T3011 + Pembrolizumab for Solid Cancers

Recruiting at 7 trial locations

Overseen By ImmVira Pharma Co. Ltd.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: ImmVira Pharma Co. Ltd

Must not be taking: HSV drugs, Live vaccines

Disqualifiers: Immunodeficiency, Autoimmune disease, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of two treatments, T3011 (an experimental treatment) and pembrolizumab (an immunotherapy drug), for individuals with advanced or spreading solid tumors. Some participants will receive only T3011, while others will receive both T3011 and pembrolizumab. This trial suits those with specific cancers, such as melanoma or non-small cell lung cancer, whose disease has worsened after standard treatments. Participants must have at least one tumor that can be injected with T3011. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must have stopped any previous anticancer therapy at least 21 days before starting the trial treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that T3011, both alone and combined with pembrolizumab, is generally safe and well-tolerated. A recent study found no serious side effects from these treatments. Patients with melanoma and other solid tumors tolerated T3011 well, whether used alone or with pembrolizumab. The combination therapy has demonstrated similar safety results, with no unexpected side effects reported.

Pembrolizumab, already approved by the FDA for various cancers, enhances the safety profile. Its use with T3011 has not raised any new safety concerns. While T3011 remains under study, early safety data is promising and suggests it is well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about T3011 and pembrolizumab for treating solid cancers because of their innovative approach. Pembrolizumab, already known as a powerful immunotherapy, works by blocking PD-1, a protein on immune cells that cancer uses to hide. T3011 introduces a new mechanism by using an oncolytic virus to directly target and kill cancer cells, while also boosting the immune system's response. This combination could potentially offer a more robust attack on tumors compared to standard treatments like chemotherapy or surgery, which often focus on directly removing or killing cancer cells rather than empowering the immune system. This dual-action strategy is what makes T3011 combined with pembrolizumab particularly promising.

What evidence suggests that this trial's treatments could be effective for solid cancers?

Research has shown that T3011, when injected directly into tumors, produces positive results in patients with advanced melanoma. On average, patients experienced about 12.9 months without cancer progression, meaning many did not see their cancer worsen for over a year. In this trial, some participants will receive T3011 alone, while others will receive it in combination with pembrolizumab, a well-known cancer drug. Early studies found this combination to be safe and effective. Participants who initially received T3011 alone and then switched to the combination after cancer progression demonstrated promising improvements. This suggests that the combination therapy might be beneficial when T3011 alone is insufficient. These findings offer hope for more effective treatment of solid tumors. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

Adults with advanced solid tumors who've had disease progression after standard treatments or are unlikely to benefit from them. They must have a tumor lesion suitable for injection, a life expectancy over 12 weeks, and agree to use contraception. Exclusions include pregnancy, certain allergies, active infections like COVID-19, recent vaccines, immunodeficiencies, organ transplants, some heart conditions.

Inclusion Criteria

I have a tumor that can be injected with treatment according to my doctor.

My organ functions are within normal ranges according to recent tests.

You have a disease that can be measured using a specific set of guidelines.

Exclusion Criteria

I do not have serious heart conditions like heart failure or unstable angina.

I am allergic to certain virus-based therapies or immune system drugs.

I am currently infected with COVID-19.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Dose Escalation

T3011 single agent dose escalation in participants with solid tumors using a 3+3 design to evaluate escalating doses

4 weeks

Phase 2a Part 1

Evaluation of safety, tolerability, and preliminary efficacy of T3011 as a single agent in various cohorts

Up to 2 years

Phase 2a Part 2

Evaluation of safety, tolerability, and preliminary efficacy of T3011 in combination with pembrolizumab

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year after last dose

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• T3011

Trial Overview The trial is testing T3011 alone and combined with pembrolizumab in patients with various advanced cancers. It's an early-phase study assessing safety and initial effectiveness of these treatments administered directly into the tumor (T3011) and intravenously (pembrolizumab).

How Is the Trial Designed?

