Efficacy and Safety of Avelumab for Patients with Recurrent or Refractory Ovarian Cancer: Phase 1b Results from the JAVELIN Solid Tumor Trial

Mary L. Disis, Matthew H. Taylor, Karen Kelly, J. Thaddeus Beck, Michael Gordon, Kathleen M. Moore, Manish R. Patel, Jorge Chaves, Haeseong Park, Alain C. Mita, Erika P. Hamilton, Christina M. Annunziata, Hans Juergen Grote, Anja Von Heydebreck, Jaspreet Grewal, Vikram Chand, James L. Gulley

Research output: Contribution to journalArticle

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Abstract

Importance: Current treatment options for progressive ovarian cancer provide limited benefit, particularly in patients whose disease has become resistant to platinum-based chemotherapy. Objective: To assess the efficacy and safety of avelumab, an anti-programmed death-ligand 1 agent, in a cohort of patients with previously treated recurrent or refractory ovarian cancer. Design, Setting, and Participants: In an expansion cohort of a phase 1b, open-label study (JAVELIN Solid Tumor), 125 patients with advanced ovarian cancer who had received chemotherapy including a platinum agent were enrolled between November 6, 2013, and August 27, 2015. Statistical analysis was performed from December 31, 2016, to October 9, 2018. Intervention: Patients received avelumab, 10 mg/kg, every 2 weeks until disease progression, unacceptable toxic effects, or withdrawal from the study. Main Outcomes and Measures: Prespecified end points in this cohort included confirmed best overall response (per Response Evaluation Criteria In Solid Tumors, version 1.1), immune-related best overall response, duration of response, progression-free survival, overall survival, results of programmed death-ligand 1 expression-based analyses, and safety. Results: A total of 125 women (median age, 62.0 years [range, 27-84 years]) who had received a median of 3 prior lines of treatment (range, 0-10) for advanced disease were enrolled in the study. Patients received avelumab for a median of 2.8 months (range, 0.5-27.4 months), with a median follow-up of 26.6 months (range, 16-38 months). A confirmed objective response occurred in 12 patients (9.6%; 95% CI, 5.1%-16.2%), including a complete response in 1 patient (0.8%) and a partial response in 11 patients (8.8%). The 1-year progression-free survival rate was 10.2% (95% CI, 5.4%-16.7%) and median overall survival was 11.2 months (95% CI, 8.7-15.4 months). Infusion-related reactions occurred in 25 patients (20.0%). Other frequent treatment-related adverse events (any grade event occurring in ≥10% of patients) were fatigue (17 [13.6%]), diarrhea (15 [12.0%]), and nausea (14 [11.2%]). Grade 3 or higher treatment-related adverse events occurred in 9 patients (7.2%), of which only the level of lipase increased (3 [2.4%]) occurred in more than 1 patient. Twenty-one patients (16.8%) had an immune-related adverse event of any grade. No treatment-related deaths occurred. Conclusions and Relevance: Avelumab demonstrated antitumor activity and acceptable safety in heavily pretreated patients with recurrent or refractory ovarian cancer.

Original languageEnglish (US)
JournalJAMA oncology
DOIs
StateAccepted/In press - Jan 1 2019

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Patient Safety
Ovarian Neoplasms
Neoplasms
avelumab
Platinum
Safety
Disease-Free Survival
Ligands
Therapeutics
Drug Therapy
Survival
Poisons
Lipase
Nausea
Fatigue
Disease Progression
Diarrhea
Survival Rate

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Efficacy and Safety of Avelumab for Patients with Recurrent or Refractory Ovarian Cancer : Phase 1b Results from the JAVELIN Solid Tumor Trial. / Disis, Mary L.; Taylor, Matthew H.; Kelly, Karen; Beck, J. Thaddeus; Gordon, Michael; Moore, Kathleen M.; Patel, Manish R.; Chaves, Jorge; Park, Haeseong; Mita, Alain C.; Hamilton, Erika P.; Annunziata, Christina M.; Grote, Hans Juergen; Von Heydebreck, Anja; Grewal, Jaspreet; Chand, Vikram; Gulley, James L.

In: JAMA oncology, 01.01.2019.

Research output: Contribution to journalArticle

Disis, ML, Taylor, MH, Kelly, K, Beck, JT, Gordon, M, Moore, KM, Patel, MR, Chaves, J, Park, H, Mita, AC, Hamilton, EP, Annunziata, CM, Grote, HJ, Von Heydebreck, A, Grewal, J, Chand, V & Gulley, JL 2019, 'Efficacy and Safety of Avelumab for Patients with Recurrent or Refractory Ovarian Cancer: Phase 1b Results from the JAVELIN Solid Tumor Trial', JAMA oncology. https://doi.org/10.1001/jamaoncol.2018.6258
Disis, Mary L. ; Taylor, Matthew H. ; Kelly, Karen ; Beck, J. Thaddeus ; Gordon, Michael ; Moore, Kathleen M. ; Patel, Manish R. ; Chaves, Jorge ; Park, Haeseong ; Mita, Alain C. ; Hamilton, Erika P. ; Annunziata, Christina M. ; Grote, Hans Juergen ; Von Heydebreck, Anja ; Grewal, Jaspreet ; Chand, Vikram ; Gulley, James L. / Efficacy and Safety of Avelumab for Patients with Recurrent or Refractory Ovarian Cancer : Phase 1b Results from the JAVELIN Solid Tumor Trial. In: JAMA oncology. 2019.
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title = "Efficacy and Safety of Avelumab for Patients with Recurrent or Refractory Ovarian Cancer: Phase 1b Results from the JAVELIN Solid Tumor Trial",
abstract = "Importance: Current treatment options for progressive ovarian cancer provide limited benefit, particularly in patients whose disease has become resistant to platinum-based chemotherapy. Objective: To assess the efficacy and safety of avelumab, an anti-programmed death-ligand 1 agent, in a cohort of patients with previously treated recurrent or refractory ovarian cancer. Design, Setting, and Participants: In an expansion cohort of a phase 1b, open-label study (JAVELIN Solid Tumor), 125 patients with advanced ovarian cancer who had received chemotherapy including a platinum agent were enrolled between November 6, 2013, and August 27, 2015. Statistical analysis was performed from December 31, 2016, to October 9, 2018. Intervention: Patients received avelumab, 10 mg/kg, every 2 weeks until disease progression, unacceptable toxic effects, or withdrawal from the study. Main Outcomes and Measures: Prespecified end points in this cohort included confirmed best overall response (per Response Evaluation Criteria In Solid Tumors, version 1.1), immune-related best overall response, duration of response, progression-free survival, overall survival, results of programmed death-ligand 1 expression-based analyses, and safety. Results: A total of 125 women (median age, 62.0 years [range, 27-84 years]) who had received a median of 3 prior lines of treatment (range, 0-10) for advanced disease were enrolled in the study. Patients received avelumab for a median of 2.8 months (range, 0.5-27.4 months), with a median follow-up of 26.6 months (range, 16-38 months). A confirmed objective response occurred in 12 patients (9.6{\%}; 95{\%} CI, 5.1{\%}-16.2{\%}), including a complete response in 1 patient (0.8{\%}) and a partial response in 11 patients (8.8{\%}). The 1-year progression-free survival rate was 10.2{\%} (95{\%} CI, 5.4{\%}-16.7{\%}) and median overall survival was 11.2 months (95{\%} CI, 8.7-15.4 months). Infusion-related reactions occurred in 25 patients (20.0{\%}). Other frequent treatment-related adverse events (any grade event occurring in ≥10{\%} of patients) were fatigue (17 [13.6{\%}]), diarrhea (15 [12.0{\%}]), and nausea (14 [11.2{\%}]). Grade 3 or higher treatment-related adverse events occurred in 9 patients (7.2{\%}), of which only the level of lipase increased (3 [2.4{\%}]) occurred in more than 1 patient. Twenty-one patients (16.8{\%}) had an immune-related adverse event of any grade. No treatment-related deaths occurred. Conclusions and Relevance: Avelumab demonstrated antitumor activity and acceptable safety in heavily pretreated patients with recurrent or refractory ovarian cancer.",
author = "Disis, {Mary L.} and Taylor, {Matthew H.} and Karen Kelly and Beck, {J. Thaddeus} and Michael Gordon and Moore, {Kathleen M.} and Patel, {Manish R.} and Jorge Chaves and Haeseong Park and Mita, {Alain C.} and Hamilton, {Erika P.} and Annunziata, {Christina M.} and Grote, {Hans Juergen} and {Von Heydebreck}, Anja and Jaspreet Grewal and Vikram Chand and Gulley, {James L.}",
year = "2019",
month = "1",
day = "1",
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TY - JOUR

T1 - Efficacy and Safety of Avelumab for Patients with Recurrent or Refractory Ovarian Cancer

T2 - Phase 1b Results from the JAVELIN Solid Tumor Trial

AU - Disis, Mary L.

AU - Taylor, Matthew H.

AU - Kelly, Karen

AU - Beck, J. Thaddeus

AU - Gordon, Michael

AU - Moore, Kathleen M.

AU - Patel, Manish R.

AU - Chaves, Jorge

AU - Park, Haeseong

AU - Mita, Alain C.

AU - Hamilton, Erika P.

AU - Annunziata, Christina M.

AU - Grote, Hans Juergen

AU - Von Heydebreck, Anja

AU - Grewal, Jaspreet

AU - Chand, Vikram

AU - Gulley, James L.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Importance: Current treatment options for progressive ovarian cancer provide limited benefit, particularly in patients whose disease has become resistant to platinum-based chemotherapy. Objective: To assess the efficacy and safety of avelumab, an anti-programmed death-ligand 1 agent, in a cohort of patients with previously treated recurrent or refractory ovarian cancer. Design, Setting, and Participants: In an expansion cohort of a phase 1b, open-label study (JAVELIN Solid Tumor), 125 patients with advanced ovarian cancer who had received chemotherapy including a platinum agent were enrolled between November 6, 2013, and August 27, 2015. Statistical analysis was performed from December 31, 2016, to October 9, 2018. Intervention: Patients received avelumab, 10 mg/kg, every 2 weeks until disease progression, unacceptable toxic effects, or withdrawal from the study. Main Outcomes and Measures: Prespecified end points in this cohort included confirmed best overall response (per Response Evaluation Criteria In Solid Tumors, version 1.1), immune-related best overall response, duration of response, progression-free survival, overall survival, results of programmed death-ligand 1 expression-based analyses, and safety. Results: A total of 125 women (median age, 62.0 years [range, 27-84 years]) who had received a median of 3 prior lines of treatment (range, 0-10) for advanced disease were enrolled in the study. Patients received avelumab for a median of 2.8 months (range, 0.5-27.4 months), with a median follow-up of 26.6 months (range, 16-38 months). A confirmed objective response occurred in 12 patients (9.6%; 95% CI, 5.1%-16.2%), including a complete response in 1 patient (0.8%) and a partial response in 11 patients (8.8%). The 1-year progression-free survival rate was 10.2% (95% CI, 5.4%-16.7%) and median overall survival was 11.2 months (95% CI, 8.7-15.4 months). Infusion-related reactions occurred in 25 patients (20.0%). Other frequent treatment-related adverse events (any grade event occurring in ≥10% of patients) were fatigue (17 [13.6%]), diarrhea (15 [12.0%]), and nausea (14 [11.2%]). Grade 3 or higher treatment-related adverse events occurred in 9 patients (7.2%), of which only the level of lipase increased (3 [2.4%]) occurred in more than 1 patient. Twenty-one patients (16.8%) had an immune-related adverse event of any grade. No treatment-related deaths occurred. Conclusions and Relevance: Avelumab demonstrated antitumor activity and acceptable safety in heavily pretreated patients with recurrent or refractory ovarian cancer.

AB - Importance: Current treatment options for progressive ovarian cancer provide limited benefit, particularly in patients whose disease has become resistant to platinum-based chemotherapy. Objective: To assess the efficacy and safety of avelumab, an anti-programmed death-ligand 1 agent, in a cohort of patients with previously treated recurrent or refractory ovarian cancer. Design, Setting, and Participants: In an expansion cohort of a phase 1b, open-label study (JAVELIN Solid Tumor), 125 patients with advanced ovarian cancer who had received chemotherapy including a platinum agent were enrolled between November 6, 2013, and August 27, 2015. Statistical analysis was performed from December 31, 2016, to October 9, 2018. Intervention: Patients received avelumab, 10 mg/kg, every 2 weeks until disease progression, unacceptable toxic effects, or withdrawal from the study. Main Outcomes and Measures: Prespecified end points in this cohort included confirmed best overall response (per Response Evaluation Criteria In Solid Tumors, version 1.1), immune-related best overall response, duration of response, progression-free survival, overall survival, results of programmed death-ligand 1 expression-based analyses, and safety. Results: A total of 125 women (median age, 62.0 years [range, 27-84 years]) who had received a median of 3 prior lines of treatment (range, 0-10) for advanced disease were enrolled in the study. Patients received avelumab for a median of 2.8 months (range, 0.5-27.4 months), with a median follow-up of 26.6 months (range, 16-38 months). A confirmed objective response occurred in 12 patients (9.6%; 95% CI, 5.1%-16.2%), including a complete response in 1 patient (0.8%) and a partial response in 11 patients (8.8%). The 1-year progression-free survival rate was 10.2% (95% CI, 5.4%-16.7%) and median overall survival was 11.2 months (95% CI, 8.7-15.4 months). Infusion-related reactions occurred in 25 patients (20.0%). Other frequent treatment-related adverse events (any grade event occurring in ≥10% of patients) were fatigue (17 [13.6%]), diarrhea (15 [12.0%]), and nausea (14 [11.2%]). Grade 3 or higher treatment-related adverse events occurred in 9 patients (7.2%), of which only the level of lipase increased (3 [2.4%]) occurred in more than 1 patient. Twenty-one patients (16.8%) had an immune-related adverse event of any grade. No treatment-related deaths occurred. Conclusions and Relevance: Avelumab demonstrated antitumor activity and acceptable safety in heavily pretreated patients with recurrent or refractory ovarian cancer.

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