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 H.
AU - Wyrwicz, Lucjan
AU - Lee, Keun Wook
AU - Kasturi, Vijay
AU - Chin, Kevin
AU - Von Heydebreck, Anja
AU - Gulley, James L.
N1 - Publisher Copyright:
© 2019 The Author(s).
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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UR - http://www.scopus.com/inward/citedby.url?scp=85060148678&partnerID=8YFLogxK
U2 - 10.1186/s40425-018-0459-y
DO - 10.1186/s40425-018-0459-y
M3 - Article
C2 - 30651126
AN - SCOPUS:85060148678
SN - 2051-1426
VL - 7
JO - Journal for immunotherapy of cancer
JF - Journal for immunotherapy of cancer
IS - 1
M1 - 12
ER -