Design and Rationale for a Phase III, Randomized, Placebo-controlled Trial of Durvalumab With or Without Tremelimumab After Concurrent Chemoradiotherapy for Patients With Limited-stage Small-cell Lung Cancer: The ADRIATIC Study

Suresh Senan; Isamu Okamoto; Gyeong won Lee; Yuanbin Chen; Seiji Niho; Gabriel Mak; Wenliang Yao; Norah Shire; Haiyi Jiang; Byoung Chul Cho

doi:10.1016/j.cllc.2019.12.006

Design and Rationale for a Phase III, Randomized, Placebo-controlled Trial of Durvalumab With or Without Tremelimumab After Concurrent Chemoradiotherapy for Patients With Limited-stage Small-cell Lung Cancer: The ADRIATIC Study

Suresh Senan, Isamu Okamoto, Gyeong won Lee, Yuanbin Chen, Seiji Niho, Gabriel Mak, Wenliang Yao, Norah Shire, Haiyi Jiang, Byoung Chul Cho

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

33 Citations (Scopus)

Abstract

Limited-stage (LS) small-cell lung cancer (SCLC) remains an area of high unmet medical need. The standard-of-care therapy comprises curative-intent platinum-based chemotherapy with concurrent radiotherapy (cCRT), which can be followed by prophylactic brain irradiation and then observation. However, most patients will relapse. Durvalumab (antiprogrammed cell death ligand-1) has enhanced the efficacy outcomes after cCRT for patients with unresectable, stage III non-small-cell lung cancer. Recently, durvalumab combined with platinum-etoposide demonstrated a significant survival benefit compared with platinum-etoposide as first-line treatment of patients with extensive-stage SCLC and has also shown antitumor activity as monotherapy and combined with tremelimumab (anticytotoxic T-lymphocyte–associated antigen-4) in pretreated patients with extensive-stage SCLC. ADRIATIC, a phase III, randomized, double-blind, placebo-controlled, multicenter, global study (ClinicalTrials.gov identifier, NCT03703297), is designed to investigate the efficacy of durvalumab, with or without tremelimumab, as consolidation therapy for patients with LS-SCLC without disease progression after cCRT. Approximately 600 patients with documented histologic or cytologic LS-SCLC, World Health Organization/Eastern Cooperative Oncology Group performance status 0 or 1, and no progression after 4 cycles of cCRT will be randomized (1:1:1) to treatment (durvalumab 1500 mg plus placebo every 4 weeks [q4w] for 4 cycles, followed by durvalumab 1500 mg q4w; durvalumab 1500 mg plus tremelimumab 75 mg q4w for 4 cycles, followed by durvalumab 1500 mg q4w; or dual placebo q4w for 4 cycles, followed by single placebo q4w) within 1 to 42 days of completing cCRT, stratified by stage and receipt of prophylactic brain irradiation. The primary endpoints are progression-free survival and overall survival. The secondary endpoints are overall survival and progression-free survival rates, objective response rate, and safety and tolerability. Recruitment began in September 2018.

Original language	English
Pages (from-to)	e84-e88
Journal	Clinical Lung Cancer
Volume	21
Issue number	2
DOIs	https://doi.org/10.1016/j.cllc.2019.12.006
Publication status	Published - 2020 Mar

Bibliographical note

Funding Information:
Medical writing support, which was in accordance with Good Publication Practice guidelines, was provided by Craig Turner, MSc, of Cirrus Communications, an Ashfield company (Macclesfield, UK), and was funded by AstraZeneca .

