A Clinical Study of Intratumoral MVR-T3011 (T3011) Given as a Single Agent and in Combination With Intravenous Pembrolizumab in Participants With Advanced or Metastatic Solid Tumors

Sponsor
ImmVira Pharma Co. Ltd (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04370587
Collaborator
(none)
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Study Details

Study Description

Brief Summary

This is a Phase 1/2a, open-label, study to evaluate the safety and preliminary efficacy of intratumoral T3011 given alone and in combination with intravenous pembrolizumab in participants with advanced or metastatic solid tumors.

Condition or Disease Intervention/Treatment Phase
  • Biological: T3011
  • Combination Product: T3011 + pembrolizumab
Phase 1/Phase 2

Detailed Description

This is a Phase 1/2a, open-label, first-in-human study of T3011 given via intratumoral (IT) injection as a single agent and in combination with IV pembrolizumab in participants with advanced or metastatic solid tumors. The Phase 1 portion of the study is a single agent dose escalation which will use a 3+3 design to evaluate escalating doses of T3011. Total enrollment will depend on the toxicities and/or activity observed, with approximately 24 evaluable participants enrolled. Once the RP2D is established Phase 2a Part 1 will enroll approximately 10 participants with locally recurrent or metastatic melanoma (Arm A) and approximately 10 participants with advanced or metastatic solid tumors, excluding metastatic melanoma (Arm B). During Phase 2a Part 1 the safety, tolerability, and preliminary efficacy of T3011 as a single agent will be evaluated. Upon completion of Phase 2a Part 1, Phase 2a Part 2 will begin. The safety, tolerability, and preliminary efficacy of IT T3011 given in combination with IV pembrolizumab will be evaluated in 20 participants with histologically or pathologically confirmed metastatic NSCLC. A rollover arm is also included in this study to allow participants who have documented progression on T3011 alone to receive T3011 in combination with pembrolizumab if considered eligible.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
64 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2a, Open-Label, Dose Escalation and Expansion Study of the Safety and Tolerability of T3011 When Administered Via Intratumoral Injection as a Single Agent and in Combination With Intravenous Pembrolizumab in Participants With Advanced or Metastatic Solid Tumors
Actual Study Start Date :
Sep 17, 2020
Anticipated Primary Completion Date :
Oct 31, 2022
Anticipated Study Completion Date :
Oct 31, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Phase 1

T3011 single agent dose escalation in participants with solid tumors

Biological: T3011
T3011 will be administered up to 4mL as an intratumoral injection given Q2W.

Experimental: Phase 2a Part 1 Arm A

RP2D T3011 single agent in participants with melanoma

Biological: T3011
T3011 will be administered up to 4mL as an intratumoral injection given Q2W.

Experimental: Phase 2a Part 1 Arm B

RP2D T3011 single agent in participants with other solid tumors

Biological: T3011
T3011 will be administered up to 4mL as an intratumoral injection given Q2W.

Experimental: Phase 2a Part 2

RP2D T3011 + pembrolizumab in participants with NSCLC

Combination Product: T3011 + pembrolizumab
T3011 will be administered up to 4mL as an intratumoral injection in combination with intravenous pembrolizumab given Q3W.

Experimental: Rollover Arm

RP2D T3011 + pembrolizumab in participants who have progressed on T3011 single agent

Combination Product: T3011 + pembrolizumab
T3011 will be administered up to 4mL as an intratumoral injection in combination with intravenous pembrolizumab given Q3W.

Outcome Measures

Primary Outcome Measures

  1. Safety and tolerability of escalating doses T3011 [Up to 2 years from first dose of T3011]

    Number of participants in dose escalating cohorts with dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.

  2. To determine the dose(s) of T3011 to be examined in Phase 2a [Through the first two T3011 injections (approximately 28 days)]

    Incidence of DLTs

  3. Safety and tolerability of T3011 dose(s) selected from Phase 1 in disease specific cohorts [Up to 2 years from first dose of T3011]

    Number of participants with treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.

  4. Characterize the safety and tolerability of T3011 in combination with pembrolizumab [Up to 2 years from first dose of T3011]

    Number of participants with treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.

  5. Characterize the safety and tolerability of T3011 in combination with pembrolizumab in participants who progress on T3011 alone [Up to 2 years from first dose of T3011]

    Number of participants with treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.

Secondary Outcome Measures

  1. Overall response rate (ORR) [Up to 2 years from first dose of T3011]

    ORR is defined as the proportion of participants who have a partial response (PR) or complete response (CR) to intervention, based on assessments by RECIST v1.1 and iRECIST.

  2. Disease control rate (DCR) [Up to 2 years from first dose of T3011]

    DCR is defined as the percentage of participants who have achieved CR, PR, or stable disease (SD) based on assessments by RECIST v1.1 and iRECIST.

