Adebrelimab or Retlirafusp Alfa Plus Recaticimab and Chemotherapy for Resectable NSCLC

Official title

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

Overview

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.

Interventions

• Drug Adebrelimab, Retlirafusp alfa, Recaticimab and chemotherapy
  Adebrelimab/Retlirafusp alfa IV +Recaticimab SC + platinum-based chemotherapy IV, 21-day cycle

Primary outcome measures

• pCR rate [Time frame: four weeks after surgery]

Secondary outcome measures (4)

• MPR rate [Time frame: four weeks after surgery]
• ORR [Time frame: from first dose to disease progression or death, whichever comes first, up to 3 years]
• EFS [Time frame: from first dose to disease progression or death, whichever comes first, up to 3 years]
• OS [Time frame: from first dose to disease progression or death, whichever comes first, up to 3 years]

Eligibility criteria

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.

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07567326 · LGH2026125

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