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Clinical Trial
. 2025 Mar;26(3):331-342.
doi: 10.1016/S1470-2045(25)00001-4.

Activity and safety of atezolizumab plus carboplatin and paclitaxel in patients with advanced or recurrent thymic carcinoma (MARBLE): a multicentre, single-arm, phase 2 trial

Takehito Shukuya  1 , Tetsuhiko Asao  2 , Yasushi Goto  3 , Tomoyasu Mimori  2 , Koichi Takayama  4 , Kyoichi Kaira  5 , Hiroshi Tanaka  6 , Ryo Ko  7 , Yoshihiro Amano  8 , Motoko Tachihara  9 , Takuji Suzuki  10 , Junko Tanizaki  11 , Shunichi Sugawara  12 , Yoshitaka Zenke  13 , Yukina Shirai  2 , Takuo Hayashi  14 , Keita Mori  15 , Kazuhisa Takahashi  2
Affiliations
Clinical Trial

Activity and safety of atezolizumab plus carboplatin and paclitaxel in patients with advanced or recurrent thymic carcinoma (MARBLE): a multicentre, single-arm, phase 2 trial

Takehito Shukuya et al. Lancet Oncol. 2025 Mar.

Abstract

Background: Despite the poor prognosis of advanced or recurrent thymic carcinoma, the rarity of thymic carcinoma has delayed the development and introduction of novel pharmacotherapy options. Carboplatin plus paclitaxel remains a standard treatment for chemotherapy-naive advanced or recurrent thymic carcinoma. We evaluated the activity and safety of atezolizumab combined with chemotherapy.

Methods: In this multicentre, single-arm, phase 2 trial in 15 hospitals in Japan, patients with metastatic or recurrent thymic carcinoma were treated with atezolizumab plus carboplatin and paclitaxel. Eligible patients were aged 20 years or older with histologically confirmed Masaoka stage III, IVA, or IVB thymic carcinoma not amenable for definitive treatment or recurrent thymic carcinoma after definitive treatment; and no previous history of systemic drug therapy for thymic carcinoma. The data of sex and race were defined via self-report. Patients received atezolizumab 1200 mg, carboplatin area under the curve 6 mg/mL per min, and paclitaxel 200 mg/m2 intravenously every 3 weeks for up to six cycles, followed by atezolizumab 1200 mg intravenously every 3 weeks for up to 2 years until progression or unacceptable toxicity. The primary endpoint was objective response rate, based on an independent central review. The primary endpoint and safety were assessed in the per-protocol set. This trial was registered at Japan Registry of Clinical Trials, jRCT2031220144, and is closed to enrolment.

Findings: Between June 14, 2022, and July 6, 2023, 48 patients were enrolled and included in the efficacy and safety analyses. Median follow-up was 15·3 months (IQR 13·8-16·6). 29 (60%) patients were male and 19 (40%) of 48 patients were female. Median age of patients was 67·5 years (IQR 56·5-72·5). All patients were Asian. The objective response rate was 56% (95% CI 41-71; Fisher's exact test p<0·0001); 27 (56%) of 48 participants had a partial response. The most common adverse reactions of grade 3 or worse were neutropenia (27 [56%] of 48 patients), leukopenia (16 [33%]), febrile neutropenia (11 [23%]), and maculopapular rash (six [13%]). There were no treatment-related deaths and eight deaths overall.

Interpretation: In previously untreated advanced thymic carcinoma, the addition of atezolizumab to carboplatin and paclitaxel conferred clinically meaningful antitumour activity with a manageable safety profile. Thus, atezolizumab plus carboplatin and paclitaxel might become a viable treatment option for previously untreated advanced or recurrent thymic carcinoma.

Funding: Chugai Pharmaceutical.

Translations: For the Japanese translation of the abstract see Supplementary Materials section.

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Conflict of interest statement