  3. Duration of response (DOR) [Up to 2 years from first dose of T3011]

    DOR is defined as the time from the first met CR or PR until disease progression or death due to any cause, whichever occurs first.

  4. Durable response (DR) [Up to 2 years from first dose of T3011]

    DR is defined as objective response (CR or PR) according to RECIST v1.1 and iRECIST.

  5. Progression-free survival (PFS) [Up to 2 years from first dose of T3011]

    PFS is defined as the time from enrollment to the first documentation of progressive disease (PD) or death from any cause, whichever occurs first per RECIST v1.1 and iRECIST.

  6. Overall Survival (OS) [Up to 1 year after last dose of T3011]

    OS is defined as the time from enrollment to death from any cause.

  7. Presence of neutralizing antibodies of anti-PD-1 antibody for antidrug antibodies (ADAs) development [Up to 2 years from first dose of T3011]

    To evaluate the immunogenicity of anti-PD-1 antibody expressed by T3011 given as single agent and in combination with pembrolizumab post injection.

  8. Presence and frequency of T3011 in injection site swab, saliva, and urine [Up to 2 years from first dose of T3011]

    To evaluate the virus shedding of T3011 following intratumoral injection

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion Criteria:
  1. Age 18 years or older.

  2. Histologically or pathologically confirmed diagnosis of locally recurrent or metastatic advanced malignancy.

  3. Disease progression after standard of care (SOC) therapy or in the opinion of the Investigator unlikely to benefit from SOC therapy.

  4. Measurable disease per RECIST version 1.1.

  5. Must have at least 1 tumor lesion that is accessible for IT injection of T3011 in the opinion of the investigator.

  6. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

  7. Life expectancy > 12 weeks.

  8. Demonstrate adequate organ function as defined by acceptable laboratory testing results.

  9. Women of child-bearing potential (WCBP) and men must agree to use adequate contraception prior to study entry, while on study treatment, and for six months after receiving last dose of T3011. WCBP must have a negative serum pregnancy test prior to W1D1.

  10. Last dose of previous anticancer therapy ≥ 21 days, radiotherapy > 21 days, or surgical intervention > 21 days prior to the first dose of T3011.

  11. Recovered from all prior anticancer therapy toxicities.

  12. Willingness to provide fresh tumor biopsy specimens as specified in the Schedule of Assessments.

  13. Capable of understanding and complying with protocol requirements.

  14. Signed and dated institutional review board/independent ethics committee-approved informed consent form before any protocol-directed screening procedures are performed.

Key Exclusion Criteria:
  1. Have only tumors with severe fibrosis and therefore not injectable.

  2. Patients with injectable tumors impinging upon major airways or blood vessels.

  3. Prior treatment with another oncolytic virus or cellular therapy.

  4. Requires continued concurrent therapy with any drug active against HSV.

  5. Systemic therapy with immunosuppressive agents within 28 days before the start of T3011 treatment.

  6. Live vaccines within 4 weeks of initiation of study treatment.

  7. Primary or acquired immunodeficient states.

  8. Pregnant or lactating.

  9. Prior organ transplantation.

  10. Active hepatitis B virus, hepatitis C virus, and HIV infection or a positive serological test at Screening within 14 days of dosing with T3011.

  11. Active autoimmune disease or medical conditions requiring chronic steroid.

  12. History of or current central nervous system metastases.

  13. History of seizure disorders within 6 months of Screening.

  14. Active oral or skin herpes lesion at Screening.

  15. Active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis requiring treatment with systemic steroids.

  16. Congestive heart failure, active coronary artery disease, unevaluated new onset angina within 3 months or unstable angina, or clinically significant cardiac arrhythmias.

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

  18. Active infection with SARS-CoV-2 virus.

  19. Other systemic conditions or organ abnormalities that, in the opinion of the investigator, may interfere with the conduct and/or interpretation of the current study.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Banner MD Anderson Cancer Center Gilbert Arizona United States 85234
2 Massachusetts General Hospital Boston Massachusetts United States 02114
3 Dana Farber Cancer Institute Boston Massachusetts United States 02215
4 University of Pittsburgh Medical Center Pittsburgh Pennsylvania United States 15232
5 Mary Crowley Cancer Research Dallas Texas United States 75230
6 Southern Oncology Bedford Park Australia
7 Peninsula & South Eastern Haematology and Oncology Group Frankston Australia
8 The Alfred Melbourne Australia

Sponsors and Collaborators

  • ImmVira Pharma Co. Ltd

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
ImmVira Pharma Co. Ltd
ClinicalTrials.gov Identifier:
NCT04370587
Other Study ID Numbers:
  • CTIV1708
First Posted:
May 1, 2020
Last Update Posted:
Jun 25, 2021
Last Verified:
Jun 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jun 25, 2021