Talimogene Laherparepvec + Pembrolizumab for Skin Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of combining talimogene laherparepvec and pembrolizumab for individuals with advanced melanoma, a type of skin cancer. Talimogene laherparepvec is a biological therapy that may help the immune system combat cancer cells, while pembrolizumab is an immunotherapy designed to enhance the body's ability to attack cancer. The trial targets individuals with stage III or IV melanoma who have previously received certain immune therapies but whose cancer continued to progress. Participants should have melanoma unsuitable for surgery or other local treatments intended to cure. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in melanoma 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 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.

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

Research shows that the combination of talimogene laherparepvec (T-VEC) and pembrolizumab is generally safe for people with melanoma. Previous studies found that this treatment pair has an acceptable safety profile, meaning it usually doesn't cause unexpected or severe side effects for most people.

Specifically, studies have shown that these treatments are well-tolerated, even in patients whose melanoma returned after other treatments. Most people can undergo the treatment without serious problems.

While any treatment can have side effects, the data so far reassures those considering joining a trial with this combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Talimogene Laherparepvec and Pembrolizumab for skin cancer because it offers a novel approach to treatment. Unlike standard therapies like chemotherapy or radiation, Talimogene Laherparepvec is a genetically modified virus designed to selectively infect and destroy cancer cells, boosting the immune response. Pembrolizumab, an immune checkpoint inhibitor, further enhances this effect by helping the immune system recognize and attack cancer cells more effectively. This dual-action strategy not only targets the cancer directly but also empowers the body's own defenses to fight the disease, potentially improving outcomes for patients with skin cancer.

What evidence suggests that talimogene laherparepvec and pembrolizumab might be effective for melanoma?

Research has shown that using talimogene laherparepvec (T-VEC) with pembrolizumab may help treat advanced melanoma. In this trial, participants will receive the combination of T-VEC and pembrolizumab. Studies have found that this combination is generally safe and has led to complete recovery in some patients. T-VEC uses a virus to attack cancer cells and boost the immune system, while pembrolizumab is an immunotherapy that helps the immune system fight cancer. Together, they may enhance the body's ability to combat melanoma by shrinking tumors and stopping their growth. ^{1 4 5 6 7}

Who Is on the Research Team?

Siwen Hu-Lieskovan

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 (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 (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 (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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.00343

Randomized, Double-Blind, Placebo-Controlled, Global ... The combination of talimogene laherparepvec (T-VEC) and pembrolizumab previously demonstrated an acceptable safety profile and an encouraging complete response ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6094674/

Talimogene laherparepvec: overview, combination therapy ... Another combination therapy currently being studied, combines pembrolizumab with T-VEC in stage IIIB/IIIC and IV melanoma. The multicenter Phase Ib/III trial ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02263508

Study Details | NCT02263508 | Pembrolizumab With ... The primary objective of Phase 3 are to evaluate the efficacy of talimogene laherparepvec with pembrolizumab versus placebo with pembrolizumab, as assessed by ...

4. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2808227

Final 5-Year Follow-Up Results Evaluating Neoadjuvant ... The phase 3 OPTiM trial of T-VEC monotherapy for advanced melanoma showed a significantly improved durable response over granulocyte-macrophage colony- ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2950247024001294

Real-world outcomes with T-VEC in patients with anti-PD-1 ... This study evaluates the outcomes of the use of talimogene laherparepvec (T-VEC), an oncolytic virus therapy, in patients with in-transit melanoma and Merkel ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38870745/

Open-label, phase II study of talimogene laherparepvec ... Conclusion: T-VEC-pembrolizumab demonstrated antitumor activity and tolerability in PD-1-refractory melanoma, specifically in patients with disease recurrence ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04068181?tab=results

Study Results | NCT04068181 | Talimogene ... Safety Analysis Set: All enrolled participants who received at least 1 dose of talimogene laherparepvec or pembrolizumab. Baseline Analysis Population ...