Clinical Trials /

A Study of Talimogene Laherparepvec (T-VEC) in Combination With Pembrolizumab in Patients With Metastatic and/or Locally Advanced Sarcoma

NCT03069378

Description:

The purpose of this study is to determine how well the combination of therapy of talimogene laherparepvec (T-VEC) and pembrolizumab works in the treatment of patients with sarcoma.

Related Conditions:
  • Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Talimogene Laherparepvec (T-VEC) in Combination With Pembrolizumab in Patients With Metastatic and/or Locally Advanced Sarcoma
  • Official Title: A Phase II Study of Talimogene Laherparepvec (T-VEC) Administered Concurrently With the Anti-PD1 Monoclonal Antibody Pembrolizumab in Patients With Metastatic and/or Locally Advanced Sarcoma

Clinical Trial IDs

  • ORG STUDY ID: 16-1534
  • NCT ID: NCT03069378

Conditions

  • Sarcoma

Interventions

DrugSynonymsArms
Talimogene Laherparepvec (T-VEC)Talimogene Laherparepvec (T-VEC) Administered with Pembrolizu
PembrolizumabTalimogene Laherparepvec (T-VEC) Administered with Pembrolizu

Purpose

The purpose of this study is to determine how well the combination of therapy of talimogene laherparepvec (T-VEC) and pembrolizumab works in the treatment of patients with sarcoma.

Trial Arms

NameTypeDescriptionInterventions
Talimogene Laherparepvec (T-VEC) Administered with PembrolizuExperimentalPatients will initiate treatment with talimogene laherparepvec given intralesionally and pembrolizumab.
  • Talimogene Laherparepvec (T-VEC)
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female age ≥ 18 years at the time of informed consent

          -  Be willing and able to provide written informed consent/assent for the trial

          -  Be willing to comply with treatment protocol

          -  Subjects must have a histologically confirmed metastatic and/or locally advanced
             sarcoma

          -  Subjects must have at least 1 injectable cutaneous, subcutaneous soft tissue or nodal
             lesion ≥ 10 mm in longest diameter. Of note, bone lesions are not eligible for
             injection unless there is a soft tissue component that is amenable to injection.
             Injectable lesions must not be chosen from a previously irradiated field unless there
             has been radiographically and/or pathologically documented tumor progression in that
             lesion prior to enrollment

          -  Subjects must have at least one prior line of systemic therapy (e.g. chemotherapy,
             immunotherapy, targeted or biological therapy) for their sarcoma. Prior adjuvant
             therapy will not count provided it was completed more than 6 months previously

          -  Subjects must have measurable disease (at least one target lesion) as defined by
             RECIST 1.1. Target lesions must not be chosen from a previously irradiated field
             unless there has been radiographically and/or pathologically documented tumor
             progression in that lesion prior to enrollment

          -  Adequate performance status: ECOG 0 or 1/KPS 100-70%

          -  Adequate organ function determined within 10 days of treatment initiation, defined as
             follows:

          -  I. Hemoglobin ≥ 8.0 g/dl (without need for hematopoietic growth factor or transfusion
             support)

          -  II. Absolute neutrophil count ≥ 1,500/mm3 (1.5 x 109/L)

          -  III. Platelet count ≥ 100,000/mm3 (100 x 109/L)

          -  IV. Serum bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ ULN for a subject with total
             bilirubin level > 1.5 x ULN

          -  V. Aspartate aminotransferase (AST) ≤ 2.5 x ULN OR ≤ 5 x ULN for subjects with liver
             metastases

          -  VI. Alanine aminotransferase (ALT) ≤ 2.5 x ULN OR ≤ 5 x ULN for subjects with liver
             metastases

          -  VII. Alkaline Phosphatase < 5 x ULN

          -  VIII. Albumin ≥2.5mg/dL

          -  IX. Serum creatinine ≤ 1.5 x ULN or a measured or calculateda* creatinine clearance ≥
             60mL/min for subject with creatinine levels > 1.5 x institutional ULN (Note:
             Creatinine clearance need not be determined if the baseline serum creatinine is
             within normal limits. GFR can also be used in place of creatinine or CrCl) X.
             International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless
             subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic
             range of intended use of anticoagulants XI. Activated partial thromboplastin time
             (aPTT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT
             and PTT is within therapeutic range of intended use of anticoagulants

             *aCreatinine clearance should be calculated per institutional standard

          -  Female subject of childbearing potential should have a negative serum pregnancy
             testing at screening visit and within 72 hours prior to the first dose of study
             medication

