Personalized Neoantigen MRNA Vaccine Combined with Adebrelimab in Non-Small Cell Lung Cancer Patients

NCT06685653 | Not Yet Recruiting Early Phase 1

• 1 other identifier: NSCLC-IIT-RGL-270-TYS
• Study Type: interventional
• Target: 65
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a phase IIT , it is an open-label study designed to evaluate the safety and tolerability of personalized mRNA tumor vaccine RGL-270 targeting tumor-specific neoantigens and Adebrelimab (a humanized PD-L1 monoclonal antibody) in patients with resectable NSCLC and those with NSCLC who have relapsed or metastasized after first-line standard therapy.

Conditions

NSCLC

Keywords

NSCLC; Personalized mRNA tumor vaccine

Outcome Measures

Primary Outcomes (2)

• • Incidence of DLTs

  • Incidence of DLTs during the observation period of dose-limiting toxicities (DLTs).

  21 days after first administration of RGL-270 in combination with Adebrelimab

• • Safety endpoints

  laboratory indicators, 12-lead ECG, United States Eastern Cooperative Oncology Group (ECOG) performance status score, physical examination, vital signs, adverse events/serious adverse events (AEs/SAEs, severity according to NCI-CTCAE v5.0 criteria)

  90 days (± 7 days) after the last vaccine/adebelimab treatment or 30 days (±7 days) after the last chemotherapy

Secondary Outcomes (5)

• Change from baseline of LNPs

  18 months/24 months after the first dose

• Change from baseline of neoantigen-specific T cell

  18 months/24 months after the frst dose

• Change from baseline of ADA

  18 months/24 months after the frst dose

• The DFS, OS, DFS rate and OS rate in Resectable NSCLC

  18 months/24 months after the frst dose

• The ORR, DoR, PFS and OS in Advanced NSCLC

  18 months/24 months after the frst dose

Study Arms (2)

Part A: Resectable NSCLC subjects

EXPERIMENTAL

Biological: Adebrelimab+RGL-270

Part B: NSCLC subjects with disease recurrence or metastasis after first-line standard therapy

EXPERIMENTAL

Biological: Adebrelimab+RGL-270/single RGL-270

Interventions

Adebrelimab+RGL-270 BIOLOGICAL

Drug: Adebrelimab Adebrelimab is a programmed death-ligand 1 antibody. Drug: RGL-270 RGL-270 is a mRNA tumor vaccines

Part A: Resectable NSCLC subjects

Adebrelimab+RGL-270/single RGL-270 BIOLOGICAL

Drug: Adebrelimab Adebrelimab is a programmed death-ligand 1 antibody. Drug: RGL-270 RGL-270 is a mRNA tumor vaccines

Part B: NSCLC subjects with disease recurrence or metastasis after first-line standard therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Part A \& Part B
• Subjects should understand and comply with the relevant procedures of the study, and voluntarily sign the pre-screening informed consent form;
• Age 18-75 years old (including boundary value), gender is not limited;
• Willing to provide tumor tissue specimens for genetic testing and neoantigen analysis;
• United States Eastern Cooperative Oncology Group (ECOG) score: 0 or 1 point;
• Estimated survival ≥ 6 months;
• Willing to provide blood samples required for the detection of immunogenicity and biomarkers before and after treatment, of which the blood samples for genetic testing during the screening period must be free of blood transfusions, blood products and other hematopoietic stimulating factors within 7 days before collection;
• Vital organ function meets the following criteria (no use of any blood components and cell growth factors within 14 days prior to initiation of study treatment):
• ① Routine blood count: neutrophil count (ANC) ≥ 1.5×109/L, lymphocyte count (LYM) ≥0.5×109/L, platelet count (PLT) ≥1× lower limit of normal (LLN), hemoglobin (Hb) ≥90g/L;
• ② Blood biochemistry: total bilirubin (TBIL) ≤ 1.5× upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5× ULN, serum albumin (ALB) ≥30g/L, serum creatinine (Scr) ≤ 1×ULN;
• ③ Coagulation routine: international normalized ratio (INR) ≤ 1.5, activated partial thromboplastin time (APTT) ≤ 1.5×ULN;
• ④ Cardiac function: left ventricular ejection fraction (LVEF) ≥50%;
• ⑤ ECG: Fridericia's corrected QT interval (QTcF) \<470 msec; The QTc interval must be corrected according to Fridericia's criteria by the formula QTcF = QT/RR\^0.33.
• Female subjects of childbearing potential must have a serum pregnancy test within 7 days prior to the first dose with a negative result; and must be non-lactating;
• Female subjects of childbearing potential and male subjects whose partners are women of childbearing potential must agree to comply with contraceptive requirements from the time of signing the informed consent form until 90 days after the end of the last treatment session (see "Contraceptive Methods" in Annex V for details).

