T3011 + Pembrolizumab for Advanced Cancers

Recruiting at 5 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: Antivirals, Steroids

Disqualifiers: Immunodeficiency, Active infection, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called T3011, both alone and combined with pembrolizumab, to evaluate its effectiveness for people with advanced solid tumors such as lung, liver, or ovarian cancer. The study will explore different doses to determine the most effective and safe level. Suitable candidates have solid tumors that have returned or spread and have not responded well to standard treatments like chemotherapy. 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 it.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot continue systemic therapy with drugs active against HSV, and you should not have had live vaccines within 4 weeks before starting the study treatment.

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

Research has shown that T3011, whether used alone or with pembrolizumab, has promising safety results. In earlier studies, researchers tested T3011 in people with advanced tumors and found it to be generally safe and well-tolerated. Most side effects were mild or moderate, indicating they weren't too serious.

In the study combining T3011 with pembrolizumab, the safety results were also positive. The combination proved safe for participants, with no unexpected side effects. Many people participated in these studies, and the consistent safety results indicate reliable findings.

These results are encouraging for those considering joining a trial with T3011, either by itself or with pembrolizumab. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about T3011 and its combination with pembrolizumab for advanced cancers because they offer a fresh approach to tackling solid tumors. Unlike traditional therapies that might rely solely on chemotherapy, T3011 is an oncolytic virus designed to selectively infect and destroy cancer cells, sparing healthy cells. This unique mechanism not only triggers direct tumor destruction but also stimulates the immune system to attack cancer cells, potentially enhancing the effects of pembrolizumab, an immune checkpoint inhibitor. This dual-action strategy could improve treatment responses and offer new hope for those with challenging cancer types.

What evidence suggests that T3011 + pembrolizumab could be effective for advanced cancers?

Research suggests that T3011 could help treat advanced cancers. In studies, T3011 showed promising results in patients with melanoma unresponsive to other treatments. It seems to alter the tumor environment, potentially aiding the body in fighting cancer more effectively. In this trial, some participants will receive T3011 alone. When combined with pembrolizumab, T3011 may enhance the immune system's ability to locate and destroy cancer cells. Although more research is needed, early signs offer hope for people with advanced solid tumors. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

Adults with advanced solid tumors, including specific cancers like NSCLC and colorectal cancer, who have not responded to standard treatments. Participants must be in good health otherwise, with proper organ function and no severe immune deficiencies or active infections. Women of childbearing potential must use effective contraception.

Inclusion Criteria

Life expectancy ≥ 12 weeks

I understand and can follow the study's requirements.

All side effects from my previous cancer treatments, except hair loss, are mild.

Exclusion Criteria

Positive serological test of hepatitis B virus (HBV) or hepatitis C virus at Screening

You are pregnant or currently breastfeeding.

I have not received any live vaccines in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1: Dose Escalation

T3011 administered intravenously as a single agent in subjects with solid tumors to evaluate escalating doses and assess toxicity

Variable, based on dose escalation and toxicity assessment

Phase 2a: Dose Expansion

An expansion study conducted based on phase 1 results to further evaluate safety and efficacy

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• T3011
• T3011 + pembrolizumab

Trial Overview The trial is testing T3011, both alone and combined with other therapies for treating various advanced solid tumors. It's an early-phase study that gradually increases the dose to find a safe level before expanding to more patients.

How Is the Trial Designed?

Group I: Phase 1 Experimental Treatment 1 Intervention

T3011 Single Agent Dose Escalation in participants with solid tumors

T3011 is already approved in United States, China for the following indications:

Approved in United States as MVR-T3011 for:

• Recurrent or metastatic head and neck squamous cell cancer (HNSCC) with disease progression after platinum-based chemotherapy and at least one prior line of anti–PD-1/PD-L1 therapy

Approved in China as MVR-T3011 for:

• High-risk BCG-failure non-muscle invasive bladder cancer (NMIBC)

Who Is Running the Clinical Trial?

