ICI Rechallenge for Advanced NSCLC With Long-Term Response to First-Line ICI

A Multicenter, Single-Arm Pilot Study of Immune Checkpoint Inhibitors in Patients With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer Who Had Long-Term (Two Years or Longer) Response to First-Line Immunotherapy

An exploratory phase II trial of immune checkpoint inhibitors (ICIs, anti-PD-1/anti-PD-L1) as second-line treatment with advanced non-small cell lung cancer (NSCLC) who had long-term response to first-line immunotherapy (with or without chemotherapy).

This study aims to evaluate efficacy and safety of ICI rechallenge in long-term responders to prior ICI. Furthermore, it seeks to identify biomarkers capable of predicting the efficacy of immunotherapy and prognosis.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Immune checkpoint inhibitor

Detailed Description

This is a multi-center study. The study plans to include a total of 27 advanced NSCLCs who had benefited from first-line immunotherapy over two years before disease progression.

Participants will receive up to 17 cycles of ICI (anti-PD-1 or anti-PD-L1) monotherapy.

Optional ICI monotherapy regimens include: Pembrolizumab 200mg every 3 weeks, or Tislelizumab 200mg every 3 weeks, or Camrelizumab 200mg every 3 weeks, or Toripalimab 240mg every 3 weeks.

The outcomes including efficacy and safety will be examined. Additionally, peripheral blood samples will be collected before treatment, and at the 6th, 12th, and 24th weeks after treatment initiation to explore biomarkers for immunotherapy. Also it is highly recommended to collect pretreatment tumor tissue from patients.

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mengzhao Wang, MD.; Phone Number: +8613911235467; Email: mengzhaowang@sina.com
• Study Contact Backup: Name: Minjiang Chen, MD.; Phone Number: +8618618340880; Email: minjiangchen@163.com

Study Locations

• China
  • Beijing, China, 100730
    • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Participants must have a thorough understanding of this study and voluntarily sign an informed consent form (ICF);
2. Age between 18 and 80 years, any gender;
3. Histologically or cytologically confirmed stage III-IV non-small cell lung cancer (NSCLC);
4. Previous treated with first-line immunotherapy (immunotherapeutic agents include currently marketed anti-PD-L1 or anti-PD-1 monoclonal antibodies: pembrolizumab, nivolumab, atezolizumab, durvalumab, tislelizumab, toripalimab, sintilimab, camrelizumab, etc.; investigational drugs not yet marketed need discussion with the study team prior to enrollment; with or without platinum-based doublet chemotherapy) for at least 35 cycles or disease stability confirmed by imaging assessment for at least 2 years, and disease progression;
5. Measurable disease (at least 1 lesion) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1);
6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2;

7. Adequate organ function:

   Hematology: Absolute neutrophil count (ANC) ≥1500/μL; Platelets ≥100000/μL; Hemoglobin ≥9.0g/dL; Renal: Serum creatinine ≤1.5×ULN or calculated creatinine clearance (CrCl) ≥60 mL/min (using Cock-Gault formula); Hepatic: Total bilirubin ≤1.5 ×ULN or, for subjects with total bilirubin levels >1.5×ULN, direct bilirubin within normal limits; AST (SGOT) and ALT (SGPT) ≤2.5×ULN; Coagulation: International normalized ratio (INR) or prothrombin time (PT), activated partial thromboplastin time (APTT) ≤1.5×ULN;

8. Subjects must be willing and able to comply with study visits, treatment plans, laboratory tests, and other study procedures;
9. Female subjects of childbearing potential and male subjects with female partners of childbearing potential must agree to use highly effective contraception during the study and for 180 days after the last dose of the study drug.

Exclusion Criteria:

1. Received two or more prior systemic therapies;
2. Known sensitive EGFR mutation (EGFR exon19 del or EGFR exon21 L858R) or ALK rearrangement;
3. Symptomatic or progressing CNS metastases, leptomeningeal metastases;
4. History of autoimmune disease, active autoimmune disease, immunodeficiency, or requiring systemic corticosteroid/immunosuppressive therapy; (except: a history of hypothyroidism; well-controlled stable type I diabetes mellitus);
5. Idiopathic pulmonary fibrosis (including interstitial pneumonia), drug-induced pneumonitis, history of (non-infectious) pneumonia/interstitial lung disease requiring steroid therapy;
6. Known active tuberculosis, human immunodeficiency virus (HIV) infection; active hepatitis B (defined as positive HBsAg or positive hepatitis B virus DNA test result above the detection limit) or hepatitis C (defined as known positive HCV antibody result, known quantitative HCV-RNA analysis result above the detection limit) history; other known active infections requiring systemic therapy;
7. Received systemic immunostimulatory therapy within 4 weeks before initiation of study treatment or within 5 half-lives of the drug (whichever is longer);
8. Pregnancy, lactation, planning to become pregnant, or fathering a child during the anticipated duration of the study (from screening visit to 180 days after the last dose of investigational drug);
9. Prior allogeneic tissue/organ transplantation and other conditions unsuitable for immunotherapy.

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: Immunotherapy; Immune checkpoint inhibitor (anti-PD/1 or anti-PD-L1) monotherapy	Drug: Immune checkpoint inhibitor; Physician's choice immunotherapy with one of the following every 21 days until disease progression or intolerable toxicity or up to 17 cycles: Pembrolizumab 200mg;; Tislelizumab 200mg;; Camrelizumab 200mg;; Toripalimab 240mg.; Other Names: Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	Time from the date of treatment start to date of disease progression met by RECIST 1.1 or death from any cause.	5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Time from the date of treatment start to date of death from any cause.	24 months
Objective Response Rate (ORR)	Proportion of patients with complete and partial responses to immunotherapy according to RECIST 1.1.	5 months
Progression Free Survival 2 (PFS 2)	Time from the date of treatment start to the date of disease progression or death after initiation of subsequent anti-tumor therapy.	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety profile	Evaluate adverse events of any cause, treatment-related adverse events, immune-mediated adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	24 months

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Principal Investigator: Minjiang Chen, MD., Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 10, 2024
• Primary Completion (Estimated): January 10, 2027
• Study Completion (Estimated): December 10, 2027

Study Registration Dates

• First Submitted: April 24, 2024
• First Submitted That Met QC Criteria: April 24, 2024
• First Posted (Actual): April 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors
• Other Study ID Numbers: CAPTRAL2024v1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The result of the study and all the supporting informations will be shared in the form of publishing article.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No