Funding Information:
S.S. has received research grants and personal fees (advisory boards and speaker fees) from AstraZeneca and personal fees (advisory boards) from Merck and Celgene, all outside the submitted work. I.O. has received research grants from Boehringer-Ingelheim during the conduct of the study; research grants and personal fees from AstraZeneca, Taiho Pharmaceutical, Chugai Pharma, Boehringer-Ingelheim, Ono Pharmaceutical, MSD Oncology, Lilly, and Bristol-Myers Squibb; research grants from Astellas Pharma, Novartis, and AbbVie; and personal fees from Pfizer, all outside the submitted work. Y.C. has received research grants from AstraZeneca, ISPEN, Roche, and Bristol-Myers Squibb; personal fees (consultancy, speakers’ bureau) from AstraZeneca, Genentech, Bristol-Myers Squibb, Novartis, and Takeda; personal fees (speakers’ bureau) from Merck, Eli Lilly, and Guardant Health; and personal fees (consultancy) from Pfizer and Array Biopharma, all outside the submitted work. S.N. has received research grants from Merck Serono; research grants and personal fees (honoraria) from AstraZeneca, Pfizer, MSD, and Eli Lilly; and personal fees (honoraria) from Chugai, Taiho, Bristol-Myers Squibb, Novartis, Boehringer-Ingelheim, Shionogi, and Yakult, all outside the submitted work. B.C.C. has received research funding from Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, and MSD; has provided consultancy for Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, and MSD; has stock ownership in TheraCanVac Inc, Gencurix Inc, and Bridgebio Therapeutics; and has received royalties from Champions Oncology. G.M. and N.S. are full-time employees of AstraZeneca. W.Y. and H.J. are full-time employees of AstraZeneca and have stock ownership in AstraZeneca. The remaining author declares that they have no competing interests.Medical writing support, which was in accordance with Good Publication Practice guidelines, was provided by Craig Turner, MSc, of Cirrus Communications, an Ashfield company (Macclesfield, UK), and was funded by AstraZeneca.

Publisher Copyright:
© 2020

All Science Journal Classification (ASJC) codes

Oncology
Pulmonary and Respiratory Medicine
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Dive into the research topics of 'Design and Rationale for a Phase III, Randomized, Placebo-controlled Trial of Durvalumab With or Without Tremelimumab After Concurrent Chemoradiotherapy for Patients With Limited-stage Small-cell Lung Cancer: The ADRIATIC Study'. Together they form a unique fingerprint.

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Senan, S., Okamoto, I., Lee, G. W., Chen, Y., Niho, S., Mak, G., Yao, W., Shire, N., Jiang, H., & Cho, B. C. (2020). Design and Rationale for a Phase III, Randomized, Placebo-controlled Trial of Durvalumab With or Without Tremelimumab After Concurrent Chemoradiotherapy for Patients With Limited-stage Small-cell Lung Cancer: The ADRIATIC Study. Clinical Lung Cancer, 21(2), e84-e88. https://doi.org/10.1016/j.cllc.2019.12.006

@article{cefb598b0f5c405aa3fc3614dd910584,

title = "Design and Rationale for a Phase III, Randomized, Placebo-controlled Trial of Durvalumab With or Without Tremelimumab After Concurrent Chemoradiotherapy for Patients With Limited-stage Small-cell Lung Cancer: The ADRIATIC Study",

abstract = "Limited-stage (LS) small-cell lung cancer (SCLC) remains an area of high unmet medical need. The standard-of-care therapy comprises curative-intent platinum-based chemotherapy with concurrent radiotherapy (cCRT), which can be followed by prophylactic brain irradiation and then observation. However, most patients will relapse. Durvalumab (antiprogrammed cell death ligand-1) has enhanced the efficacy outcomes after cCRT for patients with unresectable, stage III non-small-cell lung cancer. Recently, durvalumab combined with platinum-etoposide demonstrated a significant survival benefit compared with platinum-etoposide as first-line treatment of patients with extensive-stage SCLC and has also shown antitumor activity as monotherapy and combined with tremelimumab (anticytotoxic T-lymphocyte–associated antigen-4) in pretreated patients with extensive-stage SCLC. ADRIATIC, a phase III, randomized, double-blind, placebo-controlled, multicenter, global study (ClinicalTrials.gov identifier, NCT03703297), is designed to investigate the efficacy of durvalumab, with or without tremelimumab, as consolidation therapy for patients with LS-SCLC without disease progression after cCRT. Approximately 600 patients with documented histologic or cytologic LS-SCLC, World Health Organization/Eastern Cooperative Oncology Group performance status 0 or 1, and no progression after 4 cycles of cCRT will be randomized (1:1:1) to treatment (durvalumab 1500 mg plus placebo every 4 weeks [q4w] for 4 cycles, followed by durvalumab 1500 mg q4w; durvalumab 1500 mg plus tremelimumab 75 mg q4w for 4 cycles, followed by durvalumab 1500 mg q4w; or dual placebo q4w for 4 cycles, followed by single placebo q4w) within 1 to 42 days of completing cCRT, stratified by stage and receipt of prophylactic brain irradiation. The primary endpoints are progression-free survival and overall survival. The secondary endpoints are overall survival and progression-free survival rates, objective response rate, and safety and tolerability. Recruitment began in September 2018.",

