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

Official title

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

Overview

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.

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.

Interventions

• Drug IBI363 + Chemotherapy
  1. Neoadjuvant treatment: IBI363 combined with platinum-based chemotherapy. 2. 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.

Primary outcome measures

• R0 Rate [Time frame: about 4 months after enrollment]

Secondary outcome measures (7)

• MPR Rate [Time frame: about 5 months after enrollment]
• pCR Rate [Time frame: about 5 months after enrollment]
• Tumor Downstaging Rate [Time frame: up to 4 months]
• Overall Response Rate (ORR) [Time frame: 12 weeks]
• 2-Year EFS Rate [Time frame: up to 2 years]
• 2-Year OS Rate [Time frame: up to 2 years]
• Incidence of Treatment-related Adverse Events [Time frame: From the subject's written consent to participate in the study through 30 days after the final administration of the drug]

Eligibility criteria

Inclusion criteria

• The patient shall sign the informed consent.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Histologically or cytologically confirmed Stage III (per AJCC 9th) squamous or non-squamous non-small-cell lung cancer (NSCLC) deemed unresectable by the investigator.
• 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.
• "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.
• At least one measurable lesion per RECIST v1.1.
• 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 %
• Contraception and reproductive status:
• 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

• Non-squamous and squamous NSCLC with EGFR active mutation positive, ALK rearrangement, or any other driver mutation with an approved targeted therapy.
• 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.
• Histologically confirmed the presence of small cell lung cancer component.
• Participants who have received any systemic anti-cancer treatment.
• Clinically significant cardiovascular or cerebrovascular disease, including:

• Myocardial infarction or unstable angina within 6 months before first dose
• Stroke or transient ischaemic attack within 6 months before first dose
• Uncontrolled hypertension (systolic ≥ 160 mmHg and/or diastolic ≥ 100 mmHg) despite optimal therapy
• Congestive heart failure (NYHA class III-IV)
• Myocarditis
• 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.
• Presence of any active autoimmune disease or history of autoimmune disease.
• Idiopathic pulmonary fibrosis, organizing pneumonia, drug pneumonia, or active pneumonia shown on CT during screening period have been or are currently present.
• History of allogeneic haematopoietic stem-cell or solid-organ transplantation.
• The subject has congenital or acquired immune deficiency (such as HIV infected persons).
• 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.)
• Participants who are allergic to the test drug or any auxiliary materials.
• The vaccine was administered within 30 days before first dose or planned during treatment and up to 90 days after the last dose.
• Severe active infection within 2 weeks before first dose.
• Other factors that may increase study risk, interfere with results, or render the patient unsuitable per investigator judgment.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shanghai Pulmonary Hospital — Shanghai

Identifiers

NCT: NCT07408635 · STAR-017

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