Talimogene Laherparepvec + Nivolumab for Skin Cancer and Lymphoma

Not currently recruiting at 40 trial locations

Overseen By Janice M. Mehnert

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Antiherpetics

Disqualifiers: Melanoma, Leukemias, Autoimmune diseases, 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: 26

Duration: Up to 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining talimogene laherparepvec and nivolumab to treat certain skin cancers and lymphomas. The goal is to determine if these treatments can help when other therapies have failed, particularly in advanced cases where cancer has spread. Talimogene laherparepvec (also known as Imlygic, T-VEC, or Oncovex) uses substances from living organisms to potentially enhance the body's cancer-fighting ability, while nivolumab (also known as Opdivo) aids the immune system in targeting cancer cells. This trial may suit individuals with non-melanoma skin cancers or lymphomas unresponsive to standard treatments, especially if the cancer has spread or recurred. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had systemic therapy or radiotherapy within 3 weeks before starting the trial, and you should not be on certain immunosuppressive therapies. It's best to discuss your specific medications with the trial team.

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

Research has shown that talimogene laherparepvec (T-VEC) is generally safe and well-tolerated. In everyday use, it has been administered safely, with mostly mild side effects such as flu-like symptoms and injection site reactions. Studies on nivolumab also indicate it is well-tolerated, with some patients experiencing tiredness or skin rash, while serious reactions remain rare. Both treatments assist the immune system in fighting cancer. This trial is in phase 2, indicating that earlier tests demonstrated these treatments are safe enough for more people to try. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Talimogene Laherparepvec (T-VEC) and Nivolumab for treating skin cancer and lymphoma because they offer a new approach to battling these conditions. Unlike most treatments that target cancer cells directly, T-VEC is a genetically modified virus that specifically infects and kills cancer cells, while also stimulating the immune system to attack tumors. Nivolumab, on the other hand, is an immune checkpoint inhibitor that enhances the body's immune response against cancer cells. This combination not only targets cancer more precisely but also boosts the body’s natural defense mechanisms, offering a potentially more effective and less toxic treatment option compared to traditional chemotherapy and radiation.

What evidence suggests that talimogene laherparepvec and nivolumab might be effective for skin cancer and lymphoma?

Research has shown that using talimogene laherparepvec (T-VEC) with nivolumab may help treat certain cancers. T-VEC boosts the immune system to attack cancer cells. Studies have found that when T-VEC is combined with immune therapies like nivolumab, patients often experience better outcomes. Specifically, this combination has improved survival rates in people with advanced skin cancers. While T-VEC alone might not be effective for everyone, adding nivolumab enhances its efficacy. This trial will evaluate the combined treatment, offering hope for those with hard-to-treat lymphomas and non-melanoma skin cancers. ^{2 4 6 7 8}

Who Is on the Research Team?

Ann (Annie) W Silk

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with advanced or treatment-resistant non-melanoma skin cancers or lymphomas, excluding B-cell types. Participants must have measurable disease and at least one lesion suitable for injection. They should be in relatively good health (ECOG <=2), not pregnant, willing to use contraception, able to undergo biopsies, and have no significant immunosuppression or certain viral infections.

Inclusion Criteria

My cancer is non-melanoma skin cancer or a non-B-cell lymphoma.

My skin cancer is advanced or not responding to treatment.

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

I haven't had any cancer treatment in the last 3 weeks.

My cancer is not melanoma, sarcoma, leukemia, or lymphoma.

I still have side effects from previous cancer treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive talimogene laherparepvec intratumorally and nivolumab intravenously. Cycles repeat every 21 days for cycle 1 then every 14 days for up to 1 year.

Up to 1 year

Visits every 14-21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 12 weeks for 3 years.

3 years

Follow-up visits every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• Talimogene Laherparepvec

Trial Overview The study tests talimogene laherparepvec plus nivolumab against refractory lymphomas and advanced skin cancers. Talimogene uses modified viruses to stimulate the immune system while nivolumab blocks cancer's defenses against immune cells. The combination aims to enhance the body's ability to fight cancer.

How Is the Trial Designed?

Group I: Treatment (talimogene laherparepvec, nivolumab) Experimental Treatment 7 Interventions

Patients receive talimogene laherparepvec IT and nivolumab IV over 30 minutes on day 1. Cycles repeat every 21 days for cycle 1 then every 14 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo, CT scan or PET/CT on study. Patients also undergo blood sample collection and biopsies on study.

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

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

Talimogene laherparepvec (T-VEC) shows improved overall survival in patients with unresectable stage IIIB/C-IV melanoma, and when combined with CTLA-4 inhibitors like ipilimumab (T-VEC + IPI), it may offer even greater survival benefits.