Declaration of interests TSh reports grant support for this study from Chugai Pharmaceutical; grant support from AstraZeneca, Boehringer Ingelheim, Chugai Pharmaceutical, MSD, and Novartis; and honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, MSD, Nippon Kayaku, Novartis, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, and Takeda. TA reports honoraria from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Merck Biopharma, MSD, Nippon Kayaku, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, and Takeda Pharmaceutical. YG reports grant support from AIQVIA Services Japan, MSD, Astellas Pharma, AstraZeneca, AbbVie, Amgen, Syneos Health Clinical, Sysmex Corporation, CMIC, Novartis Pharma, Bayer Pharmaceuticals, Bristol-Myers Squibb, MedPace Japan, Janssen Pharma, Clinical Research Support Center Kyushu, SATOMI, Ono Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, Chugai Pharmaceutical, NPO Thoracic Oncology Research Group, Eli Lilly Japan, Peferred Network, Kyorin, MSD, and Guardant Health; honoraria from Eli Lilly, Chugai Pharmaceutical, Taiho, Boehringer Ingelheim, Ono, Bristol Myers Squibb, Pfizer, MSD, Novartis, Merck, and Thermo Fisher; participation on an advisory board for AstraZeneca, Chugai Pharmaceutical, Boehringer Ingelheim, Eli Lilly, Glaxo Smith Kline, Taiho Pharmaceutical, Pfizer, Novartis, Kyorin, Guardant Health., Illumina, Daiichi Sankyo, Merck, MSD, Ono Pharmaceutical, Janssen; and a leadership or fiduciary role at Cancer Net Japan, and JAMT. TM reports grant support from AstraZeneca, Chugai Pharmaceutical, Eli Lilly Japan; honoraria from Eli Lilly Japan, Ono Pharmaceutical, Bristol-Myers Squibb, Chugai Pharmaceutical, AstraZeneca, MSD, Novartis pharmaceuticals, Takeda Pharmaceutical, Taiho Pharmaceutical, Nippon Boehringer Ingelheim, Daiichi Sankyo, and Pfizer Japan. KoT reports grant support for Taiho Pharmaceutical, and Chugai-Roche; honoraria from AstraZeneca, MSD, Ono Pharmaceutical, Daiichi Sankyo, Chugai-Roche, Boehringer-Ingelheim, and Eli-Lilly. KK reports grant support from AstraZeneca; honoraria from Chugai Pharmaceutical, AstraZeneca, Bristol Myers Squibb, Ono Pharmaceutical, MSD, Boehringer Ingelheim, Taiho, and Eli Lilly. HT reports institutional grant support from Astra Zeneca, Chugai Pharmaceutical, MSD, Ono Pharmaceutical, Bristol Myers Squibb, Daiichi-Sankyo pharmaceutical, Eli Lilly, Takeda pharmaceutical, Taiho pharmaceutical, Merck, Boehringer Ingelheim, Amgen, and AbbVie; honoraria from Astra Zeneca, Chugai Pharmaceutical, MSD, Ono Pharmaceutical, Bristol Myers Squibb, Daiichi-Sankyo pharmaceutical, Eli Lilly, Takeda pharmaceutical, Taiho pharmaceutical, Merck, Boehringer Ingelheim, Sun pharmaceutical, Eisai, Novartis, Pfizer, and Celltrion. RK reports grant support from AstraZeneca and MSD; honoraria from Taiho Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, AstraZeneca, Ono Pharmaceutical, Daiichi Sankyo, MSD, Bristol-Myers Squibb, and Takeda Pharmaceutical. MT reports grant support from AstraZeneca, Chugai Pharmaceutical, and Eli Lilly; and honoraria from Eli Lilly, Ono Pharmaceutical, Bristol-Myers Squibb, Chugai Pharmaceutical, AstraZeneca, MSD, Novartis pharmaceuticals, Takeda Pharmaceutical, Taiho Pharmaceutical, Nippon Boehringer Ingelheim, Daiichi Sankyo, and Pfizer. JT reports honoraria from Boehringer-Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Janssen Pharmaceutical, MSD, Nihon Medi-Physics, Nippon Kayaku, Taiho Pharmaceutical, Ono pharmaceutical, Pfizer, AstraZeneca, and Takeda Pharmaceuticals; and participation on an advisory board for AstraZeneca, and AbbVie. SS reports grant support from AnHeart, AstraZeneca, Chugai Pharma, MSD, Daiichi Sankyo, Bristol-Myers Squibb, Nippon Boehringer Ingelheim, Ono Pharmaceutical, AbbVie, Amgen, Taiho Pharmaceutical, Accerise, A2 Healthcare, Parexel, EPS, PPD, and Syneos; and honoraria from AstraZeneca, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, MSD, Nippon Boehringer Ingelheim, Pfizer, Taiho Pharmaceutical, Eli Lilly, Novartis, Kyowa Kirin, Takeda Pharmaceutical, Nippon Kayaku, Merck, Amgen, AbbVie, Otsuka Pharmaceutical, Thermo Fisher Scientific, Towa Pharmaceutical, Sysmex, and Eisai. YZ reports grant support from Amgen, AstraZeneca, Daiichi Sankyo, Merck Biopharma, MSD, GSK, and Chugai Pharmaceutical; and honoraria from AstraZenca, Eli Lilly, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol-Meyers Squibb, Takeda Pharmaceutical, Boheringer-Ingelheim, Taiho Pharmaceutical, MSD, Novartis, Pfizer, Nippon Kayaku, Kyowa Kirin, Amgen, and Guradant health. TH reports honoraria from AstraZeneca, Chugai Pharmaceutical, Taiho Pharmaceutical, Amgen, AbbVie, Boehringer Ingelheim, Novartis, and Thermo Fisher Scientific. KM reports honoraria from Chugai Pharmaceutical, Eli Lilly, and Ono Pharmaceutical. KaT reports grant support from Chugai Pharmaceutical, Nippon Boehringer Ingelheim, Nippon Shinyaku, Tsumura, Pfizer, Taiho Pharmaceutical, Kyorin, Teijin Pharma, Sanofi, Ono Pharmaceutical, Novartis Pharma, Shionogi, Eli Lilly Japan, Bayer Yakuhin, Daiichi Sankyo, Nipro Pharma, Asahi Kasei Pharma, Nippon Kayaku, Takeda Pharmaceutical, and Kyowa Kirin; honoraria from Chugai Pharmaceutical, Nippon Boehringer Ingelheim, MSD, Pfizer, AstraZeneca, Taiho Pharmaceutical, Kyorin Pharmaceutical, Merck Biopharma, Ono Pharmaceutical, Nippon Kayaku, Novartis Pharma, Eli Lilly Japan, Sumitomo Dainippon Pharma, Bristol-Myers, Meiji Seika Pharma, Takeda Pharmaceutical, Viatris, Janssen Pharmaceutical, Abbott Japan, Thermo Fisher Scientific; and leadership or fiduciary role in The Japan Lung Cancer Society and The Japan Respiratory Society. All other authors declare no competing interests.

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