Efficacy and Safety of Avelumab Treatment in Patients with Advanced Unresectable Mesothelioma: Phase 1b Results from the JAVELIN Solid Tumor Trial

Raffit Hassan, Anish Thomas, John J. Nemunaitis, Manish R. Patel, Jaafar Bennouna, Franklin L. Chen, Jean Pierre Delord, Afshin Dowlati, Samith T. Kochuparambil, Matthew Taylor, John D. Powderly, Ulka N. Vaishampayan, Claire Verschraegen, Hans Juergen Grote, Anja Von Heydebreck, Kevin Chin, James L. Gulley

    Research output: Contribution to journalArticle

    5 Citations (Scopus)

    Abstract

    Importance: Patients with malignant mesothelioma whose disease has progressed after platinum and pemetrexed treatment have limited options. Anti-programmed cell death 1 (PD-1) antibodies have antitumor activity in this disease, but little is known about the activity of anti-programmed cell death ligand 1 (PD-L1) antibodies in patients with mesothelioma. Objective: To assess the efficacy and safety of avelumab in a cohort of patients with previously treated mesothelioma. Design, Setting, and Participants: Phase 1b open-label study (JAVELIN Solid Tumor) in patients with unresectable mesothelioma that progressed after platinum and pemetrexed treatment, enrolled at 25 sites in 3 countries between September 9, 2014, and July 22, 2015. Interventions: Participants 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 included confirmed best overall response based on Response Evaluation Criteria In Solid Tumors, version 1.1; duration of response; progression-free survival (PFS); overall survival (OS); PD-L1 expression-based analyses; and safety. Results: Of 53 patients treated with avelumab, the median age was 67 (range, 32-84) years; 32 (60%) were male. As of December 31, 2016, median follow-up was 24.8 (range, 16.8-27.8) months. Twenty patients (38%) had 3 or more previous lines of therapy (median, 2; range, 1-8). The confirmed objective response rate (ORR) was 9% (5 patients; 95% CI, 3.1%-20.7%), with complete response in 1 patient and partial response in 4 patients. Responses were durable (median, 15.2 months; 95% CI, 11.1 to not estimable months) and occurred in patients with PD-L1-positive tumors (3 of 16; ORR, 19%; 95% CI, 4.0%-45.6%) and PD-L1-negative tumors (2 of 27; ORR, 7%; 95% CI, 0.9%-24.3%) based on a 5% or greater PD-L1 cutoff. Disease control rate was 58% (31 patients). Median PFS was 4.1 (95% CI, 1.4-6.2) months, and the 12-month PFS rate was 17.4% (95% CI, 7.7%-30.4%). Median OS was 10.7 (95% CI, 6.4-20.2) months, and the median 12-month OS rate was 43.8% (95% CI, 29.8%-57.0%). Five patients (9%) had a grade 3 or 4 treatment-related adverse event, and 3 (6%) had a grade 3 or 4 immune-related, treatment-related adverse event. There were no treatment-related deaths. Conclusions and Relevance: Avelumab showed durable antitumor activity and disease control with an acceptable safety profile in a heavily pretreated cohort of patients with mesothelioma. Trial Registration: ClinicalTrials.gov identifier: NCT01772004.

    Original languageEnglish (US)
    JournalJAMA oncology
    DOIs
    StateAccepted/In press - Jan 1 2018

    Fingerprint

    Mesothelioma
    Safety
    Neoplasms
    Cell Death
    Pemetrexed
    Therapeutics
    Ligands
    Disease-Free Survival
    Platinum
    avelumab
    Survival Rate
    Survival
    Antibodies
    Poisons
    Cerebral Palsy
    Disease Progression
    Outcome Assessment (Health Care)

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

    Cite this

    Efficacy and Safety of Avelumab Treatment in Patients with Advanced Unresectable Mesothelioma : Phase 1b Results from the JAVELIN Solid Tumor Trial. / Hassan, Raffit; Thomas, Anish; Nemunaitis, John J.; Patel, Manish R.; Bennouna, Jaafar; Chen, Franklin L.; Delord, Jean Pierre; Dowlati, Afshin; Kochuparambil, Samith T.; Taylor, Matthew; Powderly, John D.; Vaishampayan, Ulka N.; Verschraegen, Claire; Grote, Hans Juergen; Von Heydebreck, Anja; Chin, Kevin; Gulley, James L.

    In: JAMA oncology, 01.01.2018.