author = "Suresh Senan and Isamu Okamoto and Lee, {Gyeong won} and Yuanbin Chen and Seiji Niho and Gabriel Mak and Wenliang Yao and Norah Shire and Haiyi Jiang and Cho, {Byoung Chul}",

note = "Funding Information: Medical writing support, which was in accordance with Good Publication Practice guidelines, was provided by Craig Turner, MSc, of Cirrus Communications, an Ashfield company (Macclesfield, UK), and was funded by AstraZeneca . Funding Information: S.S. has received research grants and personal fees (advisory boards and speaker fees) from AstraZeneca and personal fees (advisory boards) from Merck and Celgene, all outside the submitted work. I.O. has received research grants from Boehringer-Ingelheim during the conduct of the study; research grants and personal fees from AstraZeneca, Taiho Pharmaceutical, Chugai Pharma, Boehringer-Ingelheim, Ono Pharmaceutical, MSD Oncology, Lilly, and Bristol-Myers Squibb; research grants from Astellas Pharma, Novartis, and AbbVie; and personal fees from Pfizer, all outside the submitted work. Y.C. has received research grants from AstraZeneca, ISPEN, Roche, and Bristol-Myers Squibb; personal fees (consultancy, speakers{\textquoteright} bureau) from AstraZeneca, Genentech, Bristol-Myers Squibb, Novartis, and Takeda; personal fees (speakers{\textquoteright} bureau) from Merck, Eli Lilly, and Guardant Health; and personal fees (consultancy) from Pfizer and Array Biopharma, all outside the submitted work. S.N. has received research grants from Merck Serono; research grants and personal fees (honoraria) from AstraZeneca, Pfizer, MSD, and Eli Lilly; and personal fees (honoraria) from Chugai, Taiho, Bristol-Myers Squibb, Novartis, Boehringer-Ingelheim, Shionogi, and Yakult, all outside the submitted work. B.C.C. has received research funding from Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, and MSD; has provided consultancy for Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, and MSD; has stock ownership in TheraCanVac Inc, Gencurix Inc, and Bridgebio Therapeutics; and has received royalties from Champions Oncology. G.M. and N.S. are full-time employees of AstraZeneca. W.Y. and H.J. are full-time employees of AstraZeneca and have stock ownership in AstraZeneca. The remaining author declares that they have no competing interests.Medical writing support, which was in accordance with Good Publication Practice guidelines, was provided by Craig Turner, MSc, of Cirrus Communications, an Ashfield company (Macclesfield, UK), and was funded by AstraZeneca. Publisher Copyright: {\textcopyright} 2020",

year = "2020",

month = mar,

doi = "10.1016/j.cllc.2019.12.006",

language = "English",

volume = "21",

pages = "e84--e88",

journal = "Clinical Lung Cancer",

issn = "1525-7304",

publisher = "Elsevier",

number = "2",

}

Senan, S, Okamoto, I, Lee, GW, Chen, Y, Niho, S, Mak, G, Yao, W, Shire, N, Jiang, H & Cho, BC 2020, 'Design and Rationale for a Phase III, Randomized, Placebo-controlled Trial of Durvalumab With or Without Tremelimumab After Concurrent Chemoradiotherapy for Patients With Limited-stage Small-cell Lung Cancer: The ADRIATIC Study', Clinical Lung Cancer, vol. 21, no. 2, pp. e84-e88. https://doi.org/10.1016/j.cllc.2019.12.006

