Talimogene Laherparepvec, Nivolumab and Trabectedin for Sarcoma

NCT03886311 | Recruiting Phase 2 FDA Drug

• 1 other identifier: SOC-1882
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 2 study using talimogene laherparepvec, nivolumab, and trabectedin as first, second or third line therapy for advanced sarcoma, including desmoid tumor and chordoma.

Conditions

Sarcoma

Keywords

marine derived alkaloid; PD1 inhibitor; CTLA4 inhibitor

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Progression free survival at month 12

  12 months

Secondary Outcomes (5)

• Best overall response and duration of response

  12 months

• Progression free survival rate

  Nine months

• )verall survival rate

  12 months

• Convesion to resectable tumor

  12 months

• Incidence of adverse events

  12 months

Study Arms (1)

Talimogene laherparepvec, Nivolumab and Trabectedin

EXPERIMENTAL

This is an open label phase 2 study using known doses of TALIMOGENE LAHERPAREPVEC injected intratumorally, and NIVOLUMAB AND TRABECTEDIN given intravenously. A total of 40 previously untreated and treated patients will receive TRABECTEDIN 1.2 mg/m2 CIV over 24 hours q3 weeks, NIVOLUMAB 240 mg IV over 30 min q 2 weeks and TALIMOGENE LAHERPAREPVEC intratumorally q 2 weeks according to tumor size (see Schematic of Study Design and Imlygic product information; www.accessdata.fda.gov). Patients in this study may continue treatment until significant disease progression (see below for criteria for discontinuation of therapy) or unacceptable toxicity occurs up to one year of therapy.

Drug: Talimogene Laherparepvec 100000000 PFU/1 ML Injection Suspension [IMLYGIC]; Drug: Nivolumab IV Soln 100 MG/10ML; Drug: Trabectedin 0.25 MG/1 VIAL Intravenous Powder for Solution

Interventions

Talimogene Laherparepvec 100000000 PFU/1 ML Injection Suspension [IMLYGIC] DRUG

Talimogene laherparepvec, 1Bil is given intratumorally every 2 weeks according to tumor size

Also known as: TVEC, Imlygic

Talimogene laherparepvec, Nivolumab and Trabectedin

Nivolumab IV Soln 100 MG/10ML DRUG

NIVOLUMAB 240 mg IV over 30 min q 2 weeks

Also known as: Opdivo

Talimogene laherparepvec, Nivolumab and Trabectedin

Trabectedin 0.25 MG/1 VIAL Intravenous Powder for Solution DRUG

TRABECTEDIN 1.2 mg/m2 CIV over 24 hours q3 weeks

Also known as: Yondelis

Talimogene laherparepvec, Nivolumab and Trabectedin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or Female ≥ 18 years of age
• Pathologically confirmed diagnosis of locally advanced unresectable or metastatic sarcoma including desmoid tumor and chordoma
• Ability to understand the purposes and risks of the study and has signed and dated a written informed consent form approved by the Investigator's IRB/Ethics Committee
• Willingness to comply with all study procedures and availability for the duration of the study.
• Previously untreated or treated patient with measurable disease by RECIST v1.1, and at least, one accessible tumor for intratumoral injection of TALIMOGENE LAHERPAREPVEC
• ECOG performance status ≤ 1
• Life expectancy of at least 3 months
• Acceptable liver function: Bilirubin \<1.5 times upper limit of normal (ULN; except subjects with Gilbert Syndrome who must have a total bilirubin level \< 3.0 ULN); AST (SGOT), ALT (SGPT) and alk phos \< 2.5 x ULN (\< 5 x ULN if liver metastases present)
• Acceptable renal function: Creatinine \< 1.5 times ULN
• Acceptable hematologic status: ANC \>1500 cells/μL or greater; Platelet count \>100,000/μL or greater; Hemoglobin \> 9.0 g/dL or greater
• INR and PT \< 1.5 ULN unless taking anti-coagulation, in which case PT, INR and aPTT must be within therapeutic range of intended use of anticoagulants
• All women of childbearing potential must have a negative urine or serum pregnancy test within 72 hours of enrollment. If urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required; all subjects must agree to use highly effective means of contraception (surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 5 months for women and 7 months for men after the last dose.

You may not qualify if:

• Known active central nervous system (CNS) metastases. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids \>10 mg/day of prednisone or equivalent. The exception does not include carcinomatosus meningitis which is excluded regardless of clinical stability.
• History or evidence of active autoimmune disease that requires systemic treatment (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Evidence of clinically significant immunosuppression such as the following: - Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease. - concurrent opportunistic infection. - receiving systemic immunosuppressive therapy (\> 2 weeks) including oral steroid doses \> 10 mg/day of prednisone or equivalent within 7 days prior to study treatment.
• Active herpetic skin lesions or prior complications of HSV-1 infection (e.g., herpetic keratitis or encephalitis).
• Requires intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (e.g., acyclovir), other than intermittent topical use.
• Previous treatment with TALIMOGENE LAHERPAREPVEC or any other oncolytic virus.
• Received live vaccine within 28 days prior to study treatment.
• Prior immunosuppressive, chemotherapy, radiotherapy (in which the field encompassed a planned injection site), biological cancer therapy, or major surgery within 28 days prior to study treatment or has not recovered to CTCAE grade 1 or better from adverse event due to cancer therapy administered more than 28 days prior to study treatment. Adjuvant hormonal therapy is allowed if appropriate for planned study.
• Prior radiotherapy in which the field does not overlap the injection sites or nonimmunosuppressive targeted therapy within 14 days prior to study treatment or has not recovered to CTCAE grade 1 or better from adverse event due to cancer therapy administered more than 14 days prior to study treatment
• Currently receiving treatment with another investigational device or drug study, or \< 28 days since ending treatment with another investigational device or drug study(s).
• Other investigational procedures while participating in this study are excluded.
• Known to have acute or chronic active hepatitis B infection.
• Known to have acute or chronic active hepatitis C infection.
• Known to have human immunodeficiency virus (HIV) infection.
• History of other malignancy within the past 5 years with the following exceptions:

Sponsors & Collaborators

• Sarcoma Oncology Research Center, LLC: lead

Study Sites (1)

Sarcoma Oncology Center

Santa Monica, California, 90403, United States

RECRUITING

Related Publications (2)

• Gordon EM, Sankhala KK, Chawla N, Chawla SP. Trabectedin for Soft Tissue Sarcoma: Current Status and Future Perspectives. Adv Ther. 2016 Jul;33(7):1055-71. doi: 10.1007/s12325-016-0344-3. Epub 2016 May 27.

  PMID: 27234989 BACKGROUND

• Chawla SP, Sankhala KK, Ravicz J, Kang G, Liu S, Stumpf N, Leong B, Kim S, Arasheben S, Tseng WW, Gordon EM. Clinical experience with combination chemo-/immunotherapy using trabectedin and nivolumab for advanced soft tissue sarcoma. J Sarcoma Res. 2018; 2(1):1009.

  RESULT

MeSH Terms

Conditions

Sarcoma

Interventions

talimogene laherparepvec; Nivolumab; Trabectedin; Solutions

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations

Study Officials

• Sant P Chawla, MD

  Sarcoma Oncology Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Forty male and female patients with advanced sarcoma including desmoid tumor and chordoma will be treated with talimogene laherparepvec, nivolumab and trabectedin will be studied and evaluated for progression free survival at month 12.

Study Record Dates

• First Submitted: March 20, 2019
• First Posted: March 22, 2019
• Study Start: May 15, 2019
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): July 31, 2031
• Last Updated: February 24, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)