Overview

This trial is active, not recruiting.

Condition melanoma
Treatments talimogene laherparepvec plus ipilimumab, ipilimumab
Phase phase 1/phase 2
Target CTLA-4
Sponsor Amgen
Start date February 2013
End date August 2016
Trial size 217 participants
Trial identifier NCT01740297, 20110264

Summary

Phase 1b of the study will evaluate the safety of talimogene laherparepvec in combination with ipilimumab. Phase 2 is a randomized study that will evaluate the safety and efficacy of talimogene laherparepvec in combination with ipilimumab versus ipilumumab alone. Talimogene laherparepvec will be administered by intratumor injection, and ipilimumab will be administered by intravenous infusion for a total of 4 infusions. Subjects will be treated with talimogene laherparepvec until complete response, all injectable tumors have disappeared, disease progression per a modified Immune-Related Response Criteria (irRC), or intolerance of study treatment.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Talimogene laherparepvec plus ipilimumab
talimogene laherparepvec plus ipilimumab Talimogene laherparepvec plus Yervoy
Talimogene laherparepvec administered by intratumoral injection on Day 1 of Week 1, Day 1 of Week 4, then every two weeks thereafter. Ipilimumab administered intravenously on Day 1 of Week 6, Week 9, Week 12, and Week 15 for a total of 4 infusions. Subjects will be treated wtih talimogene laherparepvec until complete response, all injectable tumors have disappeared, confirmed disease progression per the modified irRC, or intolerance of study treatment, whichever occurs first.
(Active Comparator)
Ipilimumab
ipilimumab Yervoy
Ipilimumab administered intravenously on Day 1 of Week 1, 4, 7, and 10 for a total of 4 infusions.

Primary Outcomes

Measure
Safety and Tolerability
time frame: 12 weeks following last subject enrolled
Efficacy
time frame: 24 months following last subject randomized

Secondary Outcomes

Measure
Efficacy
time frame: 24 months following last subject enrolled
Safety
time frame: 24 months following last subject enrolled
Efficacy
time frame: 24 months following last subject randomized

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Histologically confirmed diagnosis of malignant melanoma. - Stage IIIB, IIIC, IVM1a, IVM1b, or IVM1c disease that is not suitable for surgical resection - Phase1: Treatment naïve: Must not have received any prior systemic anticancer treatment consisting of chemotherapy, immunotherapy, or targeted therapy for unresected stage IIIB to IV melanoma. - Phase 2: Either treatment naïve or received only one line of systemic anticancer therapy if BRAF wild-type or up to two lines of systemic anticancer therapy including one BRAF inhibitor-containing regimen if BRAF mutant. Treatments given in an adjuvant setting (eg, interferon, radiotherapy, isolated limb perfusion, or investigational agents) are not considered as prior lines of therapy. No prior talimogene laherparepvec, other oncolytic virus therapies, or tumor vaccines are allowed, even if given in the adjuvant setting. - Phase 2: Subjects treated with prior ipilimumab must have had PR, CR, or at least 6 months of stable disease followed by disease progression. - Phase 2: Subjects previously treated with anti-PD1 or anti-CTLA-4 antibodies must not have discontinued therapy due to any treatment-related adverse events including immune-related adverse events. Prior treatment-related adverse events should also be fully resolved and not requiring treatment for at least 28 days prior to randomization. - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - Adequate hematologic, hepatic, renal, and coagulation functions Exclusion Criteria: - Primary uveal or mucosal melanoma - History or evidence of melanoma associated with immunodeficiency states (eg, hereditary immune deficiency, organ transplant, or leukemia) - Phase 1b: History or evidence of central nervous system (CNS) metastases - Phase 2: Clinically active cerebral melanoma metastases. Subjects with up to 3 cerebral metastases, and neurological performance status of 0 may be enrolled,provided that all lesions have been adequately treated with stereotactic radiation therapy, craniotomy, or Gamma knife therapy, with no evidence of progression, and have not required steroids, for at least 2 months prior to enrollment. - History or evidence of symptomatic autoimmune disease (such as pneumonitis, glomerulonephritis, vasculitis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, scleroderma, or other), or history of autoimmune disease that required systemic treatment (ie, use of corticosteroids, immunosuppressive drugs or biological agents used for treatment of autoimmune diseases) in past 2 months prior to enrollment. Replacement therapy (eg, thyroxine for hypothyroidism, insulin for diabetes mellitus) is not considered a form of systemic treatment for autoimmune disease. - History of or plan for splenectomy or splenic irradiation - Active herpetic skin lesions or prior complications of HSV-1 infection (eg, herpetic keratitis or encephalitis). - Requires intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use - Known human immunodeficiency virus (HIV) disease - Known acute or chronic hepatitis B or hepatitis C infection - Phase 1b: Prior talimogene laherparepvec, ipilimumab, other Cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) inhibitors, programmed death-1 (PD-1) inhibitors, or tumor vaccine - Phase 2: Prior talimogene laherparepvec, other oncolytic virus therapies, or tumor vaccines - Currently receiving or less than 28 days since ending systemic anticancer treatment for unresected stage IIIB to IV melanoma

Additional Information

Official title Phase 1b/2, Multicenter, Open-label Trial to Evaluate the Safety and Efficacy of Talimogene Laherparepvec and Ipilimumab Compared to Ipilimumab Alone in Subjects With Unresected, Stage IIIB-IV Melanoma
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Amgen.