LBA8 - Phase II trial of atezolizumab plus carboplatin and paclitaxel in patients with metastatic or recurrent thymic carcinoma: Marble study

Background

Despite the limited prognosis of advanced or recurrent thymic carcinoma (TC), the development and introduction of novel drugs is often delayed due to its rarity. Carboplatin plus paclitaxel remains the standard of care for chemotherapy-naive advanced or recurrent TC. In this study, we evaluated the efficacy and safety of atezolizumab in combination with chemotherapy.

Methods

In this multicenter, single-arm, open-label phase II study, chemotherapy-naive patients with metastatic or recurrent TC were treated with atezolizumab (1200 mg/body, day1) plus carboplatin (AUC 6, day1) and paclitaxel (200 mg/m², day1) every 3 weeks for up to 6 cycles, followed by atezolizumab (1200 mg/body, day1) every 3 weeks for up to 2 years until progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR), based on an independent central review. The secondary endpoints were the investigator-assessed ORR, disease control rate, progression-free survival (PFS), overall survival (OS), and safety. Assuming ORR threshold of 30%, and expected ORR of 52%, sample size of 47 patients were calculated based on the exact binomial distribution with a two-sided α of 0.05 and β of 0.2.

Results

Between May 2022 and July 2023, 48 patients were enrolled and all patients were included in the efficacy and safety analysis. The median follow-up time was 15.3 months. The ORR was 56.3% (95%CI [confidence interval], 41.2 - 70.5%, p < 0.0001). 27 (56.3%) of 48 patients had a partial response and 20 (41.7%) had stable disease. Median PFS was 9.6 months (95%CI, 7.7 - 14.5 months), and median OS was not reached (95%CI, 19.2 - not estimable). Adverse events of grade 3 or higher occurred in 77.1% of the patients, and the safety profile of this combination was consistent with previously reported safety profile of the individual medicines.

Conclusions

In previously untreated advanced TC, the addition of atezolizumab to carboplatin and paclitaxel showed higher efficacy compared to historical controls, with a manageable safety profile. These results suggest that atezolizumab plus carboplatin and paclitaxel could become a new standard treatment option for patients with previously untreated advanced or metastatic TC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Chugai Pharmaceutical.

Disclosure

T. Mimori: Financial Interests, Personal, Invited Speaker: AstraZeneca, Taiho pharmaceutical, Chugai pharmaceutical, Bristol Myers Squibb, Daiichi Sankyo pharmaceutical, Eisai; Financial Interests, Personal, Local PI: Amgen, MSD, Janssen Pharmaceutical, Syneos Health. T. Shukuya: Financial Interests, Personal, Local PI: AstraZeneca, Chugai pharmaceutical, MSD; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Eli Lilly, Ono Pharmaceutical, Merck, Novartis, Takeda pharmaceutical, Pfizer, Daiichi Sankyo pharmaceutical, Taiho pharmaceutical, Bristol Myers Squibb, Eisai, Nippon Kayaku, Amgen. Y. Goto: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, Guardant Health Inc., MSD, Novartis, Ono Pharmaceutical, Pfizer, Taiho, Johnson and Johnson, D3bio; Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, MSD, Merck, Novartis, Ono Pharmaceutical, Pfizer, Taiho, Thermo Fischer; Financial Interests, Personal, Other, Travel Grant: Daiichi Sankyo; Financial Interests, Institutional, Local PI: Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly; Financial Interests, Personal and Institutional, Coordinating PI: Chugai, Novartis, Pfizer; Financial Interests, Institutional, Coordinating PI: Guardant Health; Financial Interests, Personal and Institutional, Local PI, NA: Preferred Network; Financial Interests, Institutional, Other, NA: IQVIA; Financial Interests, Institutional, Funding, NA: MSD, AstraZeneca; Financial Interests, Institutional, Funding: Astellas Pharma, AbbVie, Amgen, Syneos, Sysmex, CMIC, Bayer Pharm, MedPace, Janssen Pharma, Ono Pharm, Takeda, Clinical Research Support Center Kyushu, SATOMI; Non-Financial Interests, Personal, Member of Board of Directors: Cancer Net Japan, JAMT. T. Asao: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Chugai pharmaceutical, Daiichi Sankyo pharmaceutical, Eli Lilly, Merck, MSD, Nippon Kayaku, Ono Pharmaceutical, Pfizer, Taiho pharmaceutical, Takeda pharmaceutical. K. Takayama: Financial Interests, Personal, Invited Speaker, Sponsor/Funding: AstraZeneca, Chugai Pharmaceutical, Eli Lilly; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, MSD, Ono Pharmaceutical, Merck, Novartis. K. Kaira: Financial Interests, Personal and Institutional, Invited Speaker, Funding: AstraZeneca; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, Boehringer Ingelheim, Ono pharmaceutical, Takeda pharmaceutical, Bristol Myers Squibb; Financial Interests, Institutional, Funding: Daiichi Sankyo pharmaceutical. H. Tanaka: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai pharmaceutical, Boehringer Ingelheim, Eli Lilly, MSD, Ono Pharmaceutical, Merck, Novartis, Takeda pharmaceutical, Pfizer, Daiichi Sankyo pharmaceutical, Taiho pharmaceutical, Bristol Myers Squibb, Eisai, Hisamitsu pharmaceutical, Nippon Kayaku; Financial Interests, Institutional, Local PI: Chugai pharmaceutical, Merck, AstraZeneca, MSD, Eli Lilly, Ono Pharmaceutical, Bristol Myers Squibb, Takeda pharmaceutical, Taiho pharmaceutical, Pfizer, Daiichi Sankyo pharmaceutical, AbbVie, Amgen, Janssen pharmaceutical. R. Ko: Financial Interests, Personal and Institutional, Invited Speaker, Funding: AstraZeneca; Financial Interests, Personal, Invited Speaker: Chugai parmaceutical, Daiichi Sankyo pharmaceutical, Eli Lilly, Ono Pharmaceutical, Taiho pharmaceutical, Takeda pharmaceutical; Financial Interests, Personal, Invited Speaker, Funding: MSD. M. Tachihara: Financial Interests, Personal, Invited Speaker: Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K, MSD K.K., Ono Pharmaceutical Co., Ