Ipilimumab With or Without Talimogene Laherparepvec in Unresected Melanoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01740297
First received: November 14, 2012
Last updated: March 28, 2016
Last verified: March 2016
  Purpose
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.

Condition Intervention Phase
Melanoma
Drug: Talimogene laherparepvec plus ipilimumab
Drug: Ipilimumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Safety and Tolerability [ Time Frame: 12 weeks following last subject enrolled ] [ Designated as safety issue: Yes ]
    Phase 1b: Determine the safety and tolerability of talimogene laherparepvec in combination with ipilimumab as assessed by incidence of dose-limiting toxicities (DLT) in subjects with previously untreated, unresected, stages IIIB to IV melanoma

  • Efficacy [ Time Frame: 24 months following last subject randomized ] [ Designated as safety issue: No ]
    Phase 2: Evaluate the efficacy as assessed by confirmed objective response rate (ORR) of treatment with talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone in subjects with unresected, stages IIIB to IV melanoma.


Secondary Outcome Measures:
  • Efficacy [ Time Frame: 24 months following last subject enrolled ] [ Designated as safety issue: No ]
    Phase 1b: Objective Response Rate (ORR)

  • Safety [ Time Frame: 24 months following last subject enrolled ] [ Designated as safety issue: Yes ]
    Phase 1b and Phase 2: Incidence of all AEs, grade 3 or greater AEs, Serious adverse events, events requiring discontinuation of study drug, local effects on tumor, clinically significant laboratory changes, and clinically significant changes in vital signs

  • Efficacy [ Time Frame: 24 months following last subject randomized ] [ Designated as safety issue: No ]
    Phase 2: Best Overall Response (BOR), Disease Control Rate (DCR), Deep Response Rate, Durable Response Rate (DRR), Duration of Response (DOR), Time to response (TTR), Progression free survival (PFS), resection rate, Overall Survival (OS), landmark OS by year


Enrollment: 217
Study Start Date: February 2013
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 1b and Phase 2 Arm 1
Talimogene laherparepvec plus ipilimumab
Drug: Talimogene laherparepvec plus ipilimumab
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.
Other Name: Talimogene laherparepvec plus Yervoy
Active Comparator: Phase 2 Arm 2
Ipilimumab
Drug: Ipilimumab
Ipilimumab administered intravenously on Day 1 of Week 1, 4, 7, and 10 for a total of 4 infusions.
Other Name: Yervoy

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01740297

  Hide Study Locations
Locations
United States, Arizona
Research Site
Tucson, Arizona, United States, 85724
United States, California
Research Site
Beverly Hills, California, United States, 90211
Research Site
Los Angeles, California, United States, 90025
Research Site
Los Angeles, California, United States, 90089-2211
Research Site
Los Angeles, California, United States, 90095
Research Site
San Francisco, California, United States, 94115
Research Site
Santa Rosa, California, United States, 95403
United States, Colorado
Research Site
Aurora, Colorado, United States, 80045
United States, Florida
Research Site
Jacksonville, Florida, United States, 32207
Research Site
Jacksonville, Florida, United States, 32224
Research Site
Lakeland, Florida, United States, 33805
Research Site
Miami, Florida, United States, 33140
United States, Illinois
Research Site
Chicago, Illinois, United States, 60612
United States, Indiana
Research Site
Indianapolis, Indiana, United States, 46260
Research Site
Indianapolis, Indiana, United States, 46202
United States, Iowa
Research Site
Iowa City, Iowa, United States, 52242
United States, Kentucky
Research Site
Louisville, Kentucky, United States, 40202
United States, Minnesota
Research Site
Minneapolis, Minnesota, United States, 55407
United States, Missouri
Research Site
St Louis, Missouri, United States, 63110
United States, New Jersey
Research Site
Morristown, New Jersey, United States, 07962
Research Site
New Brunswick, New Jersey, United States, 08903
United States, New York
Research Site
New York, New York, United States, 10032
Research Site
New York, New York, United States, 10029
United States, North Carolina
Research Site
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Research Site
Canton, Ohio, United States, 44718
Research Site
Cincinnati, Ohio, United States, 45267
United States, South Carolina
Research Site
Charleston, South Carolina, United States, 29425
United States, Tennessee
Research Site
Nashville, Tennessee, United States, 37232
United States, Texas
Research Site
Houston, Texas, United States, 77030
United States, Utah
Research Site
Salt Lake City, Utah, United States, 84112
United States, Virginia
Research Site
Richmond, Virginia, United States, 23298-0037
United States, Wisconsin
Research Site
Milwaukee, Wisconsin, United States, 53226
France
Research Site
Bordeaux, France, 33075
Research Site
Grenoble Cedex 9, France, 38043
Research Site
Lille, France, 59037
Research Site
Nantes Cedex 1, France, 44093
Research Site
Paris, France, 75010
Germany
Research Site
Göttingen, Germany, 37075
Research Site
Kiel, Germany, 24105
Research Site
Tübingen, Germany, 72076
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01740297     History of Changes
Other Study ID Numbers: 20110264 
Study First Received: November 14, 2012
Last Updated: March 28, 2016
Health Authority: United States: Food and Drug Administration
Germany: Paul-Ehrlich-Institut

Keywords provided by Amgen:
melanoma, talimogene laherparepvec, ipilimumab, metastatic melanoma, melanoma, immunotherapy, unresectable melanoma, oncolytic immunotherapy,

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 28, 2016