Combination therapy for advanced sarcoma using three different treatments

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.