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Avelumab monotherapy as first-line or second-line treatment in patients with metastatic renal cell carcinoma: phase Ib results from the JAVELIN Solid Tumor trial.

ABSTRACT: BACKGROUND:Antibodies targeting programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) have shown clinical activity in the treatment of metastatic renal cell carcinoma (mRCC). This phase Ib cohort of the JAVELIN Solid Tumor trial assessed the efficacy and safety of avelumab (anti-PD-L1) monotherapy in patients with mRCC as either first-line (1?L) or second-line (2?L) treatment. METHODS:Patients with mRCC with a clear-cell component who were treatment naive (1?L subgroup) or had disease progression after one prior line of therapy (2?L subgroup) received avelumab 10?mg/kg intravenous infusion every 2?weeks. Endpoints included confirmed best overall response, duration of response (DOR), progression-free survival (PFS), overall survival (OS), PD-L1 expression, and safety. RESULTS:A total of 62 patients were enrolled in the 1?L subgroup, and 20 patients were enrolled in the 2?L subgroup. In the 1?L and 2?L subgroups, confirmed objective response rates were 16.1 and 10.0%, median DOR was 9.9?months (95% confidence interval [CI], 2.8-not evaluable) and not evaluable (95% CI, 6.9-not evaluable), median PFS was 8.3?months (95% CI, 5.5-9.5) and 5.6?months (95% CI, 2.3-9.6), and median OS was not evaluable (95% CI, not evaluable) and 16.9?months (95% CI, 8.3-not evaluable), respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 51 patients in the 1?L subgroup (82.3%) and 14 patients in the 2?L subgroup (70.0%). Grade???3 TRAEs occurred in eight patients in the 1?L subgroup (12.9%) and one patient in the 2?L subgroup (5.0%). No treatment-related deaths occurred. CONCLUSION:Avelumab showed clinical activity and a manageable safety profile in both the 1?L and 2?L treatment setting in patients with mRCC. These data support the use of avelumab in combination with other agents in mRCC. TRIAL REGISTRATION:ClinicalTrials.gov: NCT01772004 ; registered 21 January, 2013.

SUBMITTER: Vaishampayan U

PROVIDER: S-EPMC6813090 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Avelumab monotherapy as first-line or second-line treatment in patients with metastatic renal cell carcinoma: phase Ib results from the JAVELIN Solid Tumor trial.

Vaishampayan Ulka U Schöffski Patrick P Ravaud Alain A Borel Christian C Peguero Julio J Chaves Jorge J Morris John C JC Kotecki Nuria N Smakal Martin M Zhou Dongli D Guenther Silke S Bajars Marcis M Gulley James L JL

Journal for immunotherapy of cancer 20191024 1

<h4>Background</h4>Antibodies targeting programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) have shown clinical activity in the treatment of metastatic renal cell carcinoma (mRCC). This phase Ib cohort of the JAVELIN Solid Tumor trial assessed the efficacy and safety of avelumab (anti-PD-L1) monotherapy in patients with mRCC as either first-line (1 L) or second-line (2 L) treatment.<h4>Methods</h4>Patients with mRCC with a clear-cell component who were treatment naive (1 L subgroup) o ...[more]

PMID: 31651359

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Project description:BACKGROUND:Anti-programmed cell death ligand 1 (PD-L1)/programmed cell death 1 antibodies have shown clinical activity in platinum-treated metastatic urothelial carcinoma, resulting in regulatory approval of several agents, including avelumab (anti-PD-L1). We report ?2-year follow-up data for avelumab treatment and exploratory subgroup analyses in patients with urothelial carcinoma. METHODS:Patients with previously treated advanced/metastatic urothelial carcinoma, pooled from two cohorts of the phase Ib JAVELIN Solid Tumor trial, received avelumab 10?mg/kg every 2 weeks until disease progression, unacceptable toxicity or withdrawal. End points included best overall response and progression-free survival (PFS) per RECIST V.1.1, overall survival (OS) and safety. Post hoc analyses included objective response rates (ORRs) in subgroups defined by established high-risk/poor-prognosis characteristics and association between time to response and outcome. RESULTS:249 patients received avelumab; efficacy was assessed in 242 postplatinum patients. Median follow-up was 31.9 months (range 24-43), and median treatment duration was 2.8 months (range 0.5-42.8). The confirmed ORR was 16.5% (95% CI 12.1% to 21.8%; complete response in 4.1% and partial response in 12.4%). Median duration of response was 20.5 months (95%?CI 9.7 months to not estimable). Median PFS was 1.6 months (95%?CI 1.4 to 2.7 months) and the 12-month PFS rate was 16.8% (95% CI 11.9% to 22.4%). Median OS was 7.0 months (95%?CI 5.9 to 8.5 months) and the 24-month OS rate was 20.1% (95% CI 15.2% to 25.4%). In post hoc exploratory analyses, avelumab showed antitumor activity in high-risk subgroups, including elderly patients and those with renal insufficiency or upper tract disease; ORRs were numerically lower in patients with liver metastases or low albumin levels. Objective response achieved by 3 months versus later was associated with longer OS (median not reached (95%?CI 18.9 months to not estimable) vs 7.1 months (95%?CI 5.2 to 9.0 months)). Safety findings were consistent with previously reported 6-month analyses. CONCLUSIONS:After ?2 years of follow-up, avelumab showed prolonged efficacy and acceptable safety in patients with platinum-treated advanced/metastatic urothelial carcinoma, including high-risk subgroups. Survival appeared longer in patients who responded within 3 months. Long-term safety findings were consistent with earlier reports with avelumab treatment in this patient population.

Project description:BACKGROUND:We evaluated the antitumor activity and safety of avelumab, a human anti-PD-L1 IgG1 antibody, as first-line switch-maintenance (1?L-mn) or second-line (2?L) treatment in patients with advanced gastric/gastroesophageal cancer (GC/GEJC) previously treated with chemotherapy. METHODS:In a phase 1b expansion cohort, patients without (1?L-mn) or with (2?L) disease progression following first-line chemotherapy for advanced GC/GEJC received avelumab 10?mg/kg intravenously every 2?weeks. Endpoints included best overall response, progression-free survival (PFS), overall survival (OS), and safety. RESULTS:Overall, 150 patients were enrolled (1?L-mn, n?=?90; 2?L, n?=?60) and median follow-up in the 1?L-mn and 2?L subgroups was 36.0 and 33.7?months, respectively. The confirmed objective response rate was 6.7% in both subgroups (95% CI, 2.5-13.9% and 1.8-16.2%, respectively), including complete responses in 2.2% of the 1?L-mn subgroup (n?=?2). In the 1?L-mn and 2?L subgroups, median duration of response was 21.4?months (95% CI, 4.0-not estimable) and 3.5?months (95% CI, 2.8-8.3) and disease control rates were 56.7 and 28.3%, respectively. Median PFS in the 1?L-mn and 2?L subgroups was 2.8?months (95% CI, 2.3-4.1) and 1.4?months (95% CI, 1.3-1.5), with 6-month PFS rates of 23.0% (95% CI, 14.7-32.4%) and 7.9% (95% CI, 2.6-17.2%), and median OS was 11.1?months (95% CI, 8.9-13.7) and 6.6?months (95% CI, 5.4-9.4), respectively. In the 1?L-mn subgroup, median OS measured from start of 1?L chemotherapy was 18.7?months (95% CI, 15.4-20.6). Across both subgroups, 20.7% had an infusion-related reaction of any grade. Other common treatment-related adverse events (TRAEs) of any grade included fatigue (10.0%) and nausea (6.7%). Treatment-related serious adverse events occurred in 4.0% of patients. Overall, 8.7% had a grade??3 TRAE, including 1 treatment-related death. CONCLUSION:Avelumab showed clinical activity and an acceptable safety profile in patients with GC/GEJC. TRIAL REGISTRATION:ClinicalTrials.gov NCT01772004 ; registered 21 January 2013.

Project description:BackgroundRecurrent and/or metastatic (R/M) disease develops in approximately 65% of patients with squamous cell carcinoma of the head and neck (SCCHN) and is associated with a poor prognosis. Immune checkpoint inhibitors have proven effective in multiple tumor types, including R/M SCCHN. We report the efficacy and safety of avelumab (antiprogrammed death ligand 1 antibody) in an expansion cohort of patients with platinum-refractory/ineligible R/M SCCHN enrolled in the phase I JAVELIN Solid Tumor trial (NCT01772004).MethodsEligible patients with R/M SCCHN were aged ≥18 years and had received ≥1 line of platinum-based chemotherapy with disease progression or recurrence within 6 months of the last dose or were ineligible for platinum-based chemotherapy. All patients received avelumab 10 mg/kg every 2 weeks. Tumor assessments were carried out by a blinded independent review committee (IRC) and investigators according to Response Evaluation Criteria in Solid Tumors V.1.1 (RECIST 1.1). Key endpoints included best overall response, duration of response (DOR) and progression-free survival (PFS) assessed by IRC and investigator per RECIST 1.1, overall survival (OS), and safety.ResultsBetween April 24, 2015, and November 13, 2015, 153 patients were enrolled. Patients had a median of two prior lines of therapy for metastatic or locally advanced disease (range 0-6); 12 patients (7.8%) were not eligible for platinum-based chemotherapy. At data cut-off (December 31, 2017), the confirmed objective response rate was 9.2% (95% CI 5.1% to 14.9%) assessed by IRC and 13.1% (95% CI 8.2% to 19.5%) assessed by investigator. Median DOR was not reached (95% CI 4.2 to not estimable) based on IRC assessment. Median PFS was 1.4 months (95% CI 1.4 to 2.6) assessed by IRC and 1.8 months (95% CI 1.4 to 2.7) assessed by investigator; median OS was 8.0 months (95% CI 6.5 to 10.2). Any-grade treatment-related adverse events (TRAEs) occurred in 83 patients (54.2%) and were grade ≥3 in 10 patients (6.5%). The most common TRAEs were fatigue (n=19, 12.4%), fever (n=14, 9.2%), pruritus (n=12, 7.8%), and chills (n=11, 7.2%), and there were no treatment-related deaths.ConclusionAvelumab showed clinical activity and was associated with a low rate of grade ≥3 TRAEs in heavily pretreated patients with platinum-refractory/ineligible R/M SCCHN.

Dataset Information

Avelumab monotherapy as first-line or second-line treatment in patients with metastatic renal cell carcinoma: phase Ib results from the JAVELIN Solid Tumor trial.

Publications

Avelumab monotherapy as first-line or second-line treatment in patients with metastatic renal cell carcinoma: phase Ib results from the JAVELIN Solid Tumor trial.

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