Treatment of advanced solid tumors with T3011 and pembrolizumab

A Phase 1/2a, Open-Label, Dose Escalation and Expansion Study of the Safety and Tolerability of T3011 Administered Via Intratumoral Injection as a Single Agent and in Combination With Intravenous Pembrolizumab in Patients With Advanced or Metastatic Solid Tumors

This study is testing a new treatment called T3011, given as an injection, alone and with another drug called pembrolizumab, to see if it helps people with advanced solid tumors like melanoma and head and neck cancer.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: ImmVira Pharma Co. Ltd (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, pembrolizumab
• Locations: 9 sites (Gilbert, Arizona and 8 other locations)
• Trial ID: NCT04370587 on ClinicalTrials.gov

What this trial studies

This Phase 1/2a clinical study evaluates the safety and preliminary efficacy of T3011, administered via intratumoral injection, both as a single agent and in combination with intravenous pembrolizumab in patients with advanced or metastatic solid tumors. The study begins with a dose escalation phase to determine the recommended phase 2 dose (RP2D) of T3011, followed by a multi-arm evaluation of its efficacy in specific cancer types including melanoma, head and neck squamous cell carcinoma (HNSCC), sarcoma, and cutaneous squamous cell carcinoma (cSCC). Participants who have shown disease progression on T3011 alone may have the option to receive the combination treatment. The study aims to gather data on safety, tolerability, and preliminary efficacy across different cancer types.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with advanced or metastatic solid tumors who have progressed after standard therapies.

Not a fit: Patients with early-stage tumors or those who have not yet undergone standard of care therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors who have limited treatment options.

How similar studies have performed: Other studies have shown promising results with similar immunotherapy approaches, suggesting potential for success in this novel combination treatment.

Eligibility criteria

Key Inclusion Criteria:

1. Age 18 years or older.
2. Disease progression after standard of care (SOC) therapy or in the opinion of
3. The Investigator unlikely to benefit from SOC therapy. Inclusion Diagnosis Phase 1 - Histologically or pathologically confirmed locally recurrent or metastatic advanced malignancy.

   Phase 2a Part 1 i. Arm A - locally recurrent or metastatic melanoma. Participants must have received no more than 3 prior regimens for advanced or metastatic disease.

   ii. Arm B - locally recurrent or metastatic HNSCC. It must also meet the following criteria: 1) Disease progression to platinum-containing chemotherapy; 2) Failure to anti-PD-1/PDL1 blockade after receiving at least 2 doses alone or in combination.

   iii. Arm C - Sarcoma. Participants must have received no more than three lines of prior anti-cancer therapies.

   iv. Arm D - locally recurrent or metastatic cSCC. Participants must have received no more than 3 prior regimens for advanced or metastatic disease.

   Phase 2a Part 2 i.v. Arm E - Histologically or pathologically confirmed NSCLC that is advanced or recurrent, without EGFR mutation or ALK rearrangement. Participants must have received at least one line but no more than three lines of prior anti-cancer therapies.
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 uninjectable tumors..
2. Patients with injectable tumors impinging upon major airways or blood vessels.
3. HNSCC only: Prior re-irradiation field containing carotid artery.
4. Greater than 3 distant metastatic lymph node regions and/or metastatic lesions or the largest distant metastases with a diameter of more than 3 cm (non-sarcoma)/5 cm (sarcoma) unless the lesion is to be injected.
5. Prior treatment with another OV (including T-VEC), tumor vaccines, cellular therapy or gene therapy.
6. Prior intolerance to anti-PD-(L)1 monoclonal antibody or history of immunotherapy related non-infectious pneumonitis/interstitial lung disease.
7. Prior treatment with anti-PD-(L)1 monoclonal antibody in combination with IL-12.
8. Requires continued concurrent therapy with any drug active against HSV.
9. Live vaccines, attenuated vaccines within 4 weeks prior to initiation of study treatment (participants vaccinated with inactivated vaccines can be enrolled.
10. Primary or acquired immunodeficient states.
11. Pregnant or lactating.
12. Prior organ transplantation.
13. Active hepatitis B virus, hepatitis C virus, and HIV infection or a positive serological test at Screening within 14 days of dosing with T3011.
14. Active autoimmune disease or medical conditions requiring chronic steroid or immunosuppressive therapy within 4 weeks prior to first administration of study treatment.
15. History of or current central nervous system metastases.
16. History of seizure disorders within 6 months of Screening.
17. Active oral or skin herpes lesion at Screening.
18. Active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis requiring treatment with systemic steroids.
19. Congestive heart failure, active coronary artery disease, unevaluated new onset angina within 3 months or unstable angina, or clinically significant cardiac arrhythmias.
20. 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. 21. Participants with moderate to large amount of pleural effusion, ascites or pericardial effusion who need drug or medical intervention.

22\. 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.

Where this trial is running

Gilbert, Arizona and 8 other locations

• Banner MD Anderson Cancer Center — Gilbert, Arizona, United States (Completed)
• Massachusetts General Hospital — Boston, Massachusetts, United States (Recruiting)
• Dana Farber Cancer Institute — Boston, Massachusetts, United States (Recruiting)
• University of Pittsburgh Medical Center — Pittsburgh, Pennsylvania, United States (Recruiting)
• Mary Crowley Cancer Research — Dallas, Texas, United States (Recruiting)
• Virginia Cancer Specialists — Fairfax, Virginia, United States (Recruiting)
• Southern Oncology — Bedford Park, Australia (Recruiting)
• Peninsula & South Eastern Haematology and Oncology Group — Frankston, Australia (Recruiting)
• The Alfred — Melbourne, Australia (Recruiting)

Study contacts

• Study coordinator: ImmVira Pharma Co. Ltd.

Conditions Solid Tumor; Melanoma; HNSCC; Sarcoma; Squamous Cell Carcinoma; NSCLC