Neoadjuvant Intralesional Injection of Talimogene Laherparepvec

Trial Title: Neoadjuvant Intralesional Injection of Talimogene Laherparepvec

NCT ID: NCT06660810

Condition: Soft Tissue Sarcoma
Sarcoma,Soft Tissue

Conditions: Official terms:
Sarcoma
Talimogene laherparepvec

Study type: Interventional

Study phase: Early Phase 1

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Talimogene Laherparepvec
Description: 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
Arm group label: Expansion Pilot

Intervention type: Radiation
Intervention name: Neoadjuvant Radiation
Description: 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
Arm group label: Expansion Pilot

Intervention type: Procedure
Intervention name: Surgery
Description: 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
Arm group label: Expansion Pilot

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.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Subject has provided informed consent - Histologically confirmed diagnosis of locally advanced STS subtypes (including undifferentiated pleomorphic sarcoma, myxofibrosarcoma, and malignant peripheral nerve sheath tumor (MPNST) that are unresectable with clear wide margins, for which preoperative radiotherapy is considered appropriate. - Previous treatment: prior systemic anti-cancer treatment consisting of chemotherapy, immunotherapy, or targeted therapy are allowed provided therapy completed at least 1 year prior to enrollment. - Age ≥ 18 years - Both men and women of all races and ethnic groups are eligible for this trial - ECOG performance status of ≤ 1 - 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) - Patient must have injectable disease (direct injection or ultrasound guided). Exclusion Criteria: - Sarcoma histologies that are not consistent with undifferentiated pleomorphic sarcoma, myxofibrosarcoma, or MPNST - History or evidence of sarcoma associated with immunodeficiency states (e.g.: Hereditary immune deficiency, HIV, organ transplant or leukemia). - Subjects with retroperitoneal and visceral sarcoma. - History or evidence of gastrointestinal inflammatory bowel disease (ulcerative colitis or Crohn's disease) or other symptomatic autoimmune disease including, inflammatory bowel disease, or history of any poorly controlled or severe systemic autoimmune disease (i.e., rheumatoid arthritis, systemic lupus erythematosus, scleroderma, type I diabetes, 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. - History of prior or current autoimmune disease. - History of prior or current splenectomy or splenic irradiation. - Active herpetic skin lesions - Require intermittent or chronic treatment with an anti-herpetic drug (e.g., acyclovir), other than intermittent topical use. - Any non-oncology vaccine therapies used for the prevention of infectious disease within 28 days prior to enrollment and during treatment period. - 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. - Known human immunodeficiency virus (HIV) disease (requires negative test for clinically suspected HIV infection). - 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). - 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. - 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. - 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). - Other investigational procedures while participating in this study that could affect the primary objective of the study as determined by the PI are excluded - Subject previously has entered this study. - Evidence of CNS metastases. - History of allergic reactions attributed to compounds of similar chemical or biologic composition to talimogene laherparepvec. - 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 - Patients on or requiring immunosuppressive therapies. - 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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: University of Iowa

Address:
City: Iowa City
Zip: 52242
Country: United States

Contact:
Last name: John Rieth, MD

Start date: December 1, 2024

Completion date: November 1, 2033

Lead sponsor:
Agency: John Rieth
Agency class: Other

Collaborator:
Agency: Amgen
Agency class: Industry

Source: University of Iowa

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06660810