Design and Rationale for a Phase III, Randomized, Placebo-controlled Trial of Durvalumab With or Without Tremelimumab After Concurrent Chemoradiotherapy for Patients With Limited-stage Small-cell Lung Cancer: The ADRIATIC Study. / Senan, Suresh; Okamoto, Isamu; Lee, Gyeong won et al.
In: Clinical Lung Cancer, Vol. 21, No. 2, 03.2020, p. e84-e88.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Design and Rationale for a Phase III, Randomized, Placebo-controlled Trial of Durvalumab With or Without Tremelimumab After Concurrent Chemoradiotherapy for Patients With Limited-stage Small-cell Lung Cancer

T2 - The ADRIATIC Study

AU - Senan, Suresh

AU - Okamoto, Isamu

AU - Lee, Gyeong won

AU - Chen, Yuanbin

AU - Niho, Seiji

AU - Mak, Gabriel

AU - Yao, Wenliang

AU - Shire, Norah

AU - Jiang, Haiyi

AU - Cho, Byoung Chul

N1 - Funding Information: Medical writing support, which was in accordance with Good Publication Practice guidelines, was provided by Craig Turner, MSc, of Cirrus Communications, an Ashfield company (Macclesfield, UK), and was funded by AstraZeneca . Funding Information: S.S. has received research grants and personal fees (advisory boards and speaker fees) from AstraZeneca and personal fees (advisory boards) from Merck and Celgene, all outside the submitted work. I.O. has received research grants from Boehringer-Ingelheim during the conduct of the study; research grants and personal fees from AstraZeneca, Taiho Pharmaceutical, Chugai Pharma, Boehringer-Ingelheim, Ono Pharmaceutical, MSD Oncology, Lilly, and Bristol-Myers Squibb; research grants from Astellas Pharma, Novartis, and AbbVie; and personal fees from Pfizer, all outside the submitted work. Y.C. has received research grants from AstraZeneca, ISPEN, Roche, and Bristol-Myers Squibb; personal fees (consultancy, speakers’ bureau) from AstraZeneca, Genentech, Bristol-Myers Squibb, Novartis, and Takeda; personal fees (speakers’ bureau) from Merck, Eli Lilly, and Guardant Health; and personal fees (consultancy) from Pfizer and Array Biopharma, all outside the submitted work. S.N. has received research grants from Merck Serono; research grants and personal fees (honoraria) from AstraZeneca, Pfizer, MSD, and Eli Lilly; and personal fees (honoraria) from Chugai, Taiho, Bristol-Myers Squibb, Novartis, Boehringer-Ingelheim, Shionogi, and Yakult, all outside the submitted work. B.C.C. has received research funding from Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, and MSD; has provided consultancy for Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, and MSD; has stock ownership in TheraCanVac Inc, Gencurix Inc, and Bridgebio Therapeutics; and has received royalties from Champions Oncology. G.M. and N.S. are full-time employees of AstraZeneca. W.Y. and H.J. are full-time employees of AstraZeneca and have stock ownership in AstraZeneca. The remaining author declares that they have no competing interests.Medical writing support, which was in accordance with Good Publication Practice guidelines, was provided by Craig Turner, MSc, of Cirrus Communications, an Ashfield company (Macclesfield, UK), and was funded by AstraZeneca. Publisher Copyright: © 2020

