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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safety and tolerability of a treatment combining radiotherapy and talimogene laherparepvec, a cancer-fighting virus, for individuals with certain types of sarcoma, a cancer that forms in bones and soft tissues. The study will assess the effectiveness of this combination for those whose sarcomas cannot be surgically removed with clear margins. It is suitable for individuals with locally advanced soft tissue sarcoma that cannot be completely removed with surgery and who have not previously received talimogene laherparepvec or radiation to the same tumor area. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

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

Research shows that talimogene laherparepvec, or T-VEC, is generally well-tolerated. This treatment uses a virus to specifically target and destroy cancer cells. Some patients experience side effects like flu-like symptoms, tiredness, and reactions at the injection site, but these are usually mild to moderate.

When combined with radiation therapy, T-VEC remains safe. Studies have found that this combination can effectively shrink tumors while keeping side effects manageable. This suggests that the treatment can be safely used in patients, although individual experiences may differ.

Overall, while talimogene laherparepvec appears promising, potential trial participants should discuss any concerns with their healthcare team to understand how this treatment might affect them personally. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Talimogene laherparepvec (TVEC) is unique because it combines cutting-edge virotherapy with traditional radiotherapy to tackle sarcoma. Unlike standard treatments like surgery, chemotherapy, or standalone radiotherapy, TVEC uses a modified virus designed to infect and destroy cancer cells while sparing healthy ones. This innovative approach also stimulates the immune system to recognize and attack the tumor, potentially leading to more effective and lasting results. Researchers are excited about TVEC as it offers a dual mechanism of direct cancer cell destruction and immune system activation, which could significantly improve outcomes for patients with sarcoma.

What evidence suggests that this trial's treatments could be effective for sarcoma?

Research has shown that talimogene laherparepvec (T-VEC) may help treat certain cancers. In one study, about 43.5% of patients experienced complete tumor disappearance. Another study found that 29.1% of patients had a lasting complete response, with no cancer recurrence. This trial will explore the combination of T-VEC with radiotherapy to determine if it can further improve outcomes for people with advanced sarcoma. Researchers aim to understand how this combination might enhance cancer treatment results. ^{4 5 6 7 8}

Who Is on the Research Team?

John Rieth, MD

Principal Investigator

University of Iowa Holden Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

Citations

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Talimogene Laherparepvec (T-VEC): An Intralesional ... With a median follow-up time of 8.6 months, 23 patients were evaluated for response: 10 patients (43.5%) achieved a CR and 3 (13.1%) a PR, with ...

2. imlygic.com imlygic.com/efficacy-clinical-trial-results

Efficacy & Clinical Results Of the 48 patients who achieved a durable response with IMLYGIC®, 14 patients (29.1%) had a durable complete response. This means that all evidence of ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.11570

A phase II study of talimogene laherparepvec (T-VEC) and ... The open-label, single-center phase II study of T-VEC and pembrolizumab in patients with advanced sarcoma met its primary endpoint and demonstrated a best ...

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

Final 5-Year Follow-Up Results Evaluating Neoadjuvant ... These results demonstrate that neoadjuvant T-VEC plus surgery improves cancer-related outcomes vs surgery alone, with acceptable safety. The ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT403760

Interim results of a phase 2 study using talimogene ... 1 = 2 PR, 9 SD (BOR Rate 18.2%). The disease control rate (PR+SD) at week 6 was 100%. The median PFS was 7 months (range: 3- 18); 6-month PFS rate, 55%; median ...

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Talimogene laherparepvec: overview, combination therapy ... Talimogene laherparepvec selectively replicates within and lyses tumor cells while producing granulocyte macrophage colony-stimulating factor, which may promote ...

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. clinicaltrials.gov clinicaltrials.gov/study/NCT02923778

Talimogene Laherparepvec and Radiation Therapy in ... This phase II trial studies the side effects of talimogene laherparepvec and radiation therapy and to see how well they work in treating patients with newly ...