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

Trial Summary

What is the purpose of this trial?

A Phase 1/2a Open-Label Dose Escalation and Dose Expansion Study of T3011 when Administered Intravenously as a Single Agent and in Combination with Other Therapy in Subjects with Advanced Solid Tumors

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.

What data supports the effectiveness of the drug T3011 + pembrolizumab for advanced cancers?

Pembrolizumab has shown effectiveness in treating various advanced cancers, such as melanoma and non-small cell lung cancer, by helping the immune system attack cancer cells. It has demonstrated durable antitumor activity in patients with certain genetic markers, like high microsatellite instability, across different types of advanced solid tumors. ^{1 2 3 4 5}

Is the combination of T3011 and pembrolizumab safe for humans?

There is no specific safety data available for the combination of T3011 and pembrolizumab. However, pembrolizumab alone has been shown to be generally safe in humans, with common side effects including fatigue, rash, itching, and diarrhea, and less common immune-related side effects like inflammation of the lungs, liver, or thyroid. ^{3 6 7 8 9}

What makes the drug T3011 + Pembrolizumab unique for advanced cancers?

The combination of T3011 and pembrolizumab is unique because it combines a novel oncolytic virus (T3011) with an immune checkpoint inhibitor (pembrolizumab), potentially enhancing the immune system's ability to attack cancer cells more effectively than either treatment alone. ^{1 10 11 12 13}

Eligibility Criteria

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.

I am 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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 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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]

2. Singapore pubmed.ncbi.nlm.nih.gov

Clinical outcomes of pembrolizumab therapy in advanced-NSCLC patients with poor performance status (≥3) and high PD-L1 expression (TPS ≥50%): A case series. [2021]

3. England 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. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Pembrolizumab in Patients Enrolled in KEYNOTE-030 in the United States: An Expanded Access Program. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. [2020]

8. England 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. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Multiple autoimmune side effects of immune checkpoint inhibitors in a patient with metastatic melanoma receiving pembrolizumab. [2021]

10. England 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. [2023]

11. China pubmed.ncbi.nlm.nih.gov

KRASG12C/TP53 co-mutations identify long-term responders to first line palliative treatment with pembrolizumab monotherapy in PD-L1 high (≥50%) lung adenocarcinoma. [2022]

12. England 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). [2023]

13. England pubmed.ncbi.nlm.nih.gov

A different type of acute myocarditis: a case report of acute autoimmune myocarditis mediated by anti-PD-1 T lymphocyte receptor (pembrolizumab). [2022]