.
• Tumor tissue genetic testing confirms NSCLC without EGFR sensitizing mutations (19del/L858R) and negative for ALK fusion genes.

Note: EGFR status may be determined using cytological or blood-based testing results. For subjects with squamous NSCLC, if EGFR and ALK status are previously unknown, testing is not required prior to enrollment in this study and will be considered negative.

• At least one measurable lesion at baseline according to RECIST version 1.1.

• Adequate organ function. The following laboratory test results must be obtained within 7 days prior to the first dose (echocardiography is permitted within 28 days prior to the first dose):

  1. Bone marrow function (no transfusion of whole blood or blood components within 14 days before the first dose; no hematopoietic growth factors within 7 days before the first dose):

     Absolute neutrophil count ≥ 1.5 × 10⁹/L Hemoglobin ≥ 90 g/L Platelet count ≥ 100 × 10⁹/L

  2. Liver function:

     Total bilirubin ≤ 1.5 × upper limit of normal (ULN) ALT and AST ≤ 3 × ULN

  3. Renal function:

     Serum creatinine ≤ 1.5 × ULN, or creatinine clearance (Ccr) ≥ 50 mL/min calculated using the Cockcroft-Gault formula (see Appendix 4)

  4. Coagulation function:

     International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN

  5. Cardiac function:

     Left ventricular ejection fraction (LVEF) ≥ 50% measured by echocardiography

  6. Pulmonary function:

Pulmonary function considered adequate for surgery as determined by the investigator.

• Female subjects of childbearing potential or male subjects whose partners are of childbearing potential must agree to use highly effective contraception from the time of signing the informed consent form until 24 weeks after the last dose. Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to the first dose.
• The subject is able and willing to comply with study protocol requirements, including study visits, treatment plans, laboratory tests, and other study-related procedures.

Exclusion Criteria:

• Histopathological evidence of any small cell carcinoma component, or diagnosis of large cell neuroendocrine carcinoma or sarcomatoid carcinoma.
• Presence of another malignancy within 3 years prior to the first dose, except for tumors that have been clinically cured by local treatment and have an extremely low risk of recurrence (e.g., cutaneous squamous cell carcinoma, basal cell carcinoma of the skin, non-muscle-invasive bladder cancer, carcinoma in situ of the cervix, localized prostate cancer, etc.), or tumors with disease-free survival ≥ 3 years after curative treatment and an extremely low risk of recurrence or metastasis (e.g., ductal carcinoma in situ after radical surgery, papillary thyroid carcinoma after radical surgery, etc.).

• Insufficient washout from prior treatments before the first dose, including:

  1. Use of any investigational drug within 28 days prior to the first dose;
  2. Use of traditional Chinese herbal medicine or proprietary Chinese medicine with clear anti-tumor indications within 14 days prior to the first dose;
  3. Receipt of non-specific immunomodulatory therapy (e.g., interleukin, interferon, thymosin, tumor necrosis factor, etc.) within 14 days prior to the first dose;

  4. Requirement for systemic glucocorticoids (>10 mg/day prednisone or equivalent doses of other glucocorticoids) for more than 7 consecutive days, or immunosuppressive therapy, within 14 days prior to the first dose.

     Exceptions include inhaled or topical corticosteroids, or physiologic replacement doses for adrenal insufficiency. Short-term (≤7 days) corticosteroid use is permitted for prophylaxis (e.g., prevention of contrast-agent allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity due to allergen exposure);

  5. Major surgery (e.g., abdominal or thoracic surgery) within 28 days prior to the first dose, excluding minor procedures such as diagnostic puncture, implantation of infusion devices, or biliary stent placement, or anticipated need for major surgery during the study period;
  6. Receipt of live vaccines within 28 days prior to the first dose, or planned administration of live vaccines during the study period.

• Presence of interstitial lung disease (ILD) or risk factors related to non-infectious pneumonitis, including:

  1. History or current presence of ILD or non-infectious pneumonitis requiring systemic glucocorticoids or other immunosuppressive therapy;
  2. Suspected ILD or non-infectious pneumonitis that cannot be excluded by imaging during the screening period.
• Presence of active autoimmune disease requiring systemic treatment within the past 2 years (e.g., treatment with disease-modifying agents, corticosteroids, or immunosuppressive drugs).

Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment.

• Uncontrolled infections, including but not limited to:

  1. Active HBV or HCV infection. Patients positive for HBsAg must undergo HBV-DNA testing; if HBV-DNA exceeds the lower limit of detection of the local laboratory, enrollment is permitted provided antiviral therapy is administered.

     Patients positive for HCV-Ab may be enrolled if HCV-RNA is negative;

  2. Severe infection within 4 weeks prior to the first dose, including but not limited to infections with complications requiring hospitalization, sepsis, or severe pneumonia; or active infection requiring systemic anti-infective therapy within 2 weeks prior to the first dose;
  3. History of immunodeficiency, positive HIV test, or history of acquired immunodeficiency syndrome (AIDS);
  4. Known active tuberculosis;
  5. Active syphilis.
• History of allogeneic bone marrow transplantation or organ transplantation.
• Known hypersensitivity to any component of the investigational drug, or a history of severe allergic reactions to other antibody-based therapies.
• Pregnant or breastfeeding women, or women planning to become pregnant during the study period.
• Known psychiatric disorders, substance abuse, alcohol abuse, or any other condition that, in the investigator's judgment, may affect the safety of study treatment or subject compliance.
• Any other disease, treatment, or laboratory abnormality, either past or present, that in the investigator's judgment may interfere with the evaluation of safety or efficacy, prevent full participation in the study, or make participation not in the subject's best interest.

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: JSKN016+Toripalimab+Carboplatin

Drug: JSKN016 + Toripalimab + Carboplatin; During the neoadjuvant treatment phase, enrolled subjects will receive combination therapy with JSKN016 (4 mg/kg) + toripalimab (240 mg) + carboplatin (AUC 5) in 3-week cycles, with a maximum of 4 cycles. Subjects meeting surgical criteria will undergo surgery within 8 weeks after the last neoadjuvant treatment cycle. A preoperative visit will be conducted 1 week (±1 week) prior to surgery. Surgery may be advanced if the investigator determines the subject is stable and fit for surgery, provided it occurs at least 7 days after the last study drug administration. Resected tumor specimens will undergo assessment of surgical margins and extent of resection (R0, R1/R2). Tumor tissue will be evaluated for pathological response (MPR and pCR). Subsequent adjuvant therapy will follow standard clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response (PCR) Rate	PCR is defined as the absence of any viable tumor cells in the primary tumor site and all sampled lymph node regions of the resected specimen after neoadjuvant therapy, as confirmed by complete pathological assessment.	About 5 months after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)		Up to 4 years
Major Pathological Response (MPR) Rate	MPR is defined as the proportion of viable tumor cells in the resected primary tumor site after neoadjuvant therapy being ≤ 10%.	about 5 months after enrollment
Event-Free Survival (EFS)		up to 4 years
Disease Control Rate(DCR)	Disease Control Rate (DCR) refers to the proportion of patients whose tumors or diseases achieve "Complete Response (CR)," "Partial Response (PR)," or "Stable Disease (SD)" (according to RECIST1.1) after receiving drug treatment	About 4-5 months after enrollment
Surgery Completion Rate	The proportion of subjects who underwent lung cancer resection among those receiving the therapy.	Up to 8 weeks after administration of the final neoadjuvant therapy dose
R0 Resection Rate	The proportion of subjects who underwent lung cancer resection and achieved complete resection (R0) among those receiving the therapy.	About 5 months after enrollment
Safety and Tolerability	Number of participants with treatment-related adverse events (AEs) and serious adverse events (SAEs) as assessed by CTCAE v6.0.	From the subject's written consent to participate in the study through 30 days after the final administration of the drug

Collaborators and Investigators

• Sponsor: Shanghai Pulmonary Hospital, Shanghai, China
• Investigators: Principal Investigator: Chang Chen, MD, PhD, Shanghai Pulmonary Hospital, Shanghai, China

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: March 4, 2026
• First Submitted That Met QC Criteria: March 20, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: March 1, 2026

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; Organic Chemicals; Coordination Complexes; Carboplatin; toripalimab
• Other Study ID Numbers: STAR-019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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