Avelumab in patients with previously treated metastatic melanoma: Phase 1b results from the JAVELIN Solid Tumor trial

Ulrich Keilholz, Janice M. Mehnert, Sebastian Bauer, Hugues Bourgeois, Manish R. Patel, Donald Gravenor, John J. Nemunaitis, Matthew Taylor, Lucjan Wyrwicz, Keun Wook Lee, Vijay Kasturi, Kevin Chin, Anja Von Heydebreck, James L. Gulley

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    Abstract

    Background: We report phase 1b data from patients enrolled in the JAVELIN Solid Tumor clinical trial (NCT01772004) with unresectable stage IIIC or IV melanoma that had progressed after ≥1 line of therapy for metastatic disease. Patients and methods: Patients received avelumab (10 mg/kg) - a human anti-PD-L1 antibody. Assessments included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Results: As of December 31, 2016, 51 patients were treated and followed for a median of 24.2 months (range, 16.1-31.5). Most patients had cutaneous (n = 28 [54.9%]) or ocular (n = 16 [31.4%]) melanoma and had received a median of 2 prior lines of therapy (range, 0-4), including ipilimumab (n = 26 [51.0%]). The confirmed ORR was 21.6% (95% CI, 11.3-35.3; complete response, 7.8%; partial response, 13.7%). The median duration of response was not estimable (95% CI, 2.6 months-not estimable). Median PFS and OS were 3.1 months (95% CI, 1.4-6.3) and 17.2 months (95% CI, 6.6-not estimable), respectively. Subgroup analyses suggested meaningful clinical activity (ORR [95% CI]) in patients with non-ocular melanoma (31.4% [16.9-49.3]), PD-L1-positive tumors (42.1% [20.3-66.5]), or prior ipilimumab therapy (30.8% [14.3-51.8]). Thirty-nine patients (76.5%) had a treatment-related adverse event (TRAE), most commonly infusion-related reaction (29.4%), fatigue (17.6%), and chills (11.8%); 4 patients (7.8%) had a grade 3 TRAE. Five patients (9.8%) had an immune-related TRAE (all were grade 1/2). No grade 4 TRAEs or treatment-related deaths were reported. Conclusion: Avelumab showed durable responses, promising survival outcomes, and an acceptable safety profile in patients with previously treated metastatic melanoma. Trial registration: ClinicalTrials.gov identifier: NCT01772004.

    Original languageEnglish (US)
    Article number12
    JournalJournal for ImmunoTherapy of Cancer
    Volume7
    Issue number1
    DOIs
    StatePublished - Jan 16 2019

    Fingerprint

    Melanoma
    Neoplasms
    Therapeutics
    Disease-Free Survival
    Survival
    avelumab
    Safety
    Chills
    Fatigue
    Clinical Trials
    Skin
    Antibodies

    Keywords

    • Avelumab
    • Cutaneous melanoma
    • Immune checkpoint inhibitor
    • Ocular melanoma
    • PD-L1

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology
    • Molecular Medicine
    • Oncology
    • Pharmacology
    • Cancer Research

    Cite this

    Avelumab in patients with previously treated metastatic melanoma : Phase 1b results from the JAVELIN Solid Tumor trial. / Keilholz, Ulrich; Mehnert, Janice M.; Bauer, Sebastian; Bourgeois, Hugues; Patel, Manish R.; Gravenor, Donald; Nemunaitis, John J.; Taylor, Matthew; Wyrwicz, Lucjan; Lee, Keun Wook; Kasturi, Vijay; Chin, Kevin; Von Heydebreck, Anja; Gulley, James L.

    In: Journal for ImmunoTherapy of Cancer, Vol. 7, No. 1, 12, 16.01.2019.

