Neoadjuvant Intralesional Injection of Talimogene Laherparepvec

NCT ID: NCT06660810

Last Updated: 2026-01-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-03-03
• Study Completion Date: 2030-03-10

Brief Summary

The proposed study is designed to treat locally advanced soft tissue sarcoma (STS) subtypes with neoadjuvant talimogene laherparepvec (TVEC) and preoperative external beam radiation therapy (EBRT).

Detailed Description

This is a single-arm open-label phase Ib and phase II clinical study assessing the safety and relative efficacy of concurrent talimogene laherparepvec in combination with radiotherapy in patients with soft tissue sarcomas. Patients will be treated with neoadjuvant radiation and weekly intratumoral injections of talimogene laherparepvec. Weekly injections of talimogene laherparepvec will be continued until surgery. Surgery will be performed 4-6 weeks from the end of radiation therapy to allow for resolution of acute toxicities per current standard of care.

Conditions

Soft Tissue Sarcoma; Sarcoma,Soft Tissue

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Expansion Pilot

Patients will be treated with neoadjuvant radiation and weekly intratumoral injections of talimogene laherparepvec. Weekly injections of talimogene laherparepvec will be continued until surgery. Surgery will be performed 4-6 weeks from the end of radiation therapy to allow for resolution of acute toxicities per current standard of care

Group Type: EXPERIMENTAL

Talimogene Laherparepvec

Intervention Type: DRUG

Talimogene laherparepvec (HSV-1 [strain JS1]/ICP34.5-/ICP47-/hGM-CSF) is an oncolytic immunotherapy, formerly known as OncoVEXGM-CSF, an immune-enhanced, oncolytic herpes simplex virus type 1 (HSV-1)

Patients will be treated with neoadjuvant radiation and weekly intratumoral injections of talimogene laherparepvec

Neoadjuvant Radiation

Intervention Type: RADIATION

Treatment given as a first step to shrink a tumor before the main treatment, which is usually surgery, is given.

Patients will be treated with neoadjuvant radiation and weekly intratumoral injections of talimogene laherparepvec

Surgery

Intervention Type: PROCEDURE

Surgery will be performed 4-6 weeks from the end of radiation therapy to allow for resolution of acute toxicities per current standard of care

Interventions

Talimogene Laherparepvec

Talimogene laherparepvec (HSV-1 [strain JS1]/ICP34.5-/ICP47-/hGM-CSF) is an oncolytic immunotherapy, formerly known as OncoVEXGM-CSF, an immune-enhanced, oncolytic herpes simplex virus type 1 (HSV-1)

Patients will be treated with neoadjuvant radiation and weekly intratumoral injections of talimogene laherparepvec

Intervention Type: DRUG

Neoadjuvant Radiation

Treatment given as a first step to shrink a tumor before the main treatment, which is usually surgery, is given.

Patients will be treated with neoadjuvant radiation and weekly intratumoral injections of talimogene laherparepvec

Intervention Type: RADIATION

Surgery

Surgery will be performed 4-6 weeks from the end of radiation therapy to allow for resolution of acute toxicities per current standard of care

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

6. ECOG performance status ≤1.

7. Patient must have measurable disease:

•Tumor size at least ≥ 5 cm in the longest diameter as measured by CT scan or MRI for which radiation is feasible.

8. Patient must have injectable disease (direct injection or ultrasound guided).

Exclusion Criteria

1. Sarcoma histologies that are not consistent with undifferentiated pleomorphic sarcoma, myxofibrosarcoma, or MPNST

2. History or evidence of sarcoma associated with immunodeficiency states (e.g.:Hereditary immune deficiency, HIV, organ transplant or leukemia).

3. Subjects with retroperitoneal and visceral sarcoma.

4. History or evidence of uncontrolled gastrointestinal inflammatory bowel disease (ulcerative colitis or Crohn's disease) or other symptomatic uncontrolled autoimmune disease including, inflammatory bowel disease, or history of any poorly controlled or severe systemic autoimmune disease (i.e., severe rheumatoid arthritis requiring biologic treatment, systemic lupus erythematosus, scleroderma, or autoimmune vasculitis).

History of other malignancy within the past 3 years except treated with curative intent and no known active disease present and has not received chemotherapy for ≥ 1 year before enrollment/randomization and low risk for recurrence.

5. History of prior or current splenectomy or splenic irradiation.

6. Active herpetic skin lesions

7. Require intermittent or chronic treatment with an anti-herpetic drug (e.g., acyclovir), other than intermittent topical use.

8. Any non-oncology vaccine therapies used for the prevention of infectious disease within 28 days prior to enrollment and during treatment period.

9. Concomitant treatment with therapeutic anticoagulants such as warfarin. Patients on therapeutic low molecular weight heparin may be allowed provided the dose can be safely held as per the treating investigator on the morning of scheduled intratumoral injection and can be resumed 12 hours after the procedure.

10. Known human immunodeficiency virus (HIV) disease (requires negative test for clinically suspected HIV infection).

11. Acute or chronic hepatitis B or hepatitis C infection (requires negative test for clinically suspected hepatitis B or hepatitis C infection).

• Evidence of hepatitis B -

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

2. Negative HBV surface antigen but positive HBV total core antibody (indicative for resolved hepatitis B infection or occult hepatitis B) and detectable copies of HBV DNA by PCR (detectable HBV DNA copies suggest occult hepatitis B).

• Evidence of hepatitis C - a)Positive HCV antibody and positive HCV RNA by PCR (undetectable RNA copies suggest past and resolved hepatitis C infection).

12. Female subjects who are pregnant or breast-feeding or planning to become pregnant during study treatment and through 3 months after the last dose of study treatment.

13. Female subjects of childbearing potential or male subjects who are unwilling to use 2 highly effective methods of contraception during study treatment and through 3 months after the last dose of study treatment. See Section 8.5 for more details.

14. Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s).

15. Other investigational procedures while participating in this study that could affect the primary objective of the study as determined by the PI are excluded

16. Subject previously has entered this study.

17. Evidence of CNS metastases.

18. History of allergic reactions attributed to compounds of similar chemical or biologic composition to talimogene laherparepvec.

19. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

20. Patients on or requiring immunosuppressive therapies.

21. Any of the following laboratory abnormalities:

• Hemoglobin < 9.0 g/dL
• Absolute neutrophil count (ANC) < 1500 per mm3
• Platelet count < 100,000 per mm3
• Total bilirubin > 1.5 × ULN
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × ULN
• Alkaline phosphatase > 2.5 × ULN
• PT (or INR) and PTT (or aPTT) > 1.5 × ULN
• Creatinine > 2.0 × ULN

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: collaborator

John Rieth

OTHER

Sponsor Role: lead

Responsible Party

John Rieth

Clinical Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

John Rieth, MD

Role: PRINCIPAL_INVESTIGATOR

University of Iowa

Locations

University of Iowa

Iowa City, Iowa, United States

Countries

United States

Other Identifiers

202402722

Identifier Type: -

Identifier Source: org_study_id