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

NCT03069378 | Active Not Recruiting Phase 2 Results FDA Drug

• 1 other identifier: 16-1534
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Sarcoma; Epithelioid Sarcoma; Cutaneous Angiosarcoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Best Objective Response Rate

  (complete response + partial response) RECIST 1.1. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  24 weeks

Study Arms (1)

Talimogene Laherparepvec (T-VEC) Administered with Pembrolizu

EXPERIMENTAL

Patients will initiate treatment with talimogene laherparepvec given intralesionally and pembrolizumab.

Drug: Talimogene Laherparepvec (T-VEC); Drug: Pembrolizumab

Interventions

Talimogene Laherparepvec (T-VEC) DRUG

Talimogene laherparepvec treatment will be given at Day 1 Week 1, and every 3 weeks thereafter .

Talimogene Laherparepvec (T-VEC) Administered with Pembrolizu

Pembrolizumab DRUG

Pembrolizumab will be given at Day 1 week 1 and every 3 weeks thereafter.

Talimogene Laherparepvec (T-VEC) Administered with Pembrolizu

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 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 inoperable sarcoma (metastatic/locally advanced cohort)
• For histology specific additional metastatic cohorts, patients must have undifferentiated pleomorphic sarcoma/myxofibrosarcoma, epithelioid sarcoma or cutaneous angiosarcoma.
• Subjects must have at least 1 injectable cutaneous, subcutaneous (superficial or deep) 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 with locally advanced/metastatic sarcoma must have at least one prior line of systemic therapy (e.g. chemotherapy, immunotherapy, targeted or biological therapy). An exception to this criterion will be made for patients with sarcoma histological subtypes for which there is no known standard systemic therapy (e.g., epithelioid sarcoma). Treatment naive patients may be enrolled if they have refused standard systemic treatment. Prior adjuvant therapy will not count provided it was completed more than 6 months previously
• Adequate performance status: ECOG 0 or 1/KPS 100-70%
• Adequate organ function determined within 3 weeks of treatment initiation, defined as follows:
• I. Hemoglobin ≥ 8.0 g/dl
• II. Absolute neutrophil count ≥ 1,000/mm\^3 (1.0 x 10\^9/L)
• III. Platelet count ≥ 75,000/mm3 (75 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

You may not qualify if:

• 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 or live-attenuated vaccine within 30 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 pembrolizumab. (Note: Women not of childbearing potential are defined as: Any female who is post-menopausal \[age \> 55 years with cessation of menses for 12 or more months or less than 55 years but not spontaneous menses for at least 2 years or less than 55 years and spontaneous menses within the past 1 year, but currently amenorrhoeic(e.g., spontaneous or secondary to hysterectomy), and with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating hormone levels \> 40 IU/L) or postmenopausal estradiol levels (\< 5 ng/dL) or according to the definition of "postmenopausal range" for the laboratory involved\] or who have had a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy)

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Amgen: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (5)

Enable Medicine (Specimen Analysis Only)

Menlo Park, California, 94025, United States

Location

Stanford University Medical Center

Stanford, California, 94305-5408, United States

Location

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MD Anderson Cancer Center (Data Analysis Only)

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Goff PH, Riolobos L, LaFleur BJ, Spraker MB, Seo YD, Smythe KS, Campbell JS, Pierce RH, Zhang Y, He Q, Kim EY, Schaub SK, Kane GM, Mantilla JG, Chen EY, Ricciotti R, Thompson MJ, Cranmer LD, Wagner MJ, Loggers ET, Jones RL, Murphy E, Blumenschein WM, McClanahan TK, Earls J, Flanagan KC, LaFranzo NA, Kim TS, Pollack SM. Neoadjuvant Therapy Induces a Potent Immune Response to Sarcoma, Dominated by Myeloid and B Cells. Clin Cancer Res. 2022 Apr 14;28(8):1701-1711. doi: 10.1158/1078-0432.CCR-21-4239.

  PMID: 35115306 DERIVED

• Kelly CM, Antonescu CR, Bowler T, Munhoz R, Chi P, Dickson MA, Gounder MM, Keohan ML, Movva S, Dholakia R, Ahmad H, Biniakewitz M, Condy M, Phelan H, Callahan M, Wong P, Singer S, Ariyan C, Bartlett EK, Crago A, Yoon S, Hwang S, Erinjeri JP, Qin LX, Tap WD, D'Angelo SP. Objective Response Rate Among Patients With Locally Advanced or Metastatic Sarcoma Treated With Talimogene Laherparepvec in Combination With Pembrolizumab: A Phase 2 Clinical Trial. JAMA Oncol. 2020 Mar 1;6(3):402-408. doi: 10.1001/jamaoncol.2019.6152.

  PMID: 31971541 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Sarcoma; Neoplasm Metastasis

Interventions

talimogene laherparepvec; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Ciara Kelly, MD
• Organization: Memorial Sloan Kettering Cancer Center

Kellyc1@mskcc.org

646-888-4312

Study Officials

• Ciara Kelly, MBBCh BAO

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: This is a single-center, phase II study to evaluate the efficacy of the oncolytic herpes virus talimogene laherparepvec, given in combination with pembrolizumab for patients with metastatic and/or locally advanced sarcomas.

Study Record Dates

• First Submitted: February 27, 2017
• First Posted: March 3, 2017
• Study Start: March 3, 2017
• Primary Completion: July 22, 2025
• Study Completion: March 1, 2026
• Last Updated: October 29, 2025
• Results First Posted: October 29, 2025

Record last verified: 2025-07

Locations

US (5)