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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.
Full 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.
Enrollment
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Inclusion criteria
Individuals must meet all of the inclusion criteria in order to be eligible to participate in the study, as follows:
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:
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.
Primary purpose
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Interventional model
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40 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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