Clinical Study of a Personalized Neoantigen Cancer Vaccine in Treating Patients With Advanced Malignant Tumor

• ClinicalTrials.gov Identifier: NCT03662815
• Recruitment Status: Active, not recruiting
• First Posted: September 7, 2018
• Last Update Posted: September 4, 2019
• Sponsor: Sir Run Run Shaw Hospital
• Collaborator: Hangzhou Neoantigen Therapeutics Co., Ltd.
• Information provided by (Responsible Party): Yong Fang, Sir Run Run Shaw Hospital

Tracking Information

• First Submitted Date: September 5, 2018
• First Posted Date: September 7, 2018
• Last Update Posted Date: September 4, 2019
• Actual Study Start Date: February 7, 2018
• Estimated Primary Completion Date: March 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 5, 2018)

• Objective Response Rate [ Time Frame: 2 years ]
• Number of participants experiencing clinical and laboratory adverse events (AEs) [ Time Frame: 1 year ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 5, 2018)

• Overall Survival Rate [ Time Frame: 2 years ]
• Progression Free Survival [ Time Frame: 2 years ]

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: September 5, 2018)

• Measurement of CD4/CD8 T lymphocyte subsets [ Time Frame: 2 years ]
• The polypeptide antigen - induced IFN-γ T cells responses [ Time Frame: 2 years ]
• Peripheral blood T cell receptor sequencing analysis [ Time Frame: 2 years ]

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Clinical Study of a Personalized Neoantigen Cancer Vaccine in Treating Patients With Advanced Malignant Tumor
• Official Title: Safety, Tolerability and Partial Efficacy Study of a Personalized Neoantigen Cancer Vaccine inTreating Patients With Advanced Malignant Tumor

Brief Summary

This research study is evaluating a new type of cancer vaccine called "Personalized Neoantigen Cancer Vaccine" as a possible treatment for advanced malignant tumor. The purpose of the clinical study is evaluating the safety, tolerability and partial efficacy of the personalized neoantigen cancer vaccine in the treatment of Chinese patients with advanced malignant cancer, so as to provide a new personalized therapeutic strategy for advanced pancreatic cancer 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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Malignant Solid Tumor

Intervention

• Biological: iNeo-Vac-P01
  Neoantigen peptides
• Other: GM-CSF
  immune adjuvant
  Other Name: granulocyte-macrophage colony stimulating factor

Study Arms

Experimental: iNeo-Vac-P01

Personal Cancer Vaccine: iNeo-Vac-P01 (peptides)+ GM-CSF;

Peptides: 0.1 or 0.3 mg per peptide given on days 1, 4, 8, 15, 22, 78, and 162 for a total of 7 doses. Additional booster vaccines might be administered depending on ethics and patients' potential benefit.

GM-CSF: 40 mcg given 30 minutes before iNeo-Vac-P01.

Interventions:

• Biological: iNeo-Vac-P01
• Other: GM-CSF

Publications *

• Wedén S, Klemp M, Gladhaug IP, Møller M, Eriksen JA, Gaudernack G, Buanes T. Long-term follow-up of patients with resected pancreatic cancer following vaccination against mutant K-ras. Int J Cancer. 2011 Mar 1;128(5):1120-8. doi: 10.1002/ijc.25449.
• Ott PA, Hu Z, Keskin DB, Shukla SA, Sun J, Bozym DJ, Zhang W, Luoma A, Giobbie-Hurder A, Peter L, Chen C, Olive O, Carter TA, Li S, Lieb DJ, Eisenhaure T, Gjini E, Stevens J, Lane WJ, Javeri I, Nellaiappan K, Salazar AM, Daley H, Seaman M, Buchbinder EI, Yoon CH, Harden M, Lennon N, Gabriel S, Rodig SJ, Barouch DH, Aster JC, Getz G, Wucherpfennig K, Neuberg D, Ritz J, Lander ES, Fritsch EF, Hacohen N, Wu CJ. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature. 2017 Jul 13;547(7662):217-221. doi: 10.1038/nature22991. Epub 2017 Jul 5. Erratum in: Nature. 2018 Mar 14;555(7696):402.
• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: September 5, 2018): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2021
• Estimated Primary Completion Date: March 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Must freely sign informed consent;
• Aged 18 to 75 years old;
• The expected survival period is more than 6 months;
• ECOG score is 0 or 1;
• Patients with advanced tumors who fail to receive standard therapy, and those who are not suitable or refuse standard adjuvant therapy;
• Advanced malignant cancer diagnosed by pathology and imageology;
• At least one measurable lesions;
• To be able to obtain sufficient tumor tissue samples and blood samples for analysis, or to have genomic/exon/transcriptional data of tumor tissues and normal tissues, and the data meet the analysis requirements;
• The main organs function is normal, such as the heart, liver and kidney;
• Haematological index:

neutrophil count≥1.5×109/L

hemoglobin≥10g/dL

platelet count≥100×109/L

• Biochemical index:

Total bilirubin is less than or equal to 1.5 times the upper limit of normal value (ULN)

AST and ALT is less than or equal to 2.5 times the upper limit of normal value

Serum creatinine and urea nitrogen (BUN) is less than or equal to 1.5 times the upper limit of normal value

• 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;
• Good compliance, able to follow research protocols and follow-up procedures.

Exclusion Criteria:

• Diagnosed as other malignant tumor, but cured basal cell carcinoma, thyroid carcinoma, cervical dysplasia etc is excluded;
• No neoantigen was found in the sequencing data;
• There have been bone marrow or stem cell transplants;
• Systemic cancer treatment or other drugs under study were treated within 4 weeks prior to individualized tumor targeted polypeptides treatment;
• Received other polypeptide inoculation 4 weeks before treatment; Patients may not be vaccinated with other polypeptides 8 weeks after the last individualized tumor targeted polypeptides trentment;
• Active bacterial or fungal infections identified clinically (>= level 2 of NCI-CTC edition 3);
• Patients with HIV, HCV, HBV infection, severe asthma, autoimmune disease, immunodeficiency or treated with immunosuppressive drugs;
• People infected with herpes virus (scabbed for more than 4 weeks is excluded);
• People infected with respiratory virus (cured for more than 4 weeks is excluded);
• Severe coronary or cerebrovascular disease, or other diseases that the investigators considered should to be exclusion;
• Drug abuse, Clinical, psychological or social factor result in affecting informed consent or research implementation;
• Have a history of drug or polypeptide allergies, or people who are allergic to other potential immunotherapies.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03662815
• Other Study ID Numbers: INEO-P-002
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Yong Fang, Sir Run Run Shaw Hospital
• Study Sponsor: Sir Run Run Shaw Hospital
• Collaborators: Hangzhou Neoantigen Therapeutics Co., Ltd.
• Investigators: Not Provided
• PRS Account: Sir Run Run Shaw Hospital
• Verification Date: September 2018