TVEC + Radiotherapy for Sarcoma

Overseen By Varun Monga, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: John Rieth

Must not be taking: Anti-herpetics, Anticoagulants

Disqualifiers: HIV, Hepatitis B/C, Autoimmune diseases, others

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

Compensation: Varies

Number of Visits: Unknown

8 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to determine the safety and tolerability of talimogene laherparepvec when combined with radiation therapy. Approximately 46 people will take part in this study conducted by investigators at the University of Iowa.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take anti-herpetic drugs or therapeutic anticoagulants like warfarin. If you're on low molecular weight heparin, you may need to adjust the timing of your dose.

What data supports the effectiveness of the treatment TVEC + Radiotherapy for Sarcoma?

Research shows that talimogene laherparepvec (TVEC), when used in combination with other treatments, can enhance the immune system's ability to fight tumors. It has been effective in treating advanced melanoma and shows promise in increasing immune activation in sarcoma, suggesting potential benefits when combined with radiotherapy for sarcoma. ^{1 2 3 4 5}

Is the combination of TVEC and radiotherapy safe for humans?

Talimogene laherparepvec (T-VEC) has been studied for safety in patients with melanoma, showing that most side effects were mild, such as chills and nausea, with a few severe cases like vomiting and wound infection. It is approved for use in the US, EU, and Australia, indicating a generally acceptable safety profile. ^{6 7 8 9 10}

How does the TVEC + Radiotherapy treatment for sarcoma differ from other treatments?

The TVEC + Radiotherapy treatment is unique because it combines an oncolytic virus (a virus that targets and destroys cancer cells) called Talimogene Laherparepvec (T-VEC) with radiotherapy, potentially enhancing the immune response against tumors. This approach is novel compared to traditional treatments that typically do not use viral therapy to stimulate the immune system. ^{11 12 13 14 15}

Research Team

John Rieth, MD

Principal Investigator

University of Iowa Holden Comprehensive Cancer Center

Eligibility Criteria

Adults with a specific type of cancer called locally advanced soft tissue sarcoma (STS) that can't be completely removed by surgery. They should have tumors at least 5 cm in size suitable for radiation and direct injection or ultrasound-guided therapy. Participants must not have had certain treatments, vaccines, or other clinical trials recently and cannot have autoimmune diseases, active infections like HIV or hepatitis, or severe health issues.

Inclusion Criteria

Subject has provided informed consent.

I finished any cancer treatments like chemotherapy or immunotherapy over a year ago.

My cancer is not GIST, Desmoid, Ewing sarcoma, Kaposi sarcoma, bone sarcomas, or Grade 1 myxoid liposarcoma.

Exclusion Criteria

Positive HBV surface antigen (indicative for chronic hepatitis B or recent acute hepatitis B).

Patients who are receiving any other investigational agents.

Creatinine > 2.0 × ULN

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation and Intratumoral Injection

Participants receive neoadjuvant radiation and weekly intratumoral injections of talimogene laherparepvec

6-8 weeks

Weekly visits for injections

Surgery

Surgery is performed 4-6 weeks after the end of radiation therapy

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• Radiotherapy
• Talimogene Laherparepvec

Trial Overview The trial is testing the safety and how well people tolerate combining talimogene laherparepvec (a type of oncolytic virus therapy) with radiation therapy in treating STS. About 46 participants will receive this combination treatment to see if it's an effective pre-surgical option.

Participant Groups

Group I: Talimogene Laherparepvec in combination with radiotherapy-Phase I Cohort Experimental Treatment 2 Interventions

Talimogene Laherparepvec Dose Levels: Dose 0 = talimogene laherparepvec up to 8.0 mL of 108 PFU/mL dosed weekly Dose -1 = talimogene laherparepvec up to 8.0 mL of 108 PFU/mL dosed every 2 weeks

Group II: Talimogene Laherparepvec in combination with radiotherapy-Phase II Cohort Active Control 2 Interventions

Dose 0 = talimogene laherparepvec up to 8.0 mL of 108 PFU/mL dosed weekly

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

Approved in European Union as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in United States as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in Canada as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in Japan as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in China as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in Switzerland as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Who Is Running the Clinical Trial?