PY - 2020/3

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N2 - Limited-stage (LS) small-cell lung cancer (SCLC) remains an area of high unmet medical need. The standard-of-care therapy comprises curative-intent platinum-based chemotherapy with concurrent radiotherapy (cCRT), which can be followed by prophylactic brain irradiation and then observation. However, most patients will relapse. Durvalumab (antiprogrammed cell death ligand-1) has enhanced the efficacy outcomes after cCRT for patients with unresectable, stage III non-small-cell lung cancer. Recently, durvalumab combined with platinum-etoposide demonstrated a significant survival benefit compared with platinum-etoposide as first-line treatment of patients with extensive-stage SCLC and has also shown antitumor activity as monotherapy and combined with tremelimumab (anticytotoxic T-lymphocyte–associated antigen-4) in pretreated patients with extensive-stage SCLC. ADRIATIC, a phase III, randomized, double-blind, placebo-controlled, multicenter, global study (ClinicalTrials.gov identifier, NCT03703297), is designed to investigate the efficacy of durvalumab, with or without tremelimumab, as consolidation therapy for patients with LS-SCLC without disease progression after cCRT. Approximately 600 patients with documented histologic or cytologic LS-SCLC, World Health Organization/Eastern Cooperative Oncology Group performance status 0 or 1, and no progression after 4 cycles of cCRT will be randomized (1:1:1) to treatment (durvalumab 1500 mg plus placebo every 4 weeks [q4w] for 4 cycles, followed by durvalumab 1500 mg q4w; durvalumab 1500 mg plus tremelimumab 75 mg q4w for 4 cycles, followed by durvalumab 1500 mg q4w; or dual placebo q4w for 4 cycles, followed by single placebo q4w) within 1 to 42 days of completing cCRT, stratified by stage and receipt of prophylactic brain irradiation. The primary endpoints are progression-free survival and overall survival. The secondary endpoints are overall survival and progression-free survival rates, objective response rate, and safety and tolerability. Recruitment began in September 2018.

AB - Limited-stage (LS) small-cell lung cancer (SCLC) remains an area of high unmet medical need. The standard-of-care therapy comprises curative-intent platinum-based chemotherapy with concurrent radiotherapy (cCRT), which can be followed by prophylactic brain irradiation and then observation. However, most patients will relapse. Durvalumab (antiprogrammed cell death ligand-1) has enhanced the efficacy outcomes after cCRT for patients with unresectable, stage III non-small-cell lung cancer. Recently, durvalumab combined with platinum-etoposide demonstrated a significant survival benefit compared with platinum-etoposide as first-line treatment of patients with extensive-stage SCLC and has also shown antitumor activity as monotherapy and combined with tremelimumab (anticytotoxic T-lymphocyte–associated antigen-4) in pretreated patients with extensive-stage SCLC. ADRIATIC, a phase III, randomized, double-blind, placebo-controlled, multicenter, global study (ClinicalTrials.gov identifier, NCT03703297), is designed to investigate the efficacy of durvalumab, with or without tremelimumab, as consolidation therapy for patients with LS-SCLC without disease progression after cCRT. Approximately 600 patients with documented histologic or cytologic LS-SCLC, World Health Organization/Eastern Cooperative Oncology Group performance status 0 or 1, and no progression after 4 cycles of cCRT will be randomized (1:1:1) to treatment (durvalumab 1500 mg plus placebo every 4 weeks [q4w] for 4 cycles, followed by durvalumab 1500 mg q4w; durvalumab 1500 mg plus tremelimumab 75 mg q4w for 4 cycles, followed by durvalumab 1500 mg q4w; or dual placebo q4w for 4 cycles, followed by single placebo q4w) within 1 to 42 days of completing cCRT, stratified by stage and receipt of prophylactic brain irradiation. The primary endpoints are progression-free survival and overall survival. The secondary endpoints are overall survival and progression-free survival rates, objective response rate, and safety and tolerability. Recruitment began in September 2018.

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Design and Rationale for a Phase III, Randomized, Placebo-controlled Trial of Durvalumab With or Without Tremelimumab After Concurrent Chemoradiotherapy for Patients With Limited-stage Small-cell Lung Cancer: The ADRIATIC Study

Abstract

Bibliographical note

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UN SDGs

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