An indirect comparison analysis indicated that while there was no significant difference in overall survival between T-VEC and T-VEC + IPI up to 15 months, extrapolated data suggested a substantial survival advantage for T-VEC + IPI at 48 months, with an expected survival rate of 81.1% compared to 32.0% for T-VEC alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there still a role for talimogene laherparepvec (T-VEC) in advanced melanoma? An indirect efficacy comparison of T-VEC plus ipilimumab combination therapy versus T-VEC alone as salvage therapy in unresectable metastatic melanoma. Fazel, M., AlRawashdh, N., Alamer, A., et al.[2022]

Talimogene laherparepvec (T-VEC) is an effective oncolytic immunotherapy for advanced melanoma, showing potential to elicit systemic antitumor immune responses even in patients who have not responded to anti-PD-1 and anti-CTLA-4 therapies.

In a case study involving two female patients with advanced melanoma who had previously progressed on immune checkpoint inhibitors, T-VEC treatment demonstrated successful outcomes, suggesting it may provide a complementary treatment option for those resistant to conventional immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment with intralesional talimogene laherparepvec in two patients with immune checkpoint inhibitor-refractory, advanced-stage melanoma. Seremet, T., Planken, S., Schwarze, JK., et al.[2019]

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]

In a phase 2 trial involving 39 patients with advanced sarcomas, the combination treatment of talimogene laherparepvec, trabectedin, and nivolumab showed a 12-month progression-free survival rate of 36.7%, indicating its potential efficacy in this difficult-to-treat cancer.

The treatment was associated with a manageable safety profile, with 50% of patients experiencing grade 3 or higher adverse events, suggesting that while there are risks, the combination therapy is worth further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of TNT: a phase 2 study using talimogene laherparepvec, nivolumab and trabectedin for previously treated patients with advanced sarcomas (NCT# 03886311). Chawla, SP., Tellez, WA., Chomoyan, H., et al.[2023]

This case study presents the first instance of combining immune checkpoint blockade (ICB) with Talimogene laherparepvec (T-VEC) in a patient suffering from both primary cutaneous anaplastic large cell lymphoma (pcALCL) and metastatic melanoma, showcasing the complexities of treating patients with multiple cancers.

The patient experienced rapid progression of pcALCL while on nivolumab, an anti-PD-1 therapy, and developed a novel adverse effect, Kaposi's varicelliform eruption, after the first dose of T-VEC, indicating potential safety concerns when using this treatment in patients with concurrent malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kaposi's varicelliform eruption in a patient with metastatic melanoma and primary cutaneous anaplastic large cell lymphoma treated with talimogene laherparepvec and nivolumab. Miller, DM., Trowbridge, RM., Desai, A., et al.[2019]

The combination of talimogene laherparepvec (T-VEC) and ipilimumab in patients with advanced melanoma showed a tolerable safety profile, with no dose-limiting toxicities and a manageable rate of grade 3/4 treatment-related adverse events (26.3%).

The treatment resulted in a 50% objective response rate, with 44% of patients experiencing a durable response lasting 6 months or more, indicating that this combination therapy may be more effective than using either treatment alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talimogene Laherparepvec in Combination With Ipilimumab in Previously Untreated, Unresectable Stage IIIB-IV Melanoma. Puzanov, I., Milhem, MM., Minor, D., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02978625

NCT02978625 | Talimogene Laherparepvec and ... Giving talimogene laherparepvec and nivolumab may work better compared to usual treatments in treating patients with lymphomas or non-melanoma skin cancers.

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

Talimogene laherparepvec: overview, combination therapy ... Combining T-VEC to promote tumor-derived antigen release with immunotherapies to treat regional and metastatic melanoma is increasingly being studied to ...

3. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A715

621 Interim analysis of a phase II study of talimogene ... Conclusions Analysis of data from Part I of this clinical trial suggests that T-VEC monotherapy did not translate to broad clinical efficacy ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT344767

Talimogene laherparepvec with systemic immunotherapy ... Our cohort suggests that TVEC is an effective treatment in combination with systemic immunotherapy, with a better overall survival observed with combination ...

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. clinicaltrials.gov clinicaltrials.gov/study/NCT02978625

NCT02978625 | Talimogene Laherparepvec and ... Giving talimogene laherparepvec and nivolumab may work better compared to usual treatments in treating patients with lymphomas or non-melanoma skin cancers.

7. jphcs.biomedcentral.com jphcs.biomedcentral.com/articles/10.1186/s40780-024-00388-0

Safety of talimogene laherparepvec: a real‐world ... Real-world outcomes of talimogene laherparepvec therapy: a multi-institutional experience. J Am Coll Surg. 2019;228(4):644–9. Article PubMed ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.e21549

Talimogene laherparepvec with systemic immunotherapy ... Our cohort suggests that TVEC is an effective treatment in combination with systemic immunotherapy, with a better overall survival observed with ...