IBI363 (PD-1/IL-2α-bias) in Combination With Chemotherapy as Neoadjuvant Therapy in Initially Unresectable Stage III Non-Small Cell Lung Cancer

IBI363 (PD-1/IL-2α-bias) in Combination With Chemotherapy as Neoadjuvant Therapy to Convert Initially Unresectable Stage III Non-Small Cell Lung Cancer To Resectable Disease: a Phase II, Single-Arm Clinical Trial

This study is a single-arm, phase II clinical trial evaluating the safety and efficacy of IBI363 combined with chemotherapy as a neoadjuvant treatment of non-small cell lung cancer.

Study Overview

• Status: Recruiting
• Conditions: Unresectable Stage III Non-small Cell Lung Cancer; Carcinoma, Non-Small-Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: IBI363 + Chemotherapy

Detailed Description

NSCLC patients receive IBI363 combined with platinum-based chemotherapy. If multidisciplinary team (MDT) assessment determines the patient is surgically eligible, surgery is performed followed by 1 year of standard adjuvant therapy. If, after 4 treatment cycles, MDT assessment determines the tumor remains unresectable, concurrent chemoradiotherapy followed by immune checkpoint inhibitor consolidation therapy is administered. This study aims to evaluate the efficacy of IBI363 combined with chemotherapy for neoadjuvant treatment of initially unresectable NSCLC based on R0 resection rate, major pathological response (MPR) rate, and pathological complete response (pCR) rate.

• Study Type: Interventional
• Enrollment (Estimated): 43
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chang Chen, MD; Phone Number: +86 21 65115006; Email: changchenc@hotmail.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Shanghai Pulmonary Hospital
    • Contact: Chang Chen, MD; Phone Number: +86 21 65115006; Email: changchenc@hotmail.com

Participation Criteria

Eligibility Criteria

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

Description

INCLUSION CRITERIA

1. The patient shall sign the informed consent.
2. Age ≥ 18 years.
3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
4. Histologically or cytologically confirmed Stage III (per AJCC 9th) squamous or non-squamous non-small-cell lung cancer (NSCLC) deemed unresectable by the investigator.
5. Tumours with mixed NSCLC histology must be categorised as either squamous or non-squamous on the basis of the predominant component. Tumours containing both NSCLC and small-cell lung cancer (SCLC) are excluded.
6. "Unresectable" is defined as following: (1) Multistation or confluent metastasis in ipsilateral mediastinal lymph nodes (2)Contralateral or supraclavicular lymph node metastasis (N3) (3)Invasion of critical organs or major blood vessels (4)Extensive invasion of the chest wall and pleura (5)Special anatomical locations (6）Patient intolerance to lobectomy or pneumonectomy.
7. At least one measurable lesion per RECIST v1.1.

8. Adequate organ function meet the following standards (within 14 days before first dose, any blood components or growth factor drugs is not permitted):

   • ANC count ≥ 1.5 × 10⁹/L
   • Platelet count ≥ 100 × 10⁹/L
   • Hemoglobin ≥ 90 g/L
   • Serum Cr ≤ 1.5 times of upper limit of normal (ULN) or calculated creatinine clearance (CLcr) ≥ 50 mL/min
   • Total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN in Gilbert's syndrome)
   • AST and ALT ≤ 2.5 × ULN
   • INR or APPT ≤ 1.5 × ULN
   • left ventricular ejection fraction (LVEF) ≥ 50 %
9. Contraception and reproductive status:
10. Fertile female patients must voluntarily use effective contraception during the study period and for at least 3 months after treatment completion, and urine or serum pregnancy test result within 72 hours prior to enrollment are negative and must not be breastfeeding. Male patients with female partners of childbearing potential must use effective contraception during the trial and for 3 months after the last dose of IBI363.

EXCLUSION CRITERIA

1. Non-squamous and squamous NSCLC with EGFR active mutation positive, ALK rearrangement, or any other driver mutation with an approved targeted therapy.
2. History of other malignant tumors within five years or concurrently present, except adequately treated cervical carcinoma in situ, basal- or squamous-cell skin carcinoma, localized prostate cancer after radical prostatectomy, ductal carcinoma in situ after radical prostatectomy, or other tumor deemed cured by the investigator.
3. Histologically confirmed the presence of small cell lung cancer component.
4. Participants who have received any systemic anti-cancer treatment.