Group I: Rollover Arm Experimental Treatment 1 Intervention

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

Group II: Phase 2a Part 2 Arm C Experimental Treatment 1 Intervention

RP2D T3011 + pembrolizumab in participants with NSCLC

Group III: Phase 2a Part 1 Arm B Experimental Treatment 1 Intervention

RP2D T3011 single agent in participants with other solid tumors

Group IV: Phase 2a Part 1 Arm A Experimental Treatment 1 Intervention

RP2D T3011 single agent in participants with melanoma

Group V: Phase 1 Experimental Treatment 1 Intervention

T3011 single agent dose escalation in participants with solid tumors

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

ImmVira Pharma Co. Ltd

Lead Sponsor

Trials

6

Recruited

530+

Published Research Related to This Trial

In a study involving 351 patients with advanced noncolorectal MSI-H/dMMR solid tumors, pembrolizumab showed a significant objective response rate (ORR) of 30.8%, indicating its efficacy in this patient population.

The treatment demonstrated a long median duration of response of 47.5 months and manageable safety, with only 11.1% of patients experiencing severe (grade 3-4) treatment-related adverse events, supporting its use in heavily pretreated cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study. Maio, M., Ascierto, PA., Manzyuk, L., et al.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a study of 100 patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab, further stratification of PD-L1 tumor proportion score (TPS) beyond 50% did not significantly affect progression-free survival (PFS).

Smoking status was associated with improved PFS, while prior radiotherapy was linked to decreased PFS, indicating that these factors, along with performance status, may serve as important biomarkers for predicting response to pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. Mander, ES., Merrick, CB., Nicholson, HA., et al.[2023]

Nivolumab and pembrolizumab are FDA-approved monoclonal antibodies that target PD-1, helping to enhance T cell activity against cancer by blocking the PD-1/PD-L1 interaction, which allows cancer cells to escape immune detection.

Both drugs have shown efficacy across multiple cancer types, including melanoma and non-small cell lung cancer, and are considered interchangeable options for treating these conditions, which may help manage the rising costs of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Prasad, V., Kaestner, V.[2022]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In a phase Ib trial involving 26 patients with advanced PD-L1-positive ovarian cancer, pembrolizumab demonstrated a confirmed objective response rate of 11.5%, indicating some level of antitumor activity, with 1 complete response and 2 partial responses observed.

The treatment was generally well-tolerated, with 73.1% of patients experiencing treatment-related adverse events, but no deaths or treatment discontinuations due to these events, suggesting that pembrolizumab has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Varga, A., Piha-Paul, S., Ott, PA., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04370587?term=AREA%5BBasicSearch%5D(t3011)&rank=2

NCT04370587 | A Clinical Study of Intratumoral MVR- ... 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 ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.9535

Updated results from an ongoing phase 1/2a study of ... Conclusions: Both T3011 IT monotherapy and combination therapy with pembrolizumab were safe and tolerable. The efficacy of T3011 in immune- ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05602792

NCT05602792 | A Study of T3011 Administered Via ... This is a Phase I/IIa, open-label, first-in-human study of T3011 given via intratumoral (IT) injection in participants with advanced or metastatic solid ...

4. clin.larvol.com clin.larvol.com/trial-detail/NCT05602792

A Study of T3011 Administered Via Intratumoral Injection in ... | "Following the recent publication of efficacy data on advanced melanoma, ImmVira's intratumoral injected OV product MVR-T3011 IT has also shown positive ...

5. prnewswire.com prnewswire.com/news-releases/immvira-clinical-snapshot-intratumoral-injected-ov-mvr-t3011-it-monotherapy-achieved-median-pfs-of-12-9-months-on-treatment-of-melanoma-301742055.html

ImmVira Clinical Snapshot: Intratumoral Injected OV (MVR ... PRNewswire/ -- ImmVira's first intratumoral injected OV product MVR-T3011 IT has shown positive efficacy in the course of clinical studies ...

6. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.9535

Melanoma/Skin Cancers Conclusions: Both T3011 IT monotherapy and combination therapy with pembrolizumab were safe and tolerable. The efficacy of T3011 in immune- ...

7. trials.braintumor.org trials.braintumor.org/trials/NCT04370587

A Clinical Study of Intratumoral MVR-T3011 (T3011) Given as ... 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 ...

8. clin.larvol.com clin.larvol.com/trial-detail/NCT04780217

Intravenous T3011 Given as a Single Agent and in ... PRNewswire 2022 - ImmVira's MVR-T3011 IV completed first 2 cohorts dose-escalation of U.S. Phase I clinical study with favorable safety data. P1/2, N=78; ...