## Protocol Section
### Identification Module
**NCT ID:** NCT04864379

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

**Official Title:** Safety, Tolerability and Immunogenicity of a Personalized Neoantigen Cancer Vaccine Combined With Anti-PD-1 and Radiofrequency Ablation in Patients With Advanced Solid Tumors

#### Organization Study ID Info
**ID:** INEO-P-003
#### Organization
**Class:** OTHER
**Full Name:** Sir Run Run Shaw Hospital
### Status Module
#### Completion Date
**Date:** 2025-08-03

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2021-04-28

**Type:** ACTUAL

**Last Update Submit Date:** 2021-04-25

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2025-08-03

**Type:** ESTIMATED

#### Start Date
**Date:** 2020-09-03

**Type:** ACTUAL

**Status Verified Date:** 2021-04

#### Study First Post Date
**Date:** 2021-04-28
**Type:** ACTUAL
**Study First Submit Date:** 2021-04-25
**Study First Submit QC Date:** 2021-04-25
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Hangzhou Neoantigen Therapeutics Co., Ltd.

#### Lead Sponsor

**Class:** OTHER

**Name:** Sir Run Run Shaw Hospital

#### Responsible Party

**Investigator Affiliation:** Sir Run Run Shaw Hospital

**Investigator Full Name:** Yong Fang

**Investigator Title:** Chief Physician

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**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 Module

**Conditions:**

- Advanced Malignant Solid Tumor

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 30

**Type:** ESTIMATED

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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.

**Intervention Names:**

- Biological: iNeo-Vac-P01

- Other: GM-CSF

- Drug: PD-1

- Procedure: RFA

**Label:** RFA+PD-1+iNeo-Vac-P01

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** 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.

**Intervention Names:**

- Biological: iNeo-Vac-P01

- Other: GM-CSF

- Drug: PD-1

- Procedure: RFA

**Label:** RFA+iNeo-Vac-P01+PD-1

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

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

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

**Description:** iNeo-Vac-P01: 300 mcg per peptide

**Name:** iNeo-Vac-P01

**Other Names:**

- Neoantigen peptides

**Type:** BIOLOGICAL

#### Intervention 2

**Arm Group Labels:**

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

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

**Description:** GM-CSF: 40 mcg

**Name:** GM-CSF

**Other Names:**

- immune adjuvant

- granulocyte-macrophage colony stimulating factor

**Type:** OTHER

#### Intervention 3

**Arm Group Labels:**

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

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

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

**Name:** PD-1

**Other Names:**

- PD-1 inhibitor

**Type:** DRUG

#### Intervention 4

**Arm Group Labels:**

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

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

**Description:** Radiofrequency ablation surgery

**Name:** RFA

**Other Names:**

- Radiofrequency ablation

**Type:** PROCEDURE

### Outcomes Module

#### Primary Outcomes

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

**Measure:** Number of participants experiencing clinical and laboratory adverse events (AEs)

**Time Frame:** 1 year

**Description:** 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.

**Measure:** Objective Response Rate

**Time Frame:** 5 years

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

**Measure:** Measurement of CD4/CD8 T lymphocyte subsets.

**Time Frame:** 3 years

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

**Measure:** The IFN-γ T cells responses induced by neoantigen

**Time Frame:** 2 years

#### Secondary Outcomes

**Description:** Time from surgery to death or last follow-up.

**Measure:** Overall Survival(OS)

**Time Frame:** 5 years

**Description:** Time from surgery to any progression.

**Measure:** Progression-free Survival(PFS)

**Time Frame:** 3 years

**Description:** The diversity and clonability of T cells were analyzed by peripheral blood T cell receptor sequencing.

**Measure:** Peripheral blood T cell receptor sequencing analysis

**Time Frame:** 2 years

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Must freely sign informed consent;
2. Aged 18 to 75 years old;
3. Life expectancy of greater than 3 months.
4. At least one measurable lesion according to RECIST 1.1 criteria(Radiofrequency ablation of lesions was excluded).
5. histologically confirmed Advanced solid tumors,
6. have failed standard treatment, or unsuitable to receive standard treatment
7. Liver metastases are present and are suitable for radiofrequency ablation；
8. agreeable to allow tumor and normal samples to be submitted for complete exome and transcription sequencing.
9. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
10. Good hematopoietic function ， defined as absolute neutrophils count ≥1.5×109 /L, platelet count ≥100 ×109 /L, and hemoglobin ≥90g/L；
11. 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;
12. 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;
13. 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；
14. 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;

