A Study of T3011 Administered Via Intravenously in Patients With Advanced Solid Tumors.

A Phase I/IIa Study to Assess the Safety, Tolerability, Biodistribution and Pharmacodynamic of T3011 Herpes Virus Administered Via Intravenously in Patients With Advanced Solid Tumors.

This is a multicenter, open-label study conducted in 3 phases:

Dose escalation stage: The stage contain 4 cohorts, each cohort divided into 2 groups （group A, single dose and Group B, multiple dose）.Dose escalation will use a 3+3 design to evaluate escalating doses of T3011.Cohorts of three subjects will be enrolled at each T3011 dose level with expansion to six subjects, if necessary, to assess toxicity. Total enrollment will depend on the toxicities observed, with approximately 4-24 evaluable subjects enrolled in dose escalation stage.

Dose extension stage: The SMC will evaluate the available safety and preliminary efficacy data and initiate dose-expansion studies for the appropriate indications Phase IIa: To explore the safety of intravenous administration and expand the study in other indications. the stage will be carried out gradually based on the data obtained from the phase I study.

Study Overview

• Status: Recruiting
• Conditions: Lymphoma; Lung Cancer; Advanced Solid Tumor; Liver Cancer; Mesothelioma of Pleura
• Intervention / Treatment: Biological: T3011

Detailed Description

This is a multicenter, open-label study conducted in 3 phases:

Dose escalation stage: The stage contains 4 cohorts, divided into cohort 1 (1x106PFU/ dose), cohort 2 (1x107PFU/ dose), cohort 3 (1x108PFU/ dose) and cohort 4 (3x108PFU/ dose). Each cohort divided into 2 groups （group A, single dose and Group B, multiple dose）.Dose escalation will use a 3+3 design to evaluate escalating doses of T3011. At any dose level, if no DLT occurs among the first 3 subjects, then escalation to the next dose level may proceed, with the approval of the SMC. If 1 DLT occurs in the first 1 to 3 subjects, the dose level will expand to a maximum of 6 subjects. If no DLT occurs among the additional subjects, then escalation to the next dose level may proceed, with the approval of the SMC. If 2 or more DLTs occur within a cohort, then that dose level will be above the maximum tolerated dose (MTD) (the highest dose where no more than 1 of 6 subjects has experienced a DLT), and new subjects will be enrolled at the previous lower (tolerated) dose level until that cohort has 6 subjects. This lower dose level will be considered the MTD if ≤ 1 in 6 subjects has a DLT. At the end of dose escalation, the SMC will recommend a dose (the recommended phase 2 dose [RP2D]) of T3011 to be used in phase 2a expansion study based upon MTD identification, cumulative safety, pharmacokinetic (PK), efficacy, and pharmacodynamic data. Total enrollment will depend on the toxicities observed, with approximately 4-24 evaluable subjects enrolled in dose escalation stage.

In group A, participant will receive a single dose and the DLT evaluation period is 14 days.

In group B, Participants will receive administration at D1/D4/D8 of every cycle. The DLT evaluation period will be the first 21-day Cycle in group B. Tumor evaluation was performed every two cycles. The maximum treatment period should not exceed 4 cycles. Group B of cohort X was enrolled only after the DLT assessed for group A of cohort X and SMC approval to proceed to the next cohort assessment.

Dose extension stage: The SMC will evaluate the available safety and preliminary efficacy data and initiate dose-expansion studies for the appropriate indications Phase IIa: To explore the safety of intravenous administration and expand the study in other indications. the stage will be carried out gradually based on the data obtained from the phase I study.