John Rieth

Lead Sponsor

Trials

4

Recruited

70+

Varun Monga, MD

Lead Sponsor

Trials

7

Recruited

130+

Mohammed Milhem

Lead Sponsor

Trials

9

Recruited

240+

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Findings from Research

In a phase 2 trial involving 20 patients with advanced sarcoma, the combination of talimogene laherparepvec (T-VEC) and pembrolizumab achieved a 30% objective response rate at 24 weeks, indicating promising antitumor activity.

The treatment demonstrated a manageable safety profile, with only 20% of patients experiencing grade 3 treatment-related adverse events and no grade 4 events or treatment-related deaths, suggesting it is a safe option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Objective Response Rate Among Patients With Locally Advanced or Metastatic Sarcoma Treated With Talimogene Laherparepvec in Combination With Pembrolizumab: A Phase 2 Clinical Trial. Kelly, CM., Antonescu, CR., Bowler, T., et al.[2023]

In a phase Ib study involving 34 patients with triple negative breast cancer (TNBC) and colorectal cancer (CRC) with liver metastases, the combination of talimogene laherparepvec (T-VEC) and atezolizumab showed a manageable safety profile, with no dose-limiting toxicities in TNBC patients and a 17% incidence in CRC patients, primarily involving serious adverse events.

Despite the safety of the combination treatment, the efficacy was limited, with only a 10% overall response rate in TNBC and no responses in CRC, indicating that while the treatment is safe, it may not provide significant antitumor benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib study of talimogene laherparepvec in combination with atezolizumab in patients with triple negative breast cancer and colorectal cancer with liver metastases. Hecht, JR., Raman, SS., Chan, A., et al.[2023]

In a phase 2 study involving 60 patients with advanced melanoma, talimogene laherparepvec (T-VEC) was found to be safely administered with minimal risk of transmission to close contacts when proper occlusive dressings were used.

T-VEC DNA was primarily detected in injected lesions and blood during treatment, but only a small percentage showed infectivity, indicating that while the virus is present, the risk of spreading it to others is low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biodistribution, shedding, and transmissibility of the oncolytic virus talimogene laherparepvec in patients with melanoma. Andtbacka, RHI., Amatruda, T., Nemunaitis, J., et al.[2020]

Talimogene laherparepvec (T-VEC) is an effective treatment for advanced melanoma, showing an overall response rate of 26% and significantly improving the durable response rate compared to granulocyte-macrophage colony-stimulating factor (16.3% vs 2.1%).

T-VEC is generally well tolerated with mild to moderate adverse effects, and while it does not significantly improve median overall survival compared to other treatments, it is the first approved oncolytic virus for local treatment of melanoma lesions, with ongoing trials exploring its use in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talimogene Laherparepvec: An Oncolytic Virus Therapy for Melanoma. Corrigan, PA., Beaulieu, C., Patel, RB., et al.[2018]

Talimogene laherparepvec, a genetically modified herpes virus used as an oncolytic immunotherapy, was administered to 41 melanoma patients, showing a safety profile similar to previous trials, with only 7.3% experiencing severe treatment-related adverse events.

The treatment led to complete responses in five patients, and the therapy is now approved for use in the US, EU, and Australia, indicating its efficacy in managing unresectable melanoma tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IIIb safety results from an expanded-access protocol of talimogene laherparepvec for patients with unresected, stage IIIB-IVM1c melanoma. Chesney, J., Awasthi, S., Curti, B., et al.[2018]

In a study involving 76 patients treated with talimogene laherparepvec (T-VEC) for unresectable melanoma, 20% achieved complete response with no remaining injectable lesions, indicating its efficacy in clinical practice.

