Description:
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.
Title
- Brief Title: 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
- 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
Clinical Trial IDs
- ORG STUDY ID:
CTIV1708
- NCT ID:
NCT04370587
Conditions
Interventions
Drug | Synonyms | Arms |
---|
T3011 | | Phase 1 |
Purpose
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.
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Phase 1 | Experimental | T3011 single agent dose escalation in participants with solid tumors | |
Phase 2a Part 1 Arm A | Experimental | RP2D T3011 single agent in participants with melanoma | |
Phase 2a Part 1 Arm B | Experimental | RP2D T3011 single agent in participants with other solid tumors | |
Phase 2a Part 2 | Experimental | RP2D T3011 + pembrolizumab in participants with NSCLC | |
Rollover Arm | Experimental | RP2D T3011 + pembrolizumab in participants who have progressed on T3011 single agent | |
Eligibility Criteria
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Safety and tolerability of escalating doses T3011 |
Time Frame: | Up to 2 years from first dose of T3011 |
Safety Issue: | |
Description: | Number of participants in dose escalating cohorts with dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities. |
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 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 assessments by 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 after last dose of T3011 |
Safety Issue: | |
Description: | OS is defined as the time from enrollment to death from any cause. |
Measure: | Presence of neutralizing antibodies of anti-PD-1 antibody for antidrug antibodies (ADAs) development |
Time Frame: | Up to 2 years from first dose of T3011 |
Safety Issue: | |
Description: | To evaluate the immunogenicity of anti-PD-1 antibody expressed by T3011 given as single agent and in combination with pembrolizumab post injection. |
Measure: | Presence and frequency of T3011 in injection site swab, saliva, and urine |
Time Frame: | Up to 2 years from first dose of T3011 |
Safety Issue: | |
Description: | To evaluate the virus shedding of T3011 following intratumoral injection |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | ImmVira Pharma Co. Ltd |
Last Updated
June 25, 2021