ImmVira Pharma Co. Ltd

Lead Sponsor

Trials

6

Recruited

530+

Published Research Related to This Trial

In a phase II trial involving 50 patients with early triple-negative breast cancer, 66% achieved a pathological complete response (pCR) after treatment with nab-paclitaxel and pembrolizumab, indicating a promising efficacy of this combination therapy.

The treatment was associated with manageable side effects, with fatigue, peripheral sensory neuropathy, and neutropenia being the most common adverse events, suggesting that this regimen could be a viable alternative to platinum-based chemotherapy for patients who cannot tolerate it.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in combination with nab-paclitaxel for the treatment of patients with early-stage triple-negative breast cancer - A single-arm phase II trial (NeoImmunoboost, AGO-B-041). Fasching, PA., Hein, A., Kolberg, HC., et al.[2023]

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]

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

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]

The maximum tolerated doses (MTDs) for the combination of pembrolizumab and trametinib were established, with concurrent dosing showing a lower objective response rate (0%) compared to intermittent dosing (27%).

While the combination treatment had manageable safety profiles, with 31% of patients experiencing grade 3/4 treatment-related adverse events in the concurrent group, the overall antitumor activity was limited, suggesting that this combination may not be highly effective for solid tumors and BRAF wild-type melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KEYNOTE-022: Pembrolizumab with trametinib in patients with BRAF wild-type melanoma or advanced solid tumours irrespective of BRAF mutation. Maio, M., Carlino, MS., Joshua, AM., et al.[2022]

In a phase 3 trial involving 622 patients with metastatic triple-negative breast cancer, pembrolizumab did not significantly improve overall survival compared to standard chemotherapy, with median survival times of 9.9 months for pembrolizumab and 10.8 months for chemotherapy.

Pembrolizumab showed a manageable safety profile, with fewer severe treatment-related adverse events compared to chemotherapy, suggesting it may be safer for some patients despite not demonstrating superior efficacy overall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. Winer, EP., Lipatov, O., Im, SA., et al.[2021]

An elderly male patient on pembrolizumab developed four autoimmune toxicities, including type 1 diabetes and pneumonitis, highlighting the risk of multiple immune-related adverse events associated with this treatment.

The case suggests that aging may increase susceptibility to these adverse effects, necessitating close monitoring and prompt management, including stopping the immunotherapy and using steroids for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple autoimmune side effects of immune checkpoint inhibitors in a patient with metastatic melanoma receiving pembrolizumab. Kethireddy, N., Thomas, S., Bindal, P., et al.[2021]

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 the KEYNOTE-030 expanded access program, 979 patients with advanced melanoma received pembrolizumab, showing an objective response rate of 14.5%, indicating its efficacy in this difficult-to-treat population.

The treatment was generally well-tolerated, with 19.1% of patients experiencing treatment-related adverse events, but no treatment-related deaths were reported, supporting the safety of pembrolizumab for patients with advanced melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Pembrolizumab in Patients Enrolled in KEYNOTE-030 in the United States: An Expanded Access Program. Gangadhar, TC., Hwu, WJ., Postow, MA., et al.[2018]

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. 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 ...

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

Updated results from an ongoing phase 1/2a study of ... The efficacy of T3011 in immune-resistant melanoma was encouraging. Our data suggest T3011 may modify the tumor microenvironment and overcome ...

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

Intravenous T3011 Given as a Single Agent and in ... Results from the first Phase 1 study of MVR-T3011 as an intratumoral injection in patients with advanced solid tumors in the United States and Australia will be ...

5. prnewswire.com prnewswire.com/news-releases/esmo-2024---immvira-unveils-clinical-results-of-intravesical-mvr-t3011-for-high-risk-bcg-failure-nmibc-patients-302248442.html

ESMO 2024 - ImmVira Unveils Clinical Results of ... This Phase I, open-label, dose-escalation and expansion study was conducted in China to assess the safety and efficacy of MVR-T3011 administered ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05598268

A Study of T3011 Administered Via Intravenously in ... Primary Outcome Measures · Evaluate the safety and tolerability of escalating doses of IV T3011 in Patients with advanced malignant tumors, Incidence of AE(TEAE) ...

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 ...