Clinical Study of a Personalized Neoantigen Cancer Vaccine Combined With Anti-PD-1 and RFA in Patients With Solid Tumors

NCT04864379 | Unknown Phase 1

• 1 other identifier: INEO-P-003
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is evaluating a new type of personalized neoantigen cancer vaccine（iNeo-Vac-P01）combined with anti-PD-1 antibody and radiofrequency ablation as a possible treatment for patients with advanced solid tumors. The primary objective of this trial is to evaluate safety, tolerability and immunogenicity of iNeo-Vac-P01 in combination with anti-PD-1 and radiofrequency ablation, so as to provide a new personalized therapeutic strategy for patients. It is known that cancer patients have mutations (changes in genetic material) that are specific to an individual patient and tumor. These mutations can cause the tumor cells to produce proteins that appear very different from the body's own cells. It is possible that these proteins used in a vaccine may induce strong immune responses, which may help the participant's body fight any tumor cells that could cause the cancer to come back in the future. The study will examine the safety of the vaccine when given at several different time points and will examine the participant's blood cells for signs that the vaccine induced an immune response.

Conditions

Advanced Malignant Solid Tumor

Outcome Measures

Primary Outcomes (4)

• Number of participants experiencing clinical and laboratory adverse events (AEs)

  Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0.

  1 year

• Objective Response Rate

  ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study.

  5 years

• Measurement of CD4/CD8 T lymphocyte subsets.

  CD4/CD8 T lymphocyte subsets were detected by flow cytometry.

  3 years

• The IFN-γ T cells responses induced by neoantigen

  The response of IFN-γ T cells induced by neoantigen was detected by ELispot.

  2 years

Secondary Outcomes (3)

• Overall Survival(OS)

  5 years

• Progression-free Survival(PFS)

  3 years

• Peripheral blood T cell receptor sequencing analysis

  2 years

Study Arms (2)

RFA+PD-1+iNeo-Vac-P01

EXPERIMENTAL

Patients will undergo radiofrequency ablation. At Week 3, patients will receive PD-1 at a dose of 200mg administered by intravenous infusion (IV) every 2 weeks. At Week 12,all patients,regardless of their disease status,iNeo-Vac-P01(300mcg per peptide)+ GM-CSF (40mcg) on days 1, 4, 8, 15, 22, 52, and 82 from week 12. Additional booster vaccines might be administered depending on ethics and patients' potential benefit.

Biological: iNeo-Vac-P01; Other: GM-CSF; Drug: PD-1; Procedure: RFA

RFA+iNeo-Vac-P01+PD-1

EXPERIMENTAL

Patients will undergo radiofrequency ablation. At Week 12, patients will receive iNeo-Vac-P01(300mcg per peptide)+ GM-CSF (40mcg) on days 1, 4, 8, 15, 22, 52, and 82 from week 12. Additional booster vaccines might be administered depending on ethics and patients' potential benefit. At Week 16, patients,regard of their disease status,will receive PD-1 at a dose of 200mg administered by intravenous infusion (IV) every 2 weeks.

Biological: iNeo-Vac-P01; Other: GM-CSF; Drug: PD-1; Procedure: RFA

Interventions

iNeo-Vac-P01 BIOLOGICAL

iNeo-Vac-P01: 300 mcg per peptide

Also known as: Neoantigen peptides

RFA+PD-1+iNeo-Vac-P01; RFA+iNeo-Vac-P01+PD-1

GM-CSF OTHER

GM-CSF: 40 mcg

Also known as: immune adjuvant, granulocyte-macrophage colony stimulating factor

RFA+PD-1+iNeo-Vac-P01; RFA+iNeo-Vac-P01+PD-1

PD-1 DRUG

PD-1: 200mg administered by intravenous infusion every 2 weeks.

Also known as: PD-1 inhibitor

RFA+PD-1+iNeo-Vac-P01; RFA+iNeo-Vac-P01+PD-1

RFA PROCEDURE

Radiofrequency ablation surgery

Also known as: Radiofrequency ablation

RFA+PD-1+iNeo-Vac-P01; RFA+iNeo-Vac-P01+PD-1

Eligibility Criteria

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

You may qualify if:

• Must freely sign informed consent;
• Aged 18 to 75 years old;
• Life expectancy of greater than 3 months.
• At least one measurable lesion according to RECIST 1.1 criteria(Radiofrequency ablation of lesions was excluded).
• histologically confirmed Advanced solid tumors,
• have failed standard treatment, or unsuitable to receive standard treatment
• Liver metastases are present and are suitable for radiofrequency ablation；
• agreeable to allow tumor and normal samples to be submitted for complete exome and transcription sequencing.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
• Good hematopoietic function ， defined as absolute neutrophils count ≥1.5×109 /L, platelet count ≥100 ×109 /L, and hemoglobin ≥90g/L；
• Good liver function, defined as total bilirubin levels ≤1.5 times the upper normal limit (ULN), and glutamic-oxalacetic transaminase (AST) and glutamic-pyruvic transaminase (ALT) levels ≤5 times ULN;
• Good renal function, defined as serum creatinine ≤1.5 times ULN or calculated creatinine clearance ≥ 60 mL /min (Cockcroft-Gault formula); Routine urine examination urine protein less than 2+, or 24 hours urine protein quantitative \<1g;
• Good coagulation function, defined as INR or prothrombin time (PT) ≤1.5 times ULN; If the subject is receiving anticoagulant therapy, PT is acceptable as long as it is within the range of anticoagulant drug use；
• Pregnant, lactating women and women of child-bearing age must have a negative pregnancy test within 7 days before entering the group, and short-term have no fertility plan, and are willing to take protective measures (contraception or other birth control methods) before and during the clinical trial;

You may not qualify if:

• Currently participating in an interventional clinical study treatment or has received other investigational drugs or used investigational devices within 4 weeks prior to the first administration;
• Major surgical treatment within 3 weeks prior to first administration;
• Completed palliative radiotherapy within 7 days prior to first administration;
• Clinical active diverticulitis, abdominal abscess, and gastrointestinal obstruction;
• Have none suitable neoantigen;
• Have been bone marrow or stem cell transplants;
• Clinically uncontrollable pleural effusion/peritoneal effusion/pericardial effusion;
• Severe known allergic reactions (≥ grade 3) to the active ingredient and/or any excipient of PD-1 monoclonal antibody；
• Active autoimmune disease requiring systemic treatment occurred within 2 years prior to initial administration；
• Diagnosed with immunodeficiency or was receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dosing of the study；
• Full recovery from toxicity and/or complications associated with any intervention has not been achieved prior to the commencement of treatment；
• Other tumors diagnosed within 5 years prior to initial administration, exceptions include radical basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or radical resection of carcinoma in situ;
• Symptoms of central nervous metastasis
• A history of noninfectious pneumonia requiring glucocorticoid therapy or current interstitial lung disease within 1 year prior to initial administration;
• Active infections that require systemic treatment;

Sponsors & Collaborators

• Sir Run Run Shaw Hospital: lead
• Hangzhou Neoantigen Therapeutics Co., Ltd.: collaborator

Study Sites (1)

Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

RECRUITING

Related Publications (2)

• Fang Y, Mo F, Shou J, Wang H, Luo K, Zhang S, Han N, Li H, Ye S, Zhou Z, Chen R, Chen L, Liu L, Wang H, Pan H, Chen S. A Pan-cancer Clinical Study of Personalized Neoantigen Vaccine Monotherapy in Treating Patients with Various Types of Advanced Solid Tumors. Clin Cancer Res. 2020 Sep 1;26(17):4511-4520. doi: 10.1158/1078-0432.CCR-19-2881. Epub 2020 May 21.

  PMID: 32439700 BACKGROUND

• Ott PA, Hu-Lieskovan S, Chmielowski B, Govindan R, Naing A, Bhardwaj N, Margolin K, Awad MM, Hellmann MD, Lin JJ, Friedlander T, Bushway ME, Balogh KN, Sciuto TE, Kohler V, Turnbull SJ, Besada R, Curran RR, Trapp B, Scherer J, Poran A, Harjanto D, Barthelme D, Ting YS, Dong JZ, Ware Y, Huang Y, Huang Z, Wanamaker A, Cleary LD, Moles MA, Manson K, Greshock J, Khondker ZS, Fritsch E, Rooney MS, DeMario M, Gaynor RB, Srinivasan L. A Phase Ib Trial of Personalized Neoantigen Therapy Plus Anti-PD-1 in Patients with Advanced Melanoma, Non-small Cell Lung Cancer, or Bladder Cancer. Cell. 2020 Oct 15;183(2):347-362.e24. doi: 10.1016/j.cell.2020.08.053.

  PMID: 33064988 BACKGROUND

MeSH Terms

Interventions

Granulocyte-Macrophage Colony-Stimulating Factor; Adjuvants, Immunologic; Colony-Stimulating Factors; Immune Checkpoint Inhibitors; Radiofrequency Ablation

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Immunologic Factors; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Radiofrequency Therapy; Therapeutics; Ablation Techniques; Surgical Procedures, Operative

Central Study Contacts

Fang Yong, MD, PhD

CONTACT

+86-571-87887821; 307480770@qq.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: April 25, 2021
• First Posted: April 28, 2021
• Study Start: September 3, 2020
• Primary Completion: August 3, 2025
• Study Completion: August 3, 2025
• Last Updated: April 28, 2021

Record last verified: 2021-04

Locations

CN (1)