        Exclusion Criteria:

          -  Uncontrolled intercurrent illness including active infection requiring systemic
             therapy or symptomatic congestive heart failure within 6 months

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. 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 for at least 7 days prior to trial treatment. This
             exception does not include carcinomatous meningitis which is excluded regardless of
             clinical stability

          -  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 enrollment.
                  However, in the setting of non-immune mediated indications for use,
                  chronic/active low dose steroid use may be permitted at the discretion of the
                  principal investigator

          -  Known history of human immunodeficiency virus (HIV) disease

          -  History or evidence of symptomatic autoimmune disease (e.g., pneumonitis,
             glomerulonephritis, vasculitis, or other), or history of active autoimmune disease
             that has required systemic treatment (i.e., use of corticosteroids, immunosuppressive
             drugs or biological agents used for treatment of autoimmune diseases) in past 2 years
             prior to enrollment. Replacement therapy (e.g., thyroxine for hypothyroidism, insulin
             for diabetes or physiologic corticosteroid replacement therapy for adrenal or
             pituitary insufficiency) is not considered a form of systemic treatment for
             autoimmune disease

          -  Active herpetic skin lesions or prior complications of herpetic infection

          -  Require intermittent or chronic treatment with an intravenous or oral antiherpetic
             drug (e.g., acyclovir), other than intermittent topical use

          -  Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected)

          -  Received live vaccine within 28 days prior to enrollment. Note: Seasonal influenza
             vaccines for injection are generally inactivated flu vaccines and are allowed;
             however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines,
             and are not allowed

          -  Has a known history of active TB (Bacillus Tuberculosis)

          -  Female subject is pregnant or breast-feeding, or planning to become pregnant or male
             subject is planning to father a child within the projected duration of the trial,
             starting with the pre-screening or screening visit, during study treatment and
             through 3 months after the last dose of talimogene laherparepvec or 4 months after
             the last dose of pembrolizumab, whichever is later

          -  Male and female subjects of childbearing potential who are unwilling to use
             acceptable method(s) of effective contraception during study treatment and through 3
             months after the last dose of talimogene laherparepvec and 4 months after the last
             dose of pemrolizumab. (Note: Women not of childbearing potential are defined as: Any
             female who is post-menopausal [age > 55 years with cessation of menses for 12 or more
             months or less than 55 years but not spontaneous menses for at least 2 years or less
             than 55 years and spontaneous menses within the past 1 year, but currently
             amenorrheic (e.g., spontaneous or secondary to hysterectomy), and with postmenopausal
             gonadotropin levels (luteinizing hormone and follicle-stimulating hormone levels > 40
             IU/L) or postmenopausal estradiol levels (< 5 ng/dL) or according to the definition
             of "postmenopausal range" for the laboratory involved] or who have had a
             hysterectomy, bilateral salpingectomy, or bilateral oophorectomy)

          -  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 30days after treatment with talimogene laherparepvec

          -  Subject who is 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 children under the age of 1 year, during talimogene laherparepvec treatment
             and through 30 days after the last dose of talimogene laherparepvec

          -  Known previous history of sensitivity to talimogene laherparepvec or any of its
             components to be administered during dosing (e.g. sorbitol, myo-inositol)

          -  Hypersensitivity to pembrolizumab or any of its excipients

          -  Prior therapy with talimogene laherparepvec, tumor vaccine

          -  Prior chemotherapy, radiotherapy, biological cancer therapy, targeted small molecule
             therapy or major surgery within 21 days prior to study Day 1 or who has not recovered
             (i.e., to CTCAE ≤ grade 1 or at baseline) from adverse events due to previously
             administered therapy. Note: Subjects with ≤ grade 2 neuropathy and alopecia are an
             exception to this criterion and may qualify for the study. Note: If subject received
             major surgery, they must have recovered adequately from the toxicity and/or
             complications from the intervention prior to starting therapy

          -  Is currently participating and receiving study therapy with another investigational
             device or study drug or has participated in a study of an investigational agent and
             received study therapy or used an investigational device within 4 weeks of the first
             dose of treatment

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial

          -  The presence of any other concurrent active malignancy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:best objective response rate
Time Frame:24 weeks
Safety Issue:
Description:(complete response + partial response) RECIST 1.1

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Metastatic
  • Locally Advanced
  • Talimogene Laherparepvec (T-VEC)
  • Pembrolizumab
  • 16-1534

Last Updated

April 19, 2017