Exclusion Criteria:

1. 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;
2. Major surgical treatment within 3 weeks prior to first administration;
3. Completed palliative radiotherapy within 7 days prior to first administration;
4. Clinical active diverticulitis, abdominal abscess, and gastrointestinal obstruction;
5. Have none suitable neoantigen;
6. Have been bone marrow or stem cell transplants;
7. Clinically uncontrollable pleural effusion/peritoneal effusion/pericardial effusion;
8. Severe known allergic reactions (≥ grade 3) to the active ingredient and/or any excipient of PD-1 monoclonal antibody；
9. Active autoimmune disease requiring systemic treatment occurred within 2 years prior to initial administration；
10. 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；
11. Full recovery from toxicity and/or complications associated with any intervention has not been achieved prior to the commencement of treatment；
12. 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;
13. Symptoms of central nervous metastasis
14. A history of noninfectious pneumonia requiring glucocorticoid therapy or current interstitial lung disease within 1 year prior to initial administration;
15. Active infections that require systemic treatment;
16. A known presence of mental illness or substance abuse conditions that may affect compliance with the test requirements;
17. Human immunodeficiency virus (HIV) infection；
18. Untreated active hepatitis B；
19. Active subjects with HCV infection；
20. vaccine was administered within 30 days prior to initial administration (cycle 1, day 1)；
21. Medical history or evidence of disease, abnormal values of treatment or laboratory tests, or other conditions deemed inappropriate by the Investigator to interfere with the results of the study, prevent subjects from participating fully in the study;
22. breastfeeding women. Patients with previous and current objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severe pulmonary impairment, etc.;
23. Patients whose cardiopulmonary function cannot tolerate anesthesia；
24. The investigator evaluates other circumstances that may affect the conduct of the clinical study and the judgment of the study results.

**Maximum Age:** 75 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** 307480770@qq.com

**Name:** Fang Yong, MD, PhD

**Phone:** +86-571-87887821

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Hangzhou

**Contacts:**

***Contact 1:***

- **Email:** 307480770@qq.com

- **Name:** Fang Yong, MD, PhD

- **Phone:** +86-571-87887821

- **Role:** CONTACT

***Contact 2:***

- **Name:** Fang Yong, MD, PhD

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** China

**Facility:** Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine

**State:** Zhejiang

**Status:** RECRUITING

**Zip:** 310000

### References Module

#### References

**Citation:** 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

**Citation:** 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

## Derived Section

### Condition Browse Module - Meshes

- ID: D000009369

- Term: Neoplasms

### Intervention Browse Module - Ancestors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000074322

- Term: Antineoplastic Agents, Immunological

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000007155

- Term: Immunologic Factors

- ID: D000045505

- Term: Physiological Effects of Drugs

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: ANeo

- Name: Antineoplastic Agents

### Intervention Browse Module - Browse Leaves

- ID: M17360

- Name: Vaccines

- Relevance: LOW

- As Found: Unknown

- ID: M257633

- Name: Molgramostim

- Relevance: HIGH

- As Found: Button

- ID: M219218

- Name: Sargramostim

- Relevance: HIGH

- As Found: Button

- ID: M3628

- Name: Adjuvants, Immunologic

- Relevance: LOW

- As Found: Unknown

- ID: M2342

- Name: Immune Checkpoint Inhibitors

- Relevance: HIGH

- As Found: Escitalopram

- ID: M1346

- Name: Antineoplastic Agents, Immunological

- Relevance: LOW

- As Found: Unknown

- ID: M10201

- Name: Immunologic Factors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000082082

- Term: Immune Checkpoint Inhibitors

- ID: C000082430

- Term: Molgramostim

- ID: C000081222

- Term: Sargramostim

### Misc Info Module

- Version Holder: 2024-05-24