You may not qualify if:

• Part A \& Part B
• Histologically or cytologically confirmed small cell carcinoma (SCLC), mixed SCLC and NSCLC, or other non-NSCLC;
• Carriers of driver mutations (including but not limited to EGFR and ALK gene alterations) for which targeted drugs have been approved for marketing and are accessible;
• Received immune cell or tumor vaccine treatment, including but not limited to tumor-infiltrating lymphocytes (TILs), chimeric antigen receptor T cells (CAR-T), T cell receptor chimeric T cells (TCR-T), and therapeutic tumor vaccines;
• Administration of live attenuated vaccine within 28 days prior to the screening period or planned administration during the study and within 90 days after the end of study drug treatment (inactivated vaccine is allowed);
• Any person who is not suitable for immunotherapy as assessed by the investigator;
• Presence of autoimmune diseases, except for hypothyroidism requiring hormone replacement therapy due to autoimmune thyroiditis;
• Evidence of active tuberculosis infection within 1 year prior to the screening period, regardless of treatment;
• Subjects with a known history of interstitial pneumonia or a high suspicion of interstitial pneumonia, or evidence of active interstitial pneumonia on chest CT during the screening period; Known history of idiopathic pulmonary fibrosis, history of organizing pneumonia (e.g., bronchiolitis obliterans or cryptogenic organizing pneumonia);
• Concurrent severe infection within 28 days prior to the screening period (such as the need for intravenous infusion of antibiotics, antifungal or antiviral drugs according to clinical diagnosis and treatment standards), or the presence of active infection requiring intravenous infusion of antibiotics during the screening period;
• Presence of clinically uncontrolled pleural effusion or ascites requiring thoracentesis or paracentesis drainage within 14 days prior to the screening period;
• Known allergy to the study drug or any of its excipients, or history of severe allergic reactions to other vaccines;
• History of other malignancies within the past 5 years, excluding cured carcinoma in situ of the cervix, basal cell carcinoma of the skin or squamous cell carcinoma of the skin, localized prostate cancer after radical resection, ductal carcinoma in situ after radical resection (hormonal therapy for non-metastatic prostate cancer or breast cancer is allowed), and papillary thyroid carcinoma;
• Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
• Patients with congenital or acquired immunodeficiencies, such as cellular immunodeficiencies (e.g., DiGeorge syndrome, T-negative severe combined immunodeficiency \[SSCID\]) or combined T-cell and B-cell immunodeficiencies (e.g., T- and B-negative combined immunodeficiency, Wiskott-Aldrich syndrome, ataxia telangiectasia, common variable immunodeficiency); or human immunodeficiency virus (HIV) infection;

Sponsors & Collaborators

• Nanjing Tianyinshan Hospital: lead
• Jilin Provincial Cancer Hospital: collaborator

Central Study Contacts

Yong Song

CONTACT

86 13851761392; yong.song@nju.edu.cn

Wenshu Qu

CONTACT

quws1980@163.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2024
• First Posted: November 12, 2024
• Primary Completion (Estimated): November 30, 2026
• Last Updated: November 12, 2024

Record last verified: 2024-11