Adebrelimab or Retlirafusp Alfa Plus Recaticimab and Chemotherapy for Resectable NSCLC

A Phase II Study of Neoadjuvant Adebrelimab or Retlirafusp Alfa (SHR-1701) in Combination With Recaticimab and Chemotherapy for Resectable Non-small Cell Lung Cancer

Although phase III studies have confirmed the efficacy and safety of perioperative immunotherapy plus chemotherapy for resectable NSCLC, there remains room for improvement in both short-term efficacy and long-term survival. Preclinical evidence suggests that PCSK-9 inhibition may synergize with PD-1 inhibitors to suppress tumor growth in mouse models. To date, no data are available on neoadjuvant PCSK-9 inhibitor therapy combined with immunotherapy and chemotherapy in resectable NSCLC. Therefore, this phase II study aims to evaluate the efficacy and safety of neoadjuvant adebrelimab or retlirafusp alfa (SHR-1701) plus recaticimab and chemotherapy in patients with resectable NSCLC.

Study Overview

• Status: Not yet recruiting
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Adebrelimab, Retlirafusp alfa, Recaticimab and chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 18-75 years old
• Histologically or cytologically confirmed resectable stage II, IIIA, or selected IIIB (T2-3N2bM0 only) non-small cell lung cancer (NSCLC) according to the International Union Against Cancer (UICC) and American Joint Committee on Cancer (AJCC) 9th edition TNM classification for lung cancer, with the tumor judged by the investigator as amenable to curative-intent R0 resection.
• Ability to provide tumor tissue specimens, either archived or freshly obtained prior to the first dose of study drug.
• Presence of measurable target lesions by computed tomography (CT) or magnetic resonance imaging (MRI) according to RECIST version 1.1. Tumor imaging assessment must be performed within 28 days before the first dose.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• No prior anti-cancer therapy, including radiotherapy, chemotherapy, surgery, or targeted therapy, before study enrollment.
• Adequate hematologic and end-organ function.

Exclusion Criteria:

• Histologically or cytologically confirmed small cell lung cancer (SCLC), mixed SCLC and NSCLC, or other non-NSCLC pathological types.
• Known EGFR mutations or ALK positivity, or other actionable driver gene mutations for which approved targeted therapies are available and accessible.
• Presence of malignant pleural effusion. For subjects with drainable pleural effusion during the screening period, at least one thoracentesis is required to rule out the presence of malignant cells.
• Prior systemic anti-cancer therapy for non-small cell lung cancer. If the subject has previously received anti-cancer treatment with traditional Chinese medicine (TCM), enrollment is permitted only if the interval between the completion of TCM therapy and the first dose of study drug is at least 2 weeks.
• Receipt of systemic immunosuppressive therapy within 2 weeks prior to the first dose, or expected need for systemic immunosuppressive medication during the study treatment period.
• Current participation in an interventional clinical study treatment, or receipt of another investigational drug or investigational device within 4 weeks prior to the first dose.
• History of malignancies other than NSCLC within 5 years prior to enrollment.
• Presence of autoimmune disease.
• Subjects with known or suspected interstitial lung disease; other moderate to severe pulmonary diseases that may interfere with the detection or management of drug-related pulmonary toxicity or significantly impair respiratory function, including but not limited to idiopathic pulmonary fibrosis, organizing pneumonia/obstructive bronchiolitis, etc.
• Subjects with severe cardiovascular or cerebrovascular diseases. Clinically significant bleeding symptoms or obvious bleeding tendency within 1 month prior to the first dose.
• Arterial or venous thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism) within 3 months prior to the first dose.
• Congenital or acquired immunodeficiency, including but not limited to human immunodeficiency virus (HIV) infection, active hepatitis B, or hepatitis C.
• Evidence of active tuberculosis infection within 1 year prior to the first dose.
• Severe infection within 4 weeks prior to the first dose.
• Receipt of live attenuated vaccine within 28 days prior to the first dose, or planned receipt of live attenuated vaccine during the study period.
• Major surgery (other than diagnostic procedures or biopsy) within 28 days prior to the first dose.
• History of or planned allogeneic bone marrow transplantation or solid organ transplantation.
• History of severe hypersensitivity reactions to other monoclonal antibodies or fusion proteins, or known allergy to any component of the randomly assigned treatment regimen.
• Female subjects who are pregnant, breastfeeding, or planning to become pregnant during the study period.
• Known history of substance abuse, alcohol abuse, or drug addiction.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Adebrelimab plus recaticimab and chemotherapy	Drug: Adebrelimab, Retlirafusp alfa, Recaticimab and chemotherapy; Adebrelimab/Retlirafusp alfa IV +Recaticimab SC + platinum-based chemotherapy IV, 21-day cycle
Experimental: Arm B; Retlirafusp alfa plus recaticimab and chemotherapy	Drug: Adebrelimab, Retlirafusp alfa, Recaticimab and chemotherapy; Adebrelimab/Retlirafusp alfa IV +Recaticimab SC + platinum-based chemotherapy IV, 21-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR rate	Pathological complete response rate	four weeks after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MPR rate	major pathologic response rate	four weeks after surgery
ORR	objective response rate	from first dose to disease progression or death, whichever comes first, up to 3 years
EFS	event free survival	from first dose to disease progression or death, whichever comes first, up to 3 years
OS	overall survival	from first dose to disease progression or death, whichever comes first, up to 3 years

Collaborators and Investigators

• Sponsor: Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: April 28, 2026
• First Submitted That Met QC Criteria: April 28, 2026
• First Posted (Actual): May 5, 2026

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 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; Therapeutics; Drug Therapy
• Other Study ID Numbers: LGH2026125

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