A Phase II Trial to Evaluate the Efficiency and Safety of Serplulimab Plus Chemotherapy as Conversion Therapy in NSCLC

Official title

A Phase II Trial to Evaluate the Efficiency and Safety of Serplulimab Plus Chemotherapy as Conversion Treatment for Patients With Stage IIIB-IVA Oligometastatic Non-small Cell Lung Cancer

Overview

This is a phase II, single-arm study to evaluate the efficacy and safety of Serplulimab plus chemotherapy as conversion treatment in patients with stage IIIB-IVA oligometastatic non-small cell lung cancer.

Detailed description

This single-arm, open-label, prospective phase II clinical trial was designed to evaluate the efficacy and safety of Serplulimab plus chemotherapy as conversion treatment in patients with stage IIIB-IVA oligometastatic non-small cell lung cancer.

The primary endpoints were the rate of NSCLC converting to resectable tumors and the 1-year progression-free survival (PFS) rate.The secondary endpoints included the rates of R0 resection, major pathological response (MPR) and pathological complete response (pCR), overall survival (OS) and PFS. Multi-omics analysis will be performed to identify potential biomarkers for treatment response.

Interventions

• Procedure serplulimab plus chemotherapy as conversion treatment
  Patients with unresectable NSCLC will receive serplulimab plus chemotherapy as conversion treatment, and then curative pneumonectomy will be provided for patients who are suitable for primary tumor resection. Locoregional ablative treatments will be performed for metastatic lesions.

Primary outcome measures

• the rate of NSCLC converting to resectable tumors [Time frame: up to 16 weeks]
• the 1-year progression-free survival (PFS) rate [Time frame: up to one year]

Secondary outcome measures (5)

• the rate of R0 resection [Time frame: immediately after the surgery]
• Progression-free survival (PFS) [Time frame: up to five years]
• Overall survival (OS) [Time frame: up to five years]
• the rate of major pathological response (MPR) [Time frame: up to 16 weeks]
• the rate of pathological complete response (pCR) [Time frame: up to 16 weeks]

Eligibility criteria

Inclusion criteria

• Patients should voluntarily join this study and sign the informed consent form
• NSCLC patients diagnosed by cytology or histology and not previously receiving anti-tumor treatments (including systemic treatments, local treatments .etc)
• Patients with IIIB - IVA oligometastatic NSCLC : (a) IIIB - IIIC stage (T1-4N2-3): patients are not suitable or refuse to receive upfront surgical resection or radiotherapy; (b) oligometastatic stage IV (T1-3N0-2): radical resection/radiotherapy is feasible for metastatic lesions (the number of metastases being up to 3, and the maximum diameter of metastases being up to 2cm)
• After evaluation by MDT, upfront surgical resection is not the preferred treatment, but after induction systemic treatments, radical resection of the primary tumor is feasible, and radical resection/radiotherapy is feasible for extrathoracic metastases (if any)
• Age from 18 to 75 years old, both male and female
• ECOG score 0-1
• According to the RECIST v1.1 , patients should have at least one measurable lesion
• For suspicious mediastinal lymph nodes (including pathological enlargement or PET-CT indicating malignancy, etc.), further sampling is required for pathological diagnosis by EUBS, thoracoscopy, or mediastinoscopy
• According clinical evaluation, the lung function of patients (such as FVC, FEV1, TLC, FRC, DLco, etc.) should be sufficient for pneumonectomy
• The function of important organs should meet the following requirements: absolute count of neutrophils ≥ 1.5 × 109/L； Platelets ≥ 100 × 109/L； Hemoglobin ≥ 90g/L; Serum albumin ≥ 35g/L; Thyroid hormone (TSH) ≤ 1 × ULN； Serum bilirubin ≤ 1.5 × ULN； ALT and AST ≤ 3 × ULN； International standardized ratio (INR) ≤ 1.5 or prothrombin time (PT) ≤ 1.5 × ULN； Serum creatinine ≤ 1.5 × ULN
• Female patients at childbearing age are required to use contraceptive measures; for male patients whose partners are women at childbearing age, effective methods of contraception should be used during the trial period

Exclusion criteria

Patients who meet any of the following conditions will not be enrolled in this study:

• NSCLC patients have sensitive EGFR mutation, EML4-ALK fusion or other forms of ALK gene changes
• Patients have previously received immune checkpoint inhibitors such as PD-1/ PD-L1/CTLA4 antibody
• Patients with other primary malignancies within the past 3 years (excluding cured skin basal cell carcinoma and cervical carcinoma in situ)
• Patients with active hepatitis B/C
• Patients with any active autoimmune diseases or a history of autoimmune diseases
• Patients who are using immunosuppressive agents or require systemic hormone therapy
• Patients with hypertension but without good control even through antihypertensive medication treatment ; patients with clinical symptoms or diseases related to unsatisfying cardiac function
• Patients with abnormal coagulation function (INR>2.0, PT>16s)
• Arterial/venous thrombotic events occurred before screening within 6 months
• Patients with active infection
• Patients with congenital or acquired immune dysfunction (such as HIV infection)
• According to the judgment of the researchers, patients have other factors that may affect the results of the research or cause the research to be terminated

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

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Zhejiang University — Hangzhou

Identifiers

NCT: NCT05837052 · CTHLX10

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