T-VEC was well tolerated, with flu-like symptoms being the most common side effect in only 10.5% of patients, and no serious infections reported, highlighting its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Observational study of talimogene laherparepvec use for melanoma in clinical practice in the United States (COSMUS-1). Perez, MC., Zager, JS., Amatruda, T., et al.[2022]

Talimogene laherparepvec (T-VEC) showed a significant drop in efficacy from preclinical studies, which reported up to 100% complete regression in tumors, to clinical studies where the highest complete response rate was only 24%.

The study highlighted a high risk of bias in both preclinical and clinical studies, indicating that the promising results seen in the lab may not translate effectively to patient outcomes, underscoring the need for more rigorous and transparent research methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mapping the preclinical to clinical evidence and development trajectory of the oncolytic virus talimogene laherparepvec (T-VEC): a systematic review. Lalu, M., Leung, GJ., Dong, YY., et al.[2020]

In a phase II study of 46 patients with locally advanced rectal cancer, a sequential schedule of administering bevacizumab before chemotherapy resulted in a 50% rate of complete tumor regression, significantly higher than the 12.5% observed with the concomitant schedule.

The sequential schedule also showed a lower incidence of severe neutropenia (30% vs. 44%) and fewer postoperative complications (28% vs. 53%), indicating a potentially safer and more effective treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical role of bevacizumab scheduling in combination with pre-surgical chemo-radiotherapy in MRI-defined high-risk locally advanced rectal cancer: Results of the BRANCH trial. Avallone, A., Pecori, B., Bianco, F., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Intratumoral talimogene laherparepvec injection with concurrent preoperative radiation in patients with locally advanced soft-tissue sarcoma of the trunk and extremities: phase IB/II trial. [2022]

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

Objective Response Rate Among Patients With Locally Advanced or Metastatic Sarcoma Treated With Talimogene Laherparepvec in Combination With Pembrolizumab: A Phase 2 Clinical Trial. [2023]

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

Phase Ib study of talimogene laherparepvec in combination with atezolizumab in patients with triple negative breast cancer and colorectal cancer with liver metastases. [2023]

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

Talimogene Laherparepvec (TVEC) for the Treatment of Advanced Melanoma: A Single-Institution Experience. [2022]

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

Real-World Outcomes of Talimogene Laherparepvec Therapy: A Multi-Institutional Experience. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Biodistribution, shedding, and transmissibility of the oncolytic virus talimogene laherparepvec in patients with melanoma. [2020]

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

Talimogene Laherparepvec: An Oncolytic Virus Therapy for Melanoma. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Phase IIIb safety results from an expanded-access protocol of talimogene laherparepvec for patients with unresected, stage IIIB-IVM1c melanoma. [2018]

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

Observational study of talimogene laherparepvec use for melanoma in clinical practice in the United States (COSMUS-1). [2022]

10. England pubmed.ncbi.nlm.nih.gov

Mapping the preclinical to clinical evidence and development trajectory of the oncolytic virus talimogene laherparepvec (T-VEC): a systematic review. [2020]

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

A Phase I Trial of Talimogene Laherparepvec in Combination with Neoadjuvant Chemotherapy for the Treatment of Nonmetastatic Triple-Negative Breast Cancer. [2022]

12. England pubmed.ncbi.nlm.nih.gov

A phase II study of talimogene laherparepvec for patients with inoperable locoregional recurrence of breast cancer. [2022]

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

Oncolytic T-VEC virotherapy plus neoadjuvant chemotherapy in nonmetastatic triple-negative breast cancer: a phase 2 trial. [2023]

14. England pubmed.ncbi.nlm.nih.gov

Preoperative short-course radiotherapy versus combined radiochemotherapy in locally advanced rectal cancer: a multi-centre prospectively randomised study of the Berlin Cancer Society. [2021]

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

Critical role of bevacizumab scheduling in combination with pre-surgical chemo-radiotherapy in MRI-defined high-risk locally advanced rectal cancer: Results of the BRANCH trial. [2022]