Avelumab in patients with previously treated metastatic melanoma

Phase 1b results from the JAVELIN Solid Tumor trial

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

Research output: Contribution to journalArticle

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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

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

All Science Journal Classification (ASJC) codes

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

Cite this

Keilholz, Ulrich ; Mehnert, Janice ; Bauer, Sebastian ; Bourgeois, Hugues ; Patel, Manish R. ; Gravenor, Donald ; Nemunaitis, John J. ; Taylor, Matthew H. ; 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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title = "Avelumab in patients with previously treated metastatic melanoma: Phase 1b results from the JAVELIN Solid Tumor trial",
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.",
author = "Ulrich Keilholz and Janice Mehnert and Sebastian Bauer and Hugues Bourgeois and Patel, {Manish R.} and Donald Gravenor and Nemunaitis, {John J.} and Taylor, {Matthew H.} and Lucjan Wyrwicz and Lee, {Keun Wook} and Vijay Kasturi and Kevin Chin and {Von Heydebreck}, Anja and Gulley, {James L.}",
year = "2019",
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Keilholz, U, Mehnert, J, Bauer, S, Bourgeois, H, Patel, MR, Gravenor, D, Nemunaitis, JJ, Taylor, MH, 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

Avelumab in patients with previously treated metastatic melanoma : Phase 1b results from the JAVELIN Solid Tumor trial. / Keilholz, Ulrich; Mehnert, Janice; Bauer, Sebastian; Bourgeois, Hugues; Patel, Manish R.; Gravenor, Donald; Nemunaitis, John J.; Taylor, Matthew H.; 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

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

AU - Bauer, Sebastian

AU - Bourgeois, Hugues

AU - Patel, Manish R.

AU - Gravenor, Donald

AU - Nemunaitis, John J.

AU - Taylor, Matthew H.

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.

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