Talimogene Laherparepvec + Pembrolizumab for Skin Cancer

Recruiting at 20 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Hepatitis, HIV, Autoimmune disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 27

Duration: Approximately 2 years

43 Participants Needed

Trial Summary

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 not have had surgery, biologic therapy, hormonal therapy, chemotherapy, targeted small molecule therapy, or radiation therapy within 14 days before joining the trial. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the treatment Talimogene Laherparepvec combined with Pembrolizumab for skin cancer?

Research shows that the combination of Talimogene Laherparepvec and Pembrolizumab has shown promising results in treating advanced melanoma, a type of skin cancer, with a good safety profile and encouraging response rates. Studies indicate that this combination may work better than using either treatment alone, without adding extra safety concerns. ^{1 2 3 4 5}

Is the combination of Talimogene Laherparepvec and Pembrolizumab safe for humans?

The combination of Talimogene Laherparepvec (T-VEC) and Pembrolizumab has shown an acceptable safety profile in patients with advanced melanoma, with most side effects being mild to moderate. Early results indicate that combining T-VEC with Pembrolizumab does not introduce additional safety concerns beyond those expected for each treatment alone. ^{1 3 4 5 6}

What makes the drug combination of Talimogene Laherparepvec and Pembrolizumab unique for treating skin cancer?

This treatment combines Talimogene Laherparepvec, a virus-based therapy that directly attacks cancer cells, with Pembrolizumab, an immune checkpoint inhibitor that boosts the immune system's ability to fight cancer. This combination is unique because it uses two different mechanisms to enhance the body's natural defenses against skin cancer. ^{7 8 9 10 11}

What is the purpose of this trial?

This phase II trial studies how well talimogene laherparepvec and pembrolizumab work in treating patients with stage III-IV melanoma. Biological therapies, such as talimogene laherparepvec, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop tumor cells from growing. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving talimogene laherparepvec and pembrolizumab may work better in treating patients with melanoma by shrinking the tumor.

Research Team

Siwen Hu-Lieskovan

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

This trial is for adults with stage III-IV melanoma who've had prior treatment with anti-PD-1 or anti-PD-L1 agents and saw their disease progress. They must have measurable disease, be in good physical condition, and agree to provide tissue samples. Exclusions include recent treatments, active autoimmune diseases requiring systemic treatment, uncontrolled illnesses that could limit compliance, pregnancy or nursing women.

Inclusion Criteria

As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

I have received anti-PD-1 or anti-PD-L1 treatment and my disease progressed after this treatment.

My melanoma is at an advanced stage and cannot be removed with surgery.

Exclusion Criteria

Patients must not have evidence of any clinically significant immunosuppression

I have not had any recent surgeries or therapies.

I do not have an active autoimmune disease needing systemic treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive talimogene laherparepvec intralesionally and pembrolizumab intravenously every 21 days for up to 36 cycles

Approximately 2 years

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

5 years

Every 6 months for 1 year, then annually

Treatment Details

Interventions

• Pembrolizumab
• Talimogene Laherparepvec

Trial Overview The study tests talimogene laherparepvec (a biological therapy) combined with pembrolizumab (an immunotherapy antibody), aiming to shrink tumors in advanced melanoma patients. It's a phase II trial exploring if this combination can stimulate the immune system more effectively than current treatments.

Participant Groups

Group I: Treatment (talimogene laherparepvec, pembrolizumab) Experimental Treatment 2 Interventions

Patients receive talimogene laherparepvec IL and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase III study involving 692 patients with advanced melanoma, the combination of talimogene laherparepvec (T-VEC) and pembrolizumab did not significantly improve progression-free survival (PFS) or overall survival (OS) compared to pembrolizumab alone.

The combination therapy showed a higher objective response rate (48.6% vs. 41.3%) and a similar safety profile to the placebo group, with grade ≥ 3 treatment-related adverse events occurring in about 20% of patients in both treatment arms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, Double-Blind, Placebo-Controlled, Global Phase III Trial of Talimogene Laherparepvec Combined With Pembrolizumab for Advanced Melanoma. Chesney, JA., Ribas, A., Long, GV., et al.[2023]

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 (PEM) significantly improved short-term treatment effectiveness and long-term survival rates in patients with advanced cutaneous malignant melanoma compared to chemotherapy with Temozolomide, with a notable increase in one-year survival rates (53.85% vs. 40.00%).

The use of PEM did not lead to a higher incidence of adverse reactions compared to the control group, indicating that it is a relatively safe treatment option for patients with this type of melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical application effect of Pembrolizumab in the treatment of advanced cutaneous malignant melanoma. Fu, L., Zhang, H., Jiang, J., et al.[2021]

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 (Keytruda) is an effective treatment for advanced melanoma, showing significant improvements in progression-free survival and overall response rates compared to ipilimumab and chemotherapy in clinical trials involving patients with varying treatment histories.

The drug has a manageable safety profile, with immune-related side effects that are generally reversible, making it a valuable option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: A Review in Advanced Melanoma. Deeks, ED.[2022]

Pembrolizumab (Keytruda) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

References

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

Randomized, Double-Blind, Placebo-Controlled, Global Phase III Trial of Talimogene Laherparepvec Combined With Pembrolizumab for Advanced Melanoma. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial. [2021]

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

Real-World Use of Talimogene Laherparepvec in German Patients with Stage IIIB to IVM1a Melanoma: A Retrospective Chart Review and Physician Survey. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Combining talimogene laherparepvec with immunotherapies in melanoma and other solid tumors. [2022]

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

Final analyses of OPTiM: a randomized phase III trial of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in unresectable stage III-IV melanoma. [2020]

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

Potential clinical and immunotherapeutic utility of talimogene laherparepvec for patients with melanoma after disease progression on immune checkpoint inhibitors and BRAF inhibitors. [2019]

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

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

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

Clinical application effect of Pembrolizumab in the treatment of advanced cutaneous malignant melanoma. [2021]

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

Pembrolizumab in the management of metastatic melanoma. [2020]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Pembrolizumab: A Review in Advanced Melanoma. [2022]

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

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. [2021]