    Research output: Contribution to journalArticle

    Hassan, R, Thomas, A, Nemunaitis, JJ, Patel, MR, Bennouna, J, Chen, FL, Delord, JP, Dowlati, A, Kochuparambil, ST, Taylor, M, Powderly, JD, Vaishampayan, UN, Verschraegen, C, Grote, HJ, Von Heydebreck, A, Chin, K & Gulley, JL 2018, 'Efficacy and Safety of Avelumab Treatment in Patients with Advanced Unresectable Mesothelioma: Phase 1b Results from the JAVELIN Solid Tumor Trial', JAMA oncology. https://doi.org/10.1001/jamaoncol.2018.5428
    Hassan, Raffit ; Thomas, Anish ; Nemunaitis, John J. ; Patel, Manish R. ; Bennouna, Jaafar ; Chen, Franklin L. ; Delord, Jean Pierre ; Dowlati, Afshin ; Kochuparambil, Samith T. ; Taylor, Matthew ; Powderly, John D. ; Vaishampayan, Ulka N. ; Verschraegen, Claire ; Grote, Hans Juergen ; Von Heydebreck, Anja ; Chin, Kevin ; Gulley, James L. / Efficacy and Safety of Avelumab Treatment in Patients with Advanced Unresectable Mesothelioma : Phase 1b Results from the JAVELIN Solid Tumor Trial. In: JAMA oncology. 2018.
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    title = "Efficacy and Safety of Avelumab Treatment in Patients with Advanced Unresectable Mesothelioma: Phase 1b Results from the JAVELIN Solid Tumor Trial",
    abstract = "Importance: Patients with malignant mesothelioma whose disease has progressed after platinum and pemetrexed treatment have limited options. Anti-programmed cell death 1 (PD-1) antibodies have antitumor activity in this disease, but little is known about the activity of anti-programmed cell death ligand 1 (PD-L1) antibodies in patients with mesothelioma. Objective: To assess the efficacy and safety of avelumab in a cohort of patients with previously treated mesothelioma. Design, Setting, and Participants: Phase 1b open-label study (JAVELIN Solid Tumor) in patients with unresectable mesothelioma that progressed after platinum and pemetrexed treatment, enrolled at 25 sites in 3 countries between September 9, 2014, and July 22, 2015. Interventions: Participants 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 included confirmed best overall response based on Response Evaluation Criteria In Solid Tumors, version 1.1; duration of response; progression-free survival (PFS); overall survival (OS); PD-L1 expression-based analyses; and safety. Results: Of 53 patients treated with avelumab, the median age was 67 (range, 32-84) years; 32 (60{\%}) were male. As of December 31, 2016, median follow-up was 24.8 (range, 16.8-27.8) months. Twenty patients (38{\%}) had 3 or more previous lines of therapy (median, 2; range, 1-8). The confirmed objective response rate (ORR) was 9{\%} (5 patients; 95{\%} CI, 3.1{\%}-20.7{\%}), with complete response in 1 patient and partial response in 4 patients. Responses were durable (median, 15.2 months; 95{\%} CI, 11.1 to not estimable months) and occurred in patients with PD-L1-positive tumors (3 of 16; ORR, 19{\%}; 95{\%} CI, 4.0{\%}-45.6{\%}) and PD-L1-negative tumors (2 of 27; ORR, 7{\%}; 95{\%} CI, 0.9{\%}-24.3{\%}) based on a 5{\%} or greater PD-L1 cutoff. Disease control rate was 58{\%} (31 patients). Median PFS was 4.1 (95{\%} CI, 1.4-6.2) months, and the 12-month PFS rate was 17.4{\%} (95{\%} CI, 7.7{\%}-30.4{\%}). Median OS was 10.7 (95{\%} CI, 6.4-20.2) months, and the median 12-month OS rate was 43.8{\%} (95{\%} CI, 29.8{\%}-57.0{\%}). Five patients (9{\%}) had a grade 3 or 4 treatment-related adverse event, and 3 (6{\%}) had a grade 3 or 4 immune-related, treatment-related adverse event. There were no treatment-related deaths. Conclusions and Relevance: Avelumab showed durable antitumor activity and disease control with an acceptable safety profile in a heavily pretreated cohort of patients with mesothelioma. Trial Registration: ClinicalTrials.gov identifier: NCT01772004.",
    author = "Raffit Hassan and Anish Thomas and Nemunaitis, {John J.} and Patel, {Manish R.} and Jaafar Bennouna and Chen, {Franklin L.} and Delord, {Jean Pierre} and Afshin Dowlati and Kochuparambil, {Samith T.} and Matthew Taylor and Powderly, {John D.} and Vaishampayan, {Ulka N.} and Claire Verschraegen and Grote, {Hans Juergen} and {Von Heydebreck}, Anja and Kevin Chin and Gulley, {James L.}",
    year = "2018",
    month = "1",
    day = "1",
    doi = "10.1001/jamaoncol.2018.5428",
    language = "English (US)",
    journal = "JAMA oncology",
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    publisher = "American Medical Association",

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    TY - JOUR

    T1 - Efficacy and Safety of Avelumab Treatment in Patients with Advanced Unresectable Mesothelioma

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

    AU - Hassan, Raffit

    AU - Thomas, Anish

    AU - Nemunaitis, John J.

    AU - Patel, Manish R.

    AU - Bennouna, Jaafar

    AU - Chen, Franklin L.

    AU - Delord, Jean Pierre

    AU - Dowlati, Afshin

    AU - Kochuparambil, Samith T.

    AU - Taylor, Matthew

    AU - Powderly, John D.

    AU - Vaishampayan, Ulka N.

    AU - Verschraegen, Claire

    AU - Grote, Hans Juergen

    AU - Von Heydebreck, Anja

    AU - Chin, Kevin

    AU - Gulley, James L.

