T3011 + Pembrolizumab for Solid Cancers

Recruiting in Palo Alto (17 mi)

+8 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: ImmVira Pharma Co. Ltd

Must not be taking: HSV drugs, Live vaccines

Disqualifiers: Immunodeficiency, Autoimmune disease, Heart failure, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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 partients with advanced or metastatic solid tumors.

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.

What data supports the effectiveness of the drug Pembrolizumab in treating solid cancers?

Pembrolizumab has shown effectiveness in treating various solid tumors, including non-small cell lung cancer and advanced cancers with specific genetic features (MSI-H/dMMR), by helping the immune system attack cancer cells. It is approved for use in certain lung cancers and melanoma, indicating its potential benefit in solid cancers.

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What safety information is available for the treatment T3011 + Pembrolizumab?

Pembrolizumab, also known as Keytruda, has been associated with some side effects, including pneumonitis (lung inflammation) in 1%-5% of patients and a rare risk of type 1 diabetes in 0.2% of cases. Common side effects include fatigue, cough, nausea, and rash, while more serious immune-related side effects can affect organs like the lungs, liver, and thyroid.

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What makes the drug T3011 + Pembrolizumab unique for treating solid cancers?

The combination of T3011 and Pembrolizumab is unique because it combines a novel oncolytic virus (T3011) with a PD-1 inhibitor (Pembrolizumab), potentially enhancing the immune system's ability to attack cancer cells more effectively than using Pembrolizumab alone.

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Eligibility Criteria

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.

Trial Timeline

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

Participant Groups

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).

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Banner MD Anderson Cancer Center Gilbert, AZ

Dana Farber Cancer Institute Boston, MA

Mary Crowley Cancer Research Dallas, TX

University of Pittsburgh Medical Center Pittsburgh, PA

More Trial Locations

Who Is Running the Clinical Trial?

ImmVira Pharma Co. Ltd Lead Sponsor

References

1. 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] Pembrolizumab demonstrated durable antitumor activity in 233 patients with previously treated advanced microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) advanced solid tumors in the phase II multicohort KEYNOTE-158 (NCT02628067) study. Herein, we report safety and efficacy outcomes with longer follow-up for more patients with previously treated advanced MSI-H/dMMR noncolorectal cancers who were included in cohort K of the KEYNOTE-158 (NCT02628067) study.

2. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022] A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017] New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.

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

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. [2019] To evaluate safety, tolerability, and antitumor activity of pembrolizumab monotherapy in patients with programmed death ligand 1 (PD-L1)-expressing advanced ovarian cancer enrolled in the multicohort, phase Ib KEYNOTE-028 trial.

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022] Pembrolizumab (Keytruda; Merck Sharp & Dohme) is a humanized IgG4 monoclonal antibody used in cancer immunotherapy. It targets the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, immune checkpoint blockade is associated with a risk for immune-related adverse events (irAEs) potentially affecting the endocrine organs. Type 1 diabetes mellitus is a rare irAE of PD-1 inhibitors, occurring in 0.2% of cases.

6. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023] Pembrolizumab (Keytruda) is a monoclonal antibody against the programmed cell death-1 (PD-1) receptor on lymphocytes, which is one of the immune checkpoint inhibitors (ICIs) approved for multiple solid and hematologic malignancies. Although ICIs have proven to be more effective and less toxic compared to chemotherapy, there are reports of adverse side effects with ICIs. For example, pneumonitis is a potentially lethal side effect occurring in 1%-5% of patients who received ICIs in clinical trials, and there are case reports with clinical and radiological features of checkpoint inhibitor-pneumonitis (CIP).

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021] On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% confidence interval, 15-34); with 6 months of follow-up, 86% of responses were ongoing. The most common (≥20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. The benefits of the observed ORR with prolonged duration of responses outweighed the risks of immune-mediated adverse reactions in this life-threatening disease and represented an improvement over available therapy. Important regulatory issues in this application were role of durability of response in the evaluation of ORR for accelerated approval, reliance on data from a first-in-human trial, and strategies for dose selection. Clin Cancer Res; 23(19); 5666-70. ©2017 AACR.

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

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. [2022] Nivolumab (Opdivo, Bristol Meyer Squibb, New York, NY) and pembrolizumab (Keytruda, Merck, Kenilworth, NJ) are the first two US Food and Drug Administration (FDA)-approved monoclonal antibodies targeting programmed death-1 (PD-1). Nivolumab and pembrolizumab work by interfering with the interaction between PD-1 and programmed death ligand-1 (PD-L1), whose unimpeded interaction downregulates T cells allowing cancer cells to evade immune surveillance. These drugs have earned a series of FDA approvals for melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell cancer (HNSCC), urothelial cancer, classical Hodgkin lymphoma, and renal cell cancer. In this review we will summarize the data for efficacy and toxicity for these two agents. We conclude that they represent two valuable but interchangeable alternatives to target their approved indications. We will discuss how this can help global payers seeking to contain the cost of cancer therapeutics that continues to spiral out of control.

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

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017] Pembrolizumab (MK-3475) is a monoclonal antibody that binds to the PD-1 receptor on T cells and prevents binding to its ligands PD-L1 and PD-L2. Blocking this receptor frees T cells from the inhibitory effects of PD-L1 and allows them to mediate antitumor effects against cancer cells. In a large Phase I study of 411 patients with melanoma, high durable response rates over a range of doses and schedules have been shown with very little toxicity. A Phase III study of pembrolizumab comparing two schedules of administration with the current standard treatment with the anti-CTLA-4 monoclonal antibody is in progress. Combinations with other checkpoint inhibitors as well as other anticancer agents are also being evaluated. Approval of pembrolizumab for the treatment of melanoma is expected.

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] Pembrolizumab is a programmed cell death protein-1 (PD-1) inhibitor used to treat advanced patients with non-small cell lung cancer (NSCLC) with a programmed cell death ligand-1 (PD-L1) tumour proportion score (TPS) ≥50. Further sub-division of TPS-based stratification has not been evaluated in the UK, although smoking-induced tumour mutational burden and the immunogenic effects of prior radiotherapy are suggested to improve response.