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SarcomaPhase 2TNTNCT03886311

Talimogene Laherparepvec, Nivolumab and Trabectedin for Sarcoma

A Phase 2 study testing Talimogene Laherparepvec 100000000 PFU/1 ML Injection Suspension [IMLYGIC], Nivolumab IV Soln 100 MG/10ML and Trabectedin 0.25 MG/1 VIAL Intravenous Powder for Solution in people with Sarcoma, run by Sarcoma Oncology Research Center, LLC at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Sarcoma
What is being tested?
Talimogene Laherparepvec 100000000 PFU/1 ML Injection Suspension [IMLYGIC], Nivolumab IV Soln 100 MG/10ML and Trabectedin 0.25 MG/1 VIAL Intravenous Powder for Solution
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
200 participants
Where
1 siteUnited States
Study dates
15 May 2019to 31 Jul 2031
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site, 1 recruiting

  • Sarcoma Oncology Center

    Santa Monica, California, 90403

    Victoria Chua, 310-552-9999, vchua@sarcomaoncology.com

    Sant P Chawla, MD, 310-552-9999, santchawla@sarcomaoncology.com

    Recruiting

Other trials in United States

About this study

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

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.

Read the 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.

Conditions
Sarcoma
Being tested
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
Keywords
marine derived alkaloid, PD1 inhibitor, CTLA4 inhibitor
Medical subject headings
Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    Also called TVEC, Imlygic

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

  • Nivolumab IV Soln 100 MG/10MLDrug

    Also called Opdivo

    NIVOLUMAB 240 mg IV over 30 min q 2 weeks

  • Trabectedin 0.25 MG/1 VIAL Intravenous Powder for SolutionDrug

    Also called Yondelis

    TRABECTEDIN 1.2 mg/m2 CIV over 24 hours q3 weeks

Study groups in NCT03886311
Study groupRoleWhat they receive
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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression free survival

    Progression free survival at month 12

    Measured: 12 months

Secondary outcomes (5)

  1. Best overall response and duration of response

    • 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

    Measured: 12 months

  2. Progression free survival rate

    Prgoression Free Survival rate at 6 and 9 months

    Measured: Nine months

  3. )verall survival rate

    Overall survival rate at 6, 9, and 12 months

    Measured: 12 months

  4. Convesion to resectable tumor

    Incidence of conversion of an unresectable tumor to a resectable tumor

    Measured: 12 months

  5. Incidence of adverse events

    • Incidence of adverse events related to TALIMOGENE LAHERPAREPVEC in combination with nivolumab and trabectedin

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Mar 2019
  2. Study start15 May 2019
  3. Primary completion31 Dec 2030 (estimated)
  4. Study completion31 Jul 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
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.
Masking
None (open label)
Enrolment
200 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03886311
Sponsor's protocol ID
SOC-1882
Acronym
TNT
Status last verified
Feb 2025
First submitted
20 Mar 2019
Last updated
24 Feb 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 27234989

  • 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.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Talimogene Laherparepvec 100000000 PFU/1 ML Injection Suspension [IMLYGIC], Nivolumab IV Soln 100 MG/10ML and Trabectedin 0.25 MG/1 VIAL Intravenous Powder for Solution in people with Sarcoma, run by Sarcoma Oncology Research Center, LLC at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 24 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03886311, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2025.

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