Description:
This is a Phase 1/2a open label study to evaluate the safety and preliminary efficacy of
intravenous T3011 given alone and in combination with intravenous pembrolizumab in
participants with advanced or metastatic solid tumors.
Title
- Brief Title: A Clinical Study of Intravenous T3011 Given as a Single Agent and in Combination With Intravenous Pembrolizumab in Participants With Advanced or Metastatic Solid Tumors
- Official Title: A Phase 1/2a Open-Label Dose Escalation and Dose Expansion Study of T3011 When Administered Via Intravenous Infusion as a Single Agent and in Combination With Pembrolizumab in Participants With Advanced or Metastatic Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
MVR-T3011-003
- NCT ID:
NCT04780217
Conditions
- Metastasis in Lung
- Metastasis in Liver
- Solid Tumor
- NSCLC
Interventions
Drug | Synonyms | Arms |
---|
T3011 | | Phase 1 Part A |
Purpose
This is a Phase 1/2a open label study to evaluate the safety and preliminary efficacy of
intravenous T3011 given alone and in combination with intravenous pembrolizumab in
participants with advanced or metastatic solid tumors.
Detailed Description
This is a Phase 1/2a, open-label, first-in-human study of T3011 given via intravenous (IV)
infusion as a single agent and in combination with IV pembrolizumab in participants with
advanced or metastatic solid tumors. The Phase 1 Part A 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 IV T3011 RP is established, the Phase 1 Part B
part of the study will begin. Phase 1 Part B is IV T3011 in combination with IV pembrolizumab
dose escalation which will use a 3+3 design to evaluate escalating doses of IV T3011 in
combination with IV pembrolizumab. Total enrollment will depend on the toxicities and/or
activity observed, with approximately 18 evaluable participants enrolled. Upon completion of
Phase 1 Part B, Phase 2a will begin. The safety, tolerability, and preliminary efficacy of IV
T3011 given in combination with IV pembrolizumab will be evaluated in 15 participants with
histologically or pathologically confirmed metastatic NSCLC (Arm A) and 15 participants with
advanced solid tumors with metastasis in either the liver and/or lung (Arm B).
Trial Arms
Name | Type | Description | Interventions |
---|
Phase 1 Part A | Experimental | T3011 Single Agent Dose Escalation in participants with solid tumors | |
Phase 1 Part B | Experimental | Dose Escalation of Combination T3011 + pembrolizumab in participants with solid tumors | |
Phase 2a Arm A | Experimental | RP2D T3011 + pembrolizumab in participants with NSCLC | |
Phase 2a Arm B | Experimental | RP2D T3011 + pembrolizumab in participants with advanced solid tumors with metastasis in either liver and/or lung | |
Eligibility Criteria
Inclusion Criteria:
1. Participants with one of the following cancers:
- Pathologically confirmed, locally recurrent or metastatic solid tumors
- Histologically or cytologically confirmed NSCLC that is recurrent or metastatic
- Histologically or cytologically diagnosed advanced solid tumors with metastasis
in liver and/or lung
2. Disease progression after SOC therapy or in the opinion of the Investigator unlikely
to benefit from SOC therapy.
3. Age 18 years or older.
4. Measurable disease per RECIST version 1.1.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1.
6. Life expectancy > 12 weeks.
7. Demonstrate adequate organ function as defined by acceptable laboratory testing
results.
8. 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
C1D1.
9. Last dose of previous anticancer therapy ≥ 21 days, radiotherapy > 21 days, or
surgical intervention > 21 days prior to the first dose of T3011.
10. Recovered from all prior anticancer therapy toxicities.
11. Willingness to provide fresh tumor biopsy specimens as specified in the Schedule of
Assessments.
12. Capable of understanding and complying with protocol requirements.
13. Signed and dated institutional review board/independent ethics committee (IRB/IEC)
approved informed consent form (ICF) before any protocol-directed screening procedures
are performed.
Exclusion Criteria:
1. Prior treatment with another oncolytic virus or cellular therapy.
2. Previous unacceptable intolerance to anti-PD-1 monoclonal antibody.
3. Requires continued concurrent systemic therapy with any drug active against HSV.
4. Live vaccines within 4 weeks of initiation of study treatment.
5. Primary or acquired immunodeficient states.
6. Pregnant or lactating.
7. Splenectomy, previous allogenic tissue/solid organ transplant.
8. Active hepatitis B virus, hepatitis C virus, or a positive serological test at
Screening.
9. Active autoimmune disease or medical conditions requiring chronic steroid.
10. Untreated and/or symptomatic metastatic central nervous system (CNS) disease.
11. History of seizure disorders within 6 months of Screening.
12. Active oral or skin herpes lesion at Screening.
13. Congestive heart failure, active coronary artery disease, unevaluated new onset angina
within 3 months or unstable angina, or clinically significant cardiac arrhythmias.
14. 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.
15. Known or suspected active infection with SARS-CoV-2 virus.
16. 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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | To evaluate the safety and tolerability of escalating doses of single agent IV T3011 (Part A) and of IV T3011 in combination with pembrolizumab (Part B). |
Time Frame: | Up to 2 years from first dose of T3011 |
Safety Issue: | |
Description: | Incidence and characteristics of TEAEs |
Secondary Outcome Measures
Measure: | Overall response rate (ORR) |
Time Frame: | Up to 2 years from first dose of T3011 |
Safety Issue: | |
Description: | ORR is defined as the proportion of participants who have a partial response (PR) or complete response (CR) to intervention, based on investigator assessments by RECIST v1.1 and iRECIST. |
Measure: | Disease control rate (DCR) |
Time Frame: | Up to 2 years from first dose of T3011 |
Safety Issue: | |
Description: | DCR is defined as the percentage of participants who have achieved CR, PR, or stable disease (SD) based on investigator assessments per RECIST v1.1 and iRECIST. |
Measure: | Duration of response (DOR) |
Time Frame: | Up to 2 years from first dose of T3011 |
Safety Issue: | |
Description: | 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. |
Measure: | Durable response (DR) |
Time Frame: | Up to 2 years from first dose of T3011 |
Safety Issue: | |
Description: | DR is defined as objective response (CR or PR) according to RECIST v1.1 and iRECIST. |
Measure: | Progression-free survival (PFS) |
Time Frame: | Up to 2 years from first dose of T3011 |
Safety Issue: | |
Description: | 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. |
Measure: | Overall survival (OS) |
Time Frame: | Up to 1 year from last dose of T3011 |
Safety Issue: | |
Description: | OS is defined as the time from enrollment to death from any cause. |
Measure: | Quantitative viral DNA level of T3011 in urine and saliva. |
Time Frame: | Up to 2 years from first dose of T3011 |
Safety Issue: | |
Description: | To evaluate viral shedding in participants dosed with IV T3011. |
Measure: | Quantitative measurements of blood viral DNA level, serum IL-12 and anti-PD-1 antibody concentration. |
Time Frame: | Up to 2 years from first dose of T3011 |
Safety Issue: | |
Description: | To evaluate the pharmacokinetic (PK) in participants dosed with IV T3011. |
Measure: | Presence of anti-herpes simplex virus type 1 (HSV-1) immunoglobulin G (IgG) and anti-PD-1 idiotypic antibody. |
Time Frame: | Up to 2 years from first dose of T3011 |
Safety Issue: | |
Description: | To evaluate the immunogenicity in participants dosed with IV T3011. |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | ImmVira Pharma Co. Ltd |
Last Updated
August 27, 2021