Talimogene Laherparepvec + Nivolumab for Skin Cancer and Lymphoma

Recruiting at 37 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

68 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment Talimogene Laherparepvec + Nivolumab for skin cancer and lymphoma?

Research shows that Talimogene Laherparepvec (T-VEC) can improve survival in advanced melanoma and may work well with other immune therapies like Nivolumab. Combining T-VEC with immune checkpoint inhibitors has shown greater effectiveness in treating melanoma than using either treatment alone. ^{1 2 3 4 5}

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

Talimogene Laherparepvec (also known as T-VEC or Imlygic) has been studied in combination with other drugs like pembrolizumab and ipilimumab for advanced melanoma, showing an acceptable safety profile. While specific data on the combination with Nivolumab is not provided, the existing studies suggest that T-VEC is generally safe when used with similar immunotherapy drugs. ^{1 2 6 7 8}

What makes the drug Talimogene Laherparepvec + Nivolumab unique for skin cancer and lymphoma?

This drug combination is unique because Talimogene Laherparepvec is an oncolytic immunotherapy that works by directly injecting into tumors to destroy cancer cells and stimulate an immune response, while Nivolumab is an immune checkpoint inhibitor that helps the immune system attack cancer cells. Together, they may enhance each other's effects, offering a novel approach compared to standard treatments. ^{4 7 9 10 11}

What is the purpose of this trial?

This phase II trial studies how well talimogene laherparepvec and nivolumab work in treating patients with lymphomas that do not responded to treatment (refractory) or non-melanoma skin cancers that have spread to other places in the body (advanced) or do not responded to treatment. 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 nivolumab, 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 nivolumab may work better compared to usual treatments in treating patients with lymphomas or non-melanoma skin cancers.

Research Team

Ann (Annie) W Silk

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Eligibility Criteria

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

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

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

I still have side effects from previous cancer treatments.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

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

Talimogene Laherparepvec in Combination With Ipilimumab in Previously Untreated, Unresectable Stage IIIB-IV Melanoma. [2022]

2. England 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. [2022]

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

Successful treatment with intralesional talimogene laherparepvec in two patients with immune checkpoint inhibitor-refractory, advanced-stage melanoma. [2019]

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

Kaposi's varicelliform eruption in a patient with metastatic melanoma and primary cutaneous anaplastic large cell lymphoma treated with talimogene laherparepvec and nivolumab. [2019]

6. 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]

7. 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]

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

A Retrospective Chart Review Study of Real-World Use of Talimogene Laherparepvec in Unresectable Stage IIIB-IVM1a Melanoma in Four European Countries. [2021]

9. 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]

10. Switzerland 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). [2023]

11. 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]