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In dose escalation phase, subject will only receive personalized neoantigen tumor vaccine. In dose expansion phase, subject will receive personalized neoantigen tumor vaccine combination with PD-1.

Biological: neoantigen tumor vaccine with or without PD-1 In dose escalation phase, subjects will receive neoantigen tumor vaccine only. In dose expansion phase, subjects will receive neoantigen tumor vaccine combination with PD-1

Personalized neoantigen tumor vaccine

Chunmei Bai, Dr.

YueJuan Cheng

This trial is an investigator-initiated, single-center, open-label, single-arm exploratory study of mRNA personalized neoantigen tumor vaccine in the treatment of advanced solid tumors, including two phases: dose escalation and dose expansion. The main objective is to evaluate the safety and tolerability of personalized neoantigen tumor vaccine in subjects with advanced solid tumors, and secondary objective is to preliminarily evaluate the efficacy of personalized neoantigen tumor vaccine in subjects with advanced solid tumors. According to the characteristics of safety and efficacy data in the dose escalation phase, the dose expansion is performed at the intended clinical dose based on the investigator's judgment, and the treatment will be performed in combination with PD-1 to further evaluate the efficacy and safety profile of personalized neoantigen tumor vaccine at a specific dose.

Both the dose escalation phase and dose expansion phase include a screening period (Week -4 \~ Week -2), a baseline period (Week -1 \~ Day -1), a treatment period (Day 1 \~ Week 8 or 16), and a follow-up period. Subjects who signed and provided the formal informed consent entered the screening period. The treatment period included the initial treatment period (Day 1 \~ Week 8) and the enhanced treatment period (Week 12 \~ Week 16). The investigator determine if the subject is suitable to enter the enhanced treatment period based on the comprehensive judgment of the subject's efficacy, safety, compliance and other factors.

Dose escalation phase is the traditional 3 + 3 design,, 12-18 subjects are expected to be enrolled at 100 μg, 200 μg and 400 μg (3-6 subjects in each group). The low dose group will be enrolled first.

The investigator will choose the optimal clinical dose for dose expansion, which can be one dose group or multiple dose groups. PD-1 will be administered in parallel to further confirm the efficacy and safety of neoantigen tumor vaccine. About 18 subjects will be enrolled. The usage and dosage of PD-1 should aligned with the package insert.

The traditional 3+3 design will be used in dose escalation.

Safety and Efficacy of Personalized Neoantigen Vaccine in Advanced Solid Tumors

A Dose-Escalation and Dose-Expansion Study Evaluating the Safety and Efficacy of Personalized Neoantigen Vaccine in Advanced Solid Tumors

iRECIST criteria (2017) to evaluate the anti-tumor activity of neoantigen tumor vaccine alone or in combination with PD-1

L-1β, IL-2, IL-6, IL-8, IL-10, TNF-α from time zero to time of last dose concentration

CD3+ 、CD3+∕CD4+ %、CD3+∕CD8+ %、CD4∕CD8 、CD3-∕CD19+ % from time zero to time of last dose concentration

Objective response rate (ORR: complete response \[CR\] + partial response \[PR\]), duration of response (DoR), best response rate (BOR), disease control rate (DCR: CR + PR + stable disease \[SD\]), progression-free survival (PFS), and overall survival (OS) based on RECIST 1.1.

NeoCura

Clinical Professor

Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

Pembrolizumab

In dose escalation phase, subject will only receive personalized neoantigen tumor vaccine. In dose expansion phase, subject will receive personalized neoantigen tumor vaccine combination with Pembrolizumab .

neoantigen tumor vaccine with or without Pembrolizumab In dose escalation phase, subjects will receive neoantigen tumor vaccine only. In dose expansion phase, subjects will receive neoantigen tumor vaccine combination with Pembrolizumab

Xinjing Wang

Baiyong Shen, M.D.&Ph.D

The main objective of this study was to observe and evaluate the safety and tolerability of mRNA-0217/S001 vaccine encoding personalized tumor neoantigens alone/in combination with Pembrolizumab injection for the treatment of Advanced Pancreatic Cancer. The secondary objective was to observe the preliminary efficacy of mRNA-0217/S001 personalized tumor vaccine in the treatment of advanced solid tumors with neoantigen-specific CD4+ and CD8+ T lymphocyte responses, objective tumor response rate (ORR) and disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) caused by mRNA-0217/S001 personalized tumor vaccine.

The traditional 3+3 design will be used in dose escalation

Personalized Tumor Vaccines and Pabolizumab in Patients With Advanced Pancreatic Cancer

Clinical Study of Personalized Tumor Vaccines mRNA-0217/S001 and Pabolizumab in Patients With Advanced Pancreatic Cancer

The highest dose of a drug or treatment that does not cause unacceptable side effects.

mRNA-0217/S001 personalized tumor vaccine induced neoantigen-specific CD4+ and CD8+ T lymphocyte responses

ORR calculates the ratio of the number of patients whose best response is complete remission (CR) or partial remission (PR) to the total number of evaluable patients according to RECIST 1.1 criteria. Those who have not been evaluated for lesion and tumor response will be regarded as non-evaluable patients and will not be counted.

DCR calculates the ratio of the number of patients whose best response is complete remission (CR), or partial remission (PR), or stable disease (SD) to the total number of evaluable patients according to RECIST 1.1 criteria. Those who have not been evaluated for lesion and tumor response will be regarded as non-evaluable patients and will not be counted.

During the trial conduction, all adverse events (including laboratory abnormality and clinical events) will be closely monitored, and all ≥ grade 3 adverse events per CTCAE (v 5.0) will be recorded, including but not limited to the toxicities potentially suspected to relate to injection procedures and/or mRNA Tumor Vaccine therapy as listed below:

Local erythema at the injection site, local allergic reactions at the injection site, fatigue, fever, chills, flu-like manifestations, vomiting, centrocytopenia, other unexpected adverse events

Progression-free Survival of Personalized mRNA Tumor Vaccine

Overall Survival of Personalized mRNA Tumor Vaccine

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety and Efficacy of Personalized Neoantigen Vaccine in Advanced Solid Tumors	NCT05359354	Solid Tumor	Personalized ne...	18 Years - 75 Years	Peking Union Medical College Hospital
Personalized Tumor Vaccines and Pabolizumab in Patients With Advanced Pancreatic Cancer	NCT05916261	Advanced Pancre...	Personalized ne...	18 Years -	Ruijin Hospital
Safety and Efficacy of Personalized Neoantigen Vaccine in Advanced Solid Tumors	NCT05359354	Solid Tumor	Personalized ne...	18 Years - 75 Years	Peking Union Medical College Hospital

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