Clinical Trials /

Talimogene Laherparepvec, Nivolumab and Trabectedin for Sarcoma

NCT03886311

Description:

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.

Related Conditions:
  • Chordoma
  • Desmoid-Type Fibromatosis
  • Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Talimogene Laherparepvec, Nivolumab and Trabectedin for Sarcoma
  • Official Title: The TNT Protocol: A Phase 2 Study Using Talimogene Laherparepvec,Nivolumab and Trabectedin as First, Second/Third Line Therapy for Advanced Sarcoma, Including Desmoid Tumor and Chordoma

Clinical Trial IDs

  • ORG STUDY ID: SOC-1882
  • NCT ID: NCT03886311

Conditions

  • Sarcoma

Interventions

DrugSynonymsArms
Talimogene Laherparepvec 100000000 PFU/1 ML Injection Suspension [IMLYGIC]TVEC, ImlygicTalimogene laherparepvec, Nivolumab and Trabectedin
Nivolumab IV Soln 100 MG/10MLOpdivoTalimogene laherparepvec, Nivolumab and Trabectedin
Trabectedin 0.25 MG/1 VIAL Intravenous Powder for SolutionYondelisTalimogene laherparepvec, Nivolumab and Trabectedin

Purpose

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.

Detailed Description

      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. The
      primary objective is to determine progression-free survival (PFS) at month 12. The secondary
      objectives are (1) To evaluate the best overall response (BOR) and duration of response (DOR)
      by RECIST v1.1 via CT scan or MRI at 6,12,18, and 24 weeks post treatment, (2) To determine
      progression-free survival rate (PFS) at 6 and 9 months, (3) To determine overall survival
      rate at 6, 9, and 12 months, (4) To determine the incidence of conversion of an unresectable
      tumor to a resectable tumor, and (5) To evaluate the incidence of adverse events related to
      TALIMOGENE LAHERPAREPVEC in combination with nivolumab and trabectedin. The exploraratory
      objective is to correlate response with immune cell trafficking in the tumor microenvironment
      (TME) of resected tumors.

      The primary endpoint is Progression free survival at month 12. The secondary endpoints are:
      1) Best overall response (BOR) and duration of response (DOR) by RECIST v1.1 via CT scan or
      MRI at 6,12,18 and 24 weeks post treatment, 2) PFS rate at 6 and 9 months

      • Overall survival rate at 6, 9, and 12 months, 3) Incidence of conversion of an unresectable
      tumor to a resectable tumor, 4) Incidence of adverse events related to TALIMOGENE
      LAHERPAREPVEC in combination with nivolumab and trabectedin. The exploratory endpoint is
      correlation of response with immune cell trafficking in the tumor microenvironment of
      resected tumors.

      Forty male and female subjects > 18 years of age, of any ethnicity, with advanced sarcoma,
      including desmoid tumor and chordoma will be treated.
    

Trial Arms

NameTypeDescriptionInterventions
Talimogene laherparepvec, Nivolumab and TrabectedinExperimentalThis 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.
  • Talimogene Laherparepvec 100000000 PFU/1 ML Injection Suspension [IMLYGIC]
  • Nivolumab IV Soln 100 MG/10ML
  • Trabectedin 0.25 MG/1 VIAL Intravenous Powder for Solution

Eligibility Criteria

        Inclusion Criteria:

          -  Individuals must meet all of the inclusion criteria in order to be eligible to
             participate in the study, as follows:

               -  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.

        Exclusion Criteria:

          -  All individuals meeting any of the exclusion criteria at baseline will be excluded
             from study participation, as follows:

               -  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:

                    -  Adequately treated non melanoma skin cancer without evidence of disease at
                       the time of enrollment;

                    -  Adequately treated cervical carcinoma in situ without evidence of disease at
                       the time of enrollment;

                    -  Adequately treated breast ductal carcinoma in situ without evidence of
                       disease at the time of enrollment;

                    -  Prostatic intraepithelial neoplasia without evidence of prostate cancer at
                       the time of enrollment.

               -  Subject has known sensitivity to TALIMOGENE LAHERPAREPVEC, NIVOLUMAB or
                  TRABECTEDIN or any of its components to be administered during dosing.

               -  Female subject is pregnant or breast-feeding or planning to become pregnant
                  during study treatment and through 3 months after the last dose of TALIMOGENE
                  LAHERPAREPVEC, NIVOLUMAB or TRABECTEDIN.

               -  Female subject of childbearing potential who is unwilling to use acceptable
                  method(s) of effective contraception during study treatment and through 3 months
                  after the last dose of TALIMOGENE LAHERPAREPVEC, NIVOLUMAB or TRABECTEDIN.

               -  Sexually active subjects and their partners unwilling to use male or female latex
                  condom to avoid potential viral transmission during sexual contact while on
                  treatment and within 30 days after treatment with TALIMOGENE LAHERPAREPVEC.

               -  Subjects who are unwilling to minimize exposure with his/her blood or other body
                  fluids to individuals who are at higher risks for HSV-1 induced complications
                  such as immunosuppressed individuals, individuals known to have HIV infection,
                  pregnant women, or infants under the age of 3 months, during TALIMOGENE
                  LAHERPAREPVEC treatment and through 30 days after the last dose of TALIMOGENE
                  LAHERPAREPVEC.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival
Time Frame:12 months
Safety Issue:
Description:Progression free survival at month 12

Secondary Outcome Measures

Measure:Best overall response and duration of response
Time Frame:12 months
Safety Issue:
Description:• Best overall response (BOR) and duration of response (DOR) by RECIST v1.1 via CT scan or MRI at 6,12,18 and 24 weeks post treatment
Measure:Progression free survival rate
Time Frame:Nine months
Safety Issue:
Description:Prgoression Free Survival rate at 6 and 9 months
Measure:)verall survival rate
Time Frame:12 months
Safety Issue:
Description:Overall survival rate at 6, 9, and 12 months
Measure:Convesion to resectable tumor
Time Frame:12 months
Safety Issue:
Description:Incidence of conversion of an unresectable tumor to a resectable tumor
Measure:Incidence of adverse events
Time Frame:12 months
Safety Issue:
Description:• Incidence of adverse events related to TALIMOGENE LAHERPAREPVEC in combination with nivolumab and trabectedin

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sarcoma Oncology Research Center, LLC

Trial Keywords

  • marine derived alkaloid
  • PD1 inhibitor
  • CTLA4 inhibitor

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