• Study Type: Interventional
• Enrollment (Anticipated): 74
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 101149
    • Recruiting
    • Beijing Chest Hospital
    • Contact: Hu Ying, M.D.; Phone Number: 010-89509000; Email: clinicaltrials@immviragroup.com
  • Shanghai, China, 200030
    • Recruiting
    • Shanghai Chest Hosptial
    • Contact: Lu Shun, Professor; Phone Number: 12345 86-021-22200000; Email: clinicaltrials@immviragroup.com
  • Anhui
    • Bengbu, Anhui, China, 233099
      • Recruiting
      • The First Affiliated Hospital of Bengbu Medicial College
      • Contact: Wang Junbin, Professor; Phone Number: 055-3086120; Email: clinicaltrials@immviragroup.com
  • Guangdong
    • Guanzhou, Guangdong, China, 510280
      • Recruiting
      • Zhujiang Hospital of Southern Medical University
      • Contact: Zhang Jian, Professor; Phone Number: 020-61643888; Email: clinicaltrials@immviragroup.com
  • Henan
    • Luoyang, Henan, China, 450052
      • Recruiting
      • The First Affiliated Hospital of Henan University of Science and Technology
      • Contact: Zhang Zhiye, Professor; Phone Number: 0379-69823015; Email: clinicaltrials@immviragroup.com
    • Zhengzhou, Henan, China, 450003
      • Recruiting
      • Henan Cancer Hosptial
      • Contact: Luo Suxia, M.D.; Phone Number: 400-0371818; Email: clinicaltrials@immviragroup.com
  • Sichuan
    • Chengdu, Sichuan, China, 610044
      • Recruiting
      • West China Hospital of Sichuan University
      • Contact: Zhang Shuang, professor; Phone Number: 028-85422114; Email: clinicaltrials@immviragroup.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. Locally recurrent or metastatic solid tumors, There is currently no effective treatment (including treatment intolerance).

  2. Age 18 years or older. 3. At least one target lesion per RECIST version 1.1. 4. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1. 5. Life expectancy ≥ 12 weeks. 6. Women of childbearing potential must have a negative serum pregnancy test at Screening within 7 days of dosing with T3011.

  7. Understand and sign ICF voluntarily,capable of understanding and complying with protocol requirements.

Exclusion Criteria:

• 1. Pregnant or lactating or plan to pregnant or give birth during the trial. 2. Splenectomy, previous allogenic organ transplant. 3. Prior treatment with another gene therapy（except T3011）. 4. Requires continued concurrent systemic therapy with any drug active against HSV (acyclovir, valaciclovir, penciclovir, famciclovir, ganciclovir, foscarnet, cidofovir). Topical use of drugs against HSV are allowed.

  5. History of allergic reactions attributed to compounds of similar biological composition to HSV-1, IL-12, or anti-PD-1 monoclonal antibody or their excipients.

  6. Prior treatment with anti-PD-(L)1 monoclonal antibody in combination with IL-12.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: T3011 Herpes Virus Injection	Biological: T3011; T3011 will be administered through IV drip

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the safety and tolerability of escalating doses of IV T3011 in Patients with advanced malignant tumors	Incidence of AE(TEAE)	Up to 2 years from first dose of T3011
Assess DLTs and identify the RP2D of single agent IV T3011	Incidence of DLT	Up to 2 years from first dose of T3011
Assess safety and tolerability of T3011 intravenous administration at MTD or RP2D doses through dose extension study	Incidence of AE(TEAE)	Up to 2 years from first dose of T3011

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the biodistribution and viral shedding of IV T3011	Measurement of T3011 in subjects' blood, urine, and saliva for biodistribution and viral shedding	Up to 2 years from first dose of T3011
Evaluate the immunogenicity of IV T3011	Measurement of ADAs and Nabs of IL-12, anti-PD-1 antibody and HSV-1 (test Nabs when ADAs are positive).	Up to 2 years from first dose of T3011
Evaluate the preliminary clinical response of single agent IV T3011	ORR PFS and OS	Up to 2 years from first dose of T3011

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploring tumor immunomodulatory mechanism	Lymphocyte typing	Up to 42 days from first dose of T3011
Exploring histological changes after IT T3011	Immunofluorescence detection	Up to 42 days from first dose of T3011
Exploring the relationship between genetic changes and drug efficacy	Tumor tissue sequencing	Up to 42 days from first dose of T3011

Collaborators and Investigators

• Sponsor: ImmVira Pharma Co. Ltd

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2022
• Primary Completion (ANTICIPATED): June 1, 2024
• Study Completion (ANTICIPATED): December 1, 2024

Study Registration Dates

• First Submitted: October 18, 2022
• First Submitted That Met QC Criteria: October 24, 2022
• First Posted (ACTUAL): October 28, 2022

Study Record Updates

• Last Update Posted (ACTUAL): October 28, 2022
• Last Update Submitted That Met QC Criteria: October 24, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Dose escalation; Advanced solid tumor; Oncolytic virus; Herpes virus; T3011
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Adenoma; Neoplasms, Mesothelial; Mesothelioma
• Other Study ID Numbers: MVR-T3011-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No