Ipilimumab With or Without Talimogene Laherparepvec in Unresectable Melanoma - Full Text View

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 Previously Untreated, Unresectable, Stage IIIb-IV Melanoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Ipilimumab

U.S. FDA Resources

Further study details as provided by Amgen:

Primary Outcome Measures:

Safety and Tolerability [ Time Frame: 24 months 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)
Efficacy [ Time Frame: 24 months following last subject randomized ] [ Designated as safety issue: No ]
Phase 2: Estimate the efficacy of talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone as assessed by overall survival (OS)

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: Objective Response Rate, Time to Response (TTR), Duration of Response (DOR), Progression free survival (PFS), resection rate, 1-year survival rate, 2-year survival rate

Estimated Enrollment:	149
Study Start Date:	February 2013
Estimated Study Completion Date:	July 2017
Estimated Primary Completion Date:	July 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 respone, all injectable tumors have disappeared, 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

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 respone, all injectable tumors have disappeared, 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
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
Treatment naïve: Must not have received any prior systemic anticancer treatment consisting of chemotherapy, immunotherapy, or targeted therapy for unresectable stage IIIb to IV melanoma.
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)
History or evidence of central nervous system (CNS) metastases
History or evidence of gastrointestinal inflammatory bowel disease (ulcerative colitis or Crohn disease) or other symptomatic autoimmune disease
History of or plan for splenectomy or splenic irradiation
Active herpetic skin lesions
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

Contacts and Locations

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

Contacts

Contact: Amgen Call Center

866-572-6436

Locations

United States, California
Research Site	Recruiting
Los Angeles, California, United States, 90025
Research Site	Recruiting
Los Angeles, California, United States, 90024
Research Site	Recruiting
San Francisco, California, United States, 94115
United States, Illinois
Research Site	Recruiting
Chicago, Illinois, United States, 60612
United States, Iowa
Research Site	Recruiting
Iowa City, Iowa, United States, 52242
United States, New York
Research Site	Recruiting
New York, New York, United States, 10128
United States, Tennessee
Research Site	Recruiting
Nashville, Tennessee, United States, 37232
United States, Utah
Research Site	Recruiting
Salt Lake City, Utah, United States, 84112

Sponsors and Collaborators

Amgen

Investigators

Study Director:

MD

Amgen

More Information

Additional Information:

AmgenTrials clinical trials website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Amgen
ClinicalTrials.gov Identifier:	NCT01740297 History of Changes
Other Study ID Numbers:	20110264
Study First Received:	November 14, 2012
Last Updated:	May 14, 2013
Health Authority:	United States: Food and Drug Administration

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
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 22, 2013