Single-arm Trial to Evaluate the Role of the Immune Response to Talimogene Laherparepvec in Unresected Melanoma

NCT02366195 | Completed Phase 2 Results

• 2 other identifiers: 201203252013-005552-15
• Study Type: interventional
• Target: 112
• Locations: 13 countries
• Sites: 42

Brief Summary

The study is a phase 2, multi centered, single arm study designed to evaluate the correlation between cluster of differentiation 8-positive (CD8+) cell density and objective response rate in adults with unresected stage IIIB to IVM1c melanoma. This study will also evaluate the safety and tolerability profile of talimogene laherparepvec.

Conditions

Unresected Stage IIIb to IVM1c Melanoma

Keywords

T-VEC; CD8+ cell density; objective response rate; unresected; Melanoma

Outcome Measures

Primary Outcomes (1)

• Odds Ratio of Baseline Intratumoral CD8+ Cell Density and Objective Response Rate

  A univariate logistic regression model was performed to evaluate baseline log2(CD8+ cell density) as a predictor of objective response. Response was assessed according to the modified version of the World Health Organization (WHO) response criteria. Objective response rate (ORR) was defined as the percentage of participants with a complete response (CR) or partial response (PR) according to the modified WHO criteria. The unadjusted odds ratio of log2(baseline intratumoral CD8+ cell density) for objective response rate is reported.

  Intratumoral CD8+ cell density: Baseline. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up at primary completion = 59 weeks (min 3 to max 116 weeks)

Secondary Outcomes (14)

• Odds Ratio of Baseline Intratumoral CD8+ Cell Density and Durable Response Rate

  Intratumoral CD8+ cell density: Baseline. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6)

• Hazards Ratio of Baseline Intratumoral CD8+ Cell Density and Duration of Response

  Intratumoral CD8+ cell density: Baseline. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 weeks)

• Correlation Between Baseline Intratumoral CD8+ Cell Density and Changes in Tumor Burden

  Intratumoral CD8+ cell density: Baseline; Tumor burden: First dose of study drug until primary completion date (26 June 2017) or end of follow-up; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 weeks)

• Odds Ratio of Change From Baseline Intratumoral CD8+ Cell Density and Objective Response Rate

  CD8+ cell density: Baseline & Week 6. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 weeks)

• Odds Ratio of Change From Baseline in Intratumoral CD8+ Cell Density and Durable Response Rate

  CD8+ cell density: Baseline & Week 6. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 weeks)

Study Arms (1)

Talimogene Laherparepvec

EXPERIMENTAL

Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. Participants were treated with talimogene laherparepvec until they achieved a complete response, all injectable tumors had disappeared, clinically significant (resulting in clinical deterioration or requiring change of therapy) disease progression beyond 6 months of treatment, per modified World Health Organization (WHO) response criteria, or intolerance of study treatment, whichever occurred first.

Drug: Talimogene Laherparepvec

Interventions

Talimogene Laherparepvec DRUG

The initial dose of talimogene laherparepvec is up to 4.0 mL of 10\^6 PFU/mL. Subsequent doses of talimogene laherparepvec are up to 4.0 mL of 10\^8 PFU/mL.

Also known as: IMLYGIC®

Talimogene Laherparepvec

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provided informed consent prior to initiation of any study-specific activities/procedures
• Subject with stage IIIB to IVM1c melanoma for whom surgery is not recommended
• Candidate for intralesional therapy
• Measurable disease with greatest diameter ≥ 10 mm
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ function

You may not qualify if:

• Clinically active cerebral metastases.
• Bone metastases
• Primary ocular or mucosal melanoma
• Active herpetic skin lesions or prior complications of herpes simplex virus type 1 (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
• 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
• Female subject of childbearing potential who is unwilling to use acceptable method(s) of effective contraception

Sponsors & Collaborators

• Amgen: lead

Study Sites (42)

Research Site

Salt Lake City, Utah, 84112, United States

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Salzburg, 5020, Austria

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Vienna, 1090, Austria

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Brussels, 1000, Belgium

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Brussels, 1200, Belgium

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Liège, 4000, Belgium

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Boulogne-Billancourt, 92100, France

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Marseille, 13385, France

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Nantes, 44093, France

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Paris, 75010, France

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Poitiers, 86021, France

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Essen, 45147, Germany

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Frankfurt am Main, 60590, Germany

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Hanover, 30625, Germany

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Heidelberg, 69120, Germany

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Athens, 11527, Greece

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Athens, 18547, Greece

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Heraklion - Crete, 71110, Greece

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Pátrai, 26504, Greece

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Thessaloniki, 54622, Greece

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Budapest, 1085, Hungary

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Budapest, 1122, Hungary

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Debrecen, 4032, Hungary

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Pécs, 7632, Hungary

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Szeged, 6720, Hungary

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Bergamo, 24127, Italy

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Milan, 20141, Italy

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Siena, 53100, Italy

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Amsterdam, 1081 HV, Netherlands

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Groningen, 9713 GZ, Netherlands

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Konin, 62-500, Poland

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Warsaw, 02-781, Poland

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Moscow, 115478, Russia

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Saint Petersburg, 197758, Russia

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Donostia / San Sebastian, Basque Country, 20014, Spain

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Badalona, Catalonia, 08916, Spain

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Barcelona, Catalonia, 08036, Spain

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Valencia, Valencia, 46014, Spain

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Madrid, 28009, Spain

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Madrid, 28041, Spain

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London, SE1 9RT, United Kingdom

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Metropolitan Borough of Wirral, CH63 4JY, United Kingdom

Location

Related Publications (1)

• Malvehy J, Samoylenko I, Schadendorf D, Gutzmer R, Grob JJ, Sacco JJ, Gorski KS, Anderson A, Pickett CA, Liu K, Gogas H. Talimogene laherparepvec upregulates immune-cell populations in non-injected lesions: findings from a phase II, multicenter, open-label study in patients with stage IIIB-IVM1c melanoma. J Immunother Cancer. 2021 Mar;9(3):e001621. doi: 10.1136/jitc-2020-001621.

  PMID: 33785610 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Melanoma

Interventions

talimogene laherparepvec

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2014
• First Posted: February 19, 2015
• Study Start: April 7, 2015
• Primary Completion: June 26, 2017
• Study Completion: December 25, 2020
• Last Updated: November 30, 2021
• Results First Posted: July 18, 2018

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.

Locations

FR (5); GR (5); US (1); HU (5); NL (2); DE (4); PL (2); ES (6); IT (3); BE (3); RU (2); GB (2); AU (2)