5. Clinically significant cardiovascular or cerebrovascular disease, including:

   1. Myocardial infarction or unstable angina within 6 months before first dose
   2. Stroke or transient ischaemic attack within 6 months before first dose
   3. Uncontrolled hypertension (systolic ≥ 160 mmHg and/or diastolic ≥ 100 mmHg) despite optimal therapy
   4. Congestive heart failure (NYHA class III-IV)
   5. Myocarditis
6. Participants who were systemically treated with corticosteroids (prednisone or other corticosteroids >10 mg/ day) or other immunosuppressive agents within 2 weeks prior to first administration. In the absence of active autoimmune disease, inhaled or topical corticosteroids and adrenal hormone replacement therapy are permitted.
7. Presence of any active autoimmune disease or history of autoimmune disease.
8. Idiopathic pulmonary fibrosis, organizing pneumonia, drug pneumonia, or active pneumonia shown on CT during screening period have been or are currently present.
9. History of allogeneic haematopoietic stem-cell or solid-organ transplantation.
10. The subject has congenital or acquired immune deficiency (such as HIV infected persons).
11. Active hepatitis (HBsAg positive and HBV DNA >the upper limit of normal value; HCV antibody and HCV RNA positive. Subjects who meet the following criteria may be enrolled: HBV-DNA <500 IU/mL measured within 28 days prior to study dosing, have received at least 4 weeks of standard antiviral therapy, and are willing to continue antiviral therapy throughout the study period.)
12. Participants who are allergic to the test drug or any auxiliary materials.
13. The vaccine was administered within 30 days before first dose or planned during treatment and up to 90 days after the last dose.
14. Severe active infection within 2 weeks before first dose.
15. Other factors that may increase study risk, interfere with results, or render the patient unsuitable per investigator judgment.

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: IBI363 + Chemotherapy; Neoadjuvant therapy phase:IBI363 combined with platinum-based chemotherapy.; Surgery phase: Participants deemed operable by the MDT will undergo surgery, and then can continue to receive standard adjuvant therapy for one year. If the NSCLC remained unresectable, concurrent chemoradiotherapy was administered followed by immune checkpoint inhibitor consolidation therapy to maintain.

Drug: IBI363 + Chemotherapy; Neoadjuvant treatment:IBI363 combined with platinum-based chemotherapy.; Multidisciplinary team(MDT) assessment: Participants deemed operable by the MDT will undergo surgery, and then can continue to receive standard adjuvant therapy for one year. If the NSCLC remained unresectable, concurrent chemoradiotherapy was administered followed by immune checkpoint inhibitor consolidation therapy to maintain.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 Rate	The proportion of subjects who underwent lung cancer resection and achieved complete resection (R0) among those receiving IBI363 combined chemotherapy conversion therapy.	about 4 months after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MPR Rate	Defined as the proportion of patients who have achieved major pathologic response (with ≤10% viable tumor cells) in all patients after surgery.	about 5 months after enrollment
Overall Response Rate (ORR)	The proportion of patients who have had a complete response (CR) or partial response (PR) (according to RECIST1.1) after the neoadjuvant therapy.	12 weeks
pCR Rate	Defined as the proportion of all patients who completed treatment and had no invasive viable tumor in both the primary tumor (lung) and the sampled lymph nodes after surgery	about 5 months after enrollment
Tumor Downstaging Rate	Defined as the proportion of patients whose imaging stage is downgraded through conversion therapy.	up to 4 months
2-Year EFS Rate	The 2-year EFS rate is estimated using Kaplan-Meier survival analysis. The time from randomization to first occurrence of progression, disease recurrence (including local and distant recurrence), or death from any cause is assessed according to RECIST v1.1.	up to 2 years
2-Year OS Rate	The 2-year OS rate is estimated based on the Kaplan-Meier survival analysis. OS is defined as the time from enrollment to death due to any cause.	up to 2 years
Incidence of Treatment-related Adverse Events	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

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2026
• Primary Completion (Estimated): June 6, 2028
• Study Completion (Estimated): January 6, 2030

Study Registration Dates

• First Submitted: January 22, 2026
• First Submitted That Met QC Criteria: February 12, 2026
• First Posted (Actual): February 13, 2026

Study Record Updates

• Last Update Posted (Actual): February 13, 2026
• Last Update Submitted That Met QC Criteria: February 12, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma; Carcinoma, Non-Small-Cell Lung; Therapeutics; Drug Therapy
• Other Study ID Numbers: STAR-017

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