    Research output: Contribution to journalArticle

    Keilholz, U, Mehnert, JM, Bauer, S, Bourgeois, H, Patel, MR, Gravenor, D, Nemunaitis, JJ, Taylor, M, Wyrwicz, L, Lee, KW, Kasturi, V, Chin, K, Von Heydebreck, A & Gulley, JL 2019, 'Avelumab in patients with previously treated metastatic melanoma: Phase 1b results from the JAVELIN Solid Tumor trial', Journal for ImmunoTherapy of Cancer, vol. 7, no. 1, 12. https://doi.org/10.1186/s40425-018-0459-y
    Keilholz, Ulrich ; Mehnert, Janice M. ; Bauer, Sebastian ; Bourgeois, Hugues ; Patel, Manish R. ; Gravenor, Donald ; Nemunaitis, John J. ; Taylor, Matthew ; Wyrwicz, Lucjan ; Lee, Keun Wook ; Kasturi, Vijay ; Chin, Kevin ; Von Heydebreck, Anja ; Gulley, James L. / Avelumab in patients with previously treated metastatic melanoma : Phase 1b results from the JAVELIN Solid Tumor trial. In: Journal for ImmunoTherapy of Cancer. 2019 ; Vol. 7, No. 1.
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    abstract = "Background: We report phase 1b data from patients enrolled in the JAVELIN Solid Tumor clinical trial (NCT01772004) with unresectable stage IIIC or IV melanoma that had progressed after ≥1 line of therapy for metastatic disease. Patients and methods: Patients received avelumab (10 mg/kg) - a human anti-PD-L1 antibody. Assessments included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Results: As of December 31, 2016, 51 patients were treated and followed for a median of 24.2 months (range, 16.1-31.5). Most patients had cutaneous (n = 28 [54.9{\%}]) or ocular (n = 16 [31.4{\%}]) melanoma and had received a median of 2 prior lines of therapy (range, 0-4), including ipilimumab (n = 26 [51.0{\%}]). The confirmed ORR was 21.6{\%} (95{\%} CI, 11.3-35.3; complete response, 7.8{\%}; partial response, 13.7{\%}). The median duration of response was not estimable (95{\%} CI, 2.6 months-not estimable). Median PFS and OS were 3.1 months (95{\%} CI, 1.4-6.3) and 17.2 months (95{\%} CI, 6.6-not estimable), respectively. Subgroup analyses suggested meaningful clinical activity (ORR [95{\%} CI]) in patients with non-ocular melanoma (31.4{\%} [16.9-49.3]), PD-L1-positive tumors (42.1{\%} [20.3-66.5]), or prior ipilimumab therapy (30.8{\%} [14.3-51.8]). Thirty-nine patients (76.5{\%}) had a treatment-related adverse event (TRAE), most commonly infusion-related reaction (29.4{\%}), fatigue (17.6{\%}), and chills (11.8{\%}); 4 patients (7.8{\%}) had a grade 3 TRAE. Five patients (9.8{\%}) had an immune-related TRAE (all were grade 1/2). No grade 4 TRAEs or treatment-related deaths were reported. Conclusion: Avelumab showed durable responses, promising survival outcomes, and an acceptable safety profile in patients with previously treated metastatic melanoma. Trial registration: ClinicalTrials.gov identifier: NCT01772004.",
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    author = "Ulrich Keilholz and Mehnert, {Janice M.} and Sebastian Bauer and Hugues Bourgeois and Patel, {Manish R.} and Donald Gravenor and Nemunaitis, {John J.} and Matthew Taylor and Lucjan Wyrwicz and Lee, {Keun Wook} and Vijay Kasturi and Kevin Chin and {Von Heydebreck}, Anja and Gulley, {James L.}",
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    TY - JOUR

    T1 - Avelumab in patients with previously treated metastatic melanoma

    T2 - Phase 1b results from the JAVELIN Solid Tumor trial

    AU - Keilholz, Ulrich

    AU - Mehnert, Janice M.

    AU - Bauer, Sebastian

    AU - Bourgeois, Hugues

    AU - Patel, Manish R.

    AU - Gravenor, Donald

    AU - Nemunaitis, John J.

    AU - Taylor, Matthew

    AU - Wyrwicz, Lucjan

    AU - Lee, Keun Wook

    AU - Kasturi, Vijay

    AU - Chin, Kevin

    AU - Von Heydebreck, Anja

    AU - Gulley, James L.

    PY - 2019/1/16

    Y1 - 2019/1/16

    N2 - Background: We report phase 1b data from patients enrolled in the JAVELIN Solid Tumor clinical trial (NCT01772004) with unresectable stage IIIC or IV melanoma that had progressed after ≥1 line of therapy for metastatic disease. Patients and methods: Patients received avelumab (10 mg/kg) - a human anti-PD-L1 antibody. Assessments included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Results: As of December 31, 2016, 51 patients were treated and followed for a median of 24.2 months (range, 16.1-31.5). Most patients had cutaneous (n = 28 [54.9%]) or ocular (n = 16 [31.4%]) melanoma and had received a median of 2 prior lines of therapy (range, 0-4), including ipilimumab (n = 26 [51.0%]). The confirmed ORR was 21.6% (95% CI, 11.3-35.3; complete response, 7.8%; partial response, 13.7%). The median duration of response was not estimable (95% CI, 2.6 months-not estimable). Median PFS and OS were 3.1 months (95% CI, 1.4-6.3) and 17.2 months (95% CI, 6.6-not estimable), respectively. Subgroup analyses suggested meaningful clinical activity (ORR [95% CI]) in patients with non-ocular melanoma (31.4% [16.9-49.3]), PD-L1-positive tumors (42.1% [20.3-66.5]), or prior ipilimumab therapy (30.8% [14.3-51.8]). Thirty-nine patients (76.5%) had a treatment-related adverse event (TRAE), most commonly infusion-related reaction (29.4%), fatigue (17.6%), and chills (11.8%); 4 patients (7.8%) had a grade 3 TRAE. Five patients (9.8%) had an immune-related TRAE (all were grade 1/2). No grade 4 TRAEs or treatment-related deaths were reported. Conclusion: Avelumab showed durable responses, promising survival outcomes, and an acceptable safety profile in patients with previously treated metastatic melanoma. Trial registration: ClinicalTrials.gov identifier: NCT01772004.

    AB - Background: We report phase 1b data from patients enrolled in the JAVELIN Solid Tumor clinical trial (NCT01772004) with unresectable stage IIIC or IV melanoma that had progressed after ≥1 line of therapy for metastatic disease. Patients and methods: Patients received avelumab (10 mg/kg) - a human anti-PD-L1 antibody. Assessments included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Results: As of December 31, 2016, 51 patients were treated and followed for a median of 24.2 months (range, 16.1-31.5). Most patients had cutaneous (n = 28 [54.9%]) or ocular (n = 16 [31.4%]) melanoma and had received a median of 2 prior lines of therapy (range, 0-4), including ipilimumab (n = 26 [51.0%]). The confirmed ORR was 21.6% (95% CI, 11.3-35.3; complete response, 7.8%; partial response, 13.7%). The median duration of response was not estimable (95% CI, 2.6 months-not estimable). Median PFS and OS were 3.1 months (95% CI, 1.4-6.3) and 17.2 months (95% CI, 6.6-not estimable), respectively. Subgroup analyses suggested meaningful clinical activity (ORR [95% CI]) in patients with non-ocular melanoma (31.4% [16.9-49.3]), PD-L1-positive tumors (42.1% [20.3-66.5]), or prior ipilimumab therapy (30.8% [14.3-51.8]). Thirty-nine patients (76.5%) had a treatment-related adverse event (TRAE), most commonly infusion-related reaction (29.4%), fatigue (17.6%), and chills (11.8%); 4 patients (7.8%) had a grade 3 TRAE. Five patients (9.8%) had an immune-related TRAE (all were grade 1/2). No grade 4 TRAEs or treatment-related deaths were reported. Conclusion: Avelumab showed durable responses, promising survival outcomes, and an acceptable safety profile in patients with previously treated metastatic melanoma. Trial registration: ClinicalTrials.gov identifier: NCT01772004.

    KW - Avelumab

    KW - Cutaneous melanoma

    KW - Immune checkpoint inhibitor

    KW - Ocular melanoma

    KW - PD-L1

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