    PY - 2018/1/1

    Y1 - 2018/1/1

    N2 - Importance: Patients with malignant mesothelioma whose disease has progressed after platinum and pemetrexed treatment have limited options. Anti-programmed cell death 1 (PD-1) antibodies have antitumor activity in this disease, but little is known about the activity of anti-programmed cell death ligand 1 (PD-L1) antibodies in patients with mesothelioma. Objective: To assess the efficacy and safety of avelumab in a cohort of patients with previously treated mesothelioma. Design, Setting, and Participants: Phase 1b open-label study (JAVELIN Solid Tumor) in patients with unresectable mesothelioma that progressed after platinum and pemetrexed treatment, enrolled at 25 sites in 3 countries between September 9, 2014, and July 22, 2015. Interventions: Participants 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 included confirmed best overall response based on Response Evaluation Criteria In Solid Tumors, version 1.1; duration of response; progression-free survival (PFS); overall survival (OS); PD-L1 expression-based analyses; and safety. Results: Of 53 patients treated with avelumab, the median age was 67 (range, 32-84) years; 32 (60%) were male. As of December 31, 2016, median follow-up was 24.8 (range, 16.8-27.8) months. Twenty patients (38%) had 3 or more previous lines of therapy (median, 2; range, 1-8). The confirmed objective response rate (ORR) was 9% (5 patients; 95% CI, 3.1%-20.7%), with complete response in 1 patient and partial response in 4 patients. Responses were durable (median, 15.2 months; 95% CI, 11.1 to not estimable months) and occurred in patients with PD-L1-positive tumors (3 of 16; ORR, 19%; 95% CI, 4.0%-45.6%) and PD-L1-negative tumors (2 of 27; ORR, 7%; 95% CI, 0.9%-24.3%) based on a 5% or greater PD-L1 cutoff. Disease control rate was 58% (31 patients). Median PFS was 4.1 (95% CI, 1.4-6.2) months, and the 12-month PFS rate was 17.4% (95% CI, 7.7%-30.4%). Median OS was 10.7 (95% CI, 6.4-20.2) months, and the median 12-month OS rate was 43.8% (95% CI, 29.8%-57.0%). Five patients (9%) had a grade 3 or 4 treatment-related adverse event, and 3 (6%) had a grade 3 or 4 immune-related, treatment-related adverse event. There were no treatment-related deaths. Conclusions and Relevance: Avelumab showed durable antitumor activity and disease control with an acceptable safety profile in a heavily pretreated cohort of patients with mesothelioma. Trial Registration: ClinicalTrials.gov identifier: NCT01772004.

    AB - Importance: Patients with malignant mesothelioma whose disease has progressed after platinum and pemetrexed treatment have limited options. Anti-programmed cell death 1 (PD-1) antibodies have antitumor activity in this disease, but little is known about the activity of anti-programmed cell death ligand 1 (PD-L1) antibodies in patients with mesothelioma. Objective: To assess the efficacy and safety of avelumab in a cohort of patients with previously treated mesothelioma. Design, Setting, and Participants: Phase 1b open-label study (JAVELIN Solid Tumor) in patients with unresectable mesothelioma that progressed after platinum and pemetrexed treatment, enrolled at 25 sites in 3 countries between September 9, 2014, and July 22, 2015. Interventions: Participants 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 included confirmed best overall response based on Response Evaluation Criteria In Solid Tumors, version 1.1; duration of response; progression-free survival (PFS); overall survival (OS); PD-L1 expression-based analyses; and safety. Results: Of 53 patients treated with avelumab, the median age was 67 (range, 32-84) years; 32 (60%) were male. As of December 31, 2016, median follow-up was 24.8 (range, 16.8-27.8) months. Twenty patients (38%) had 3 or more previous lines of therapy (median, 2; range, 1-8). The confirmed objective response rate (ORR) was 9% (5 patients; 95% CI, 3.1%-20.7%), with complete response in 1 patient and partial response in 4 patients. Responses were durable (median, 15.2 months; 95% CI, 11.1 to not estimable months) and occurred in patients with PD-L1-positive tumors (3 of 16; ORR, 19%; 95% CI, 4.0%-45.6%) and PD-L1-negative tumors (2 of 27; ORR, 7%; 95% CI, 0.9%-24.3%) based on a 5% or greater PD-L1 cutoff. Disease control rate was 58% (31 patients). Median PFS was 4.1 (95% CI, 1.4-6.2) months, and the 12-month PFS rate was 17.4% (95% CI, 7.7%-30.4%). Median OS was 10.7 (95% CI, 6.4-20.2) months, and the median 12-month OS rate was 43.8% (95% CI, 29.8%-57.0%). Five patients (9%) had a grade 3 or 4 treatment-related adverse event, and 3 (6%) had a grade 3 or 4 immune-related, treatment-related adverse event. There were no treatment-related deaths. Conclusions and Relevance: Avelumab showed durable antitumor activity and disease control with an acceptable safety profile in a heavily pretreated cohort of patients with mesothelioma. Trial Registration: ClinicalTrials.gov identifier: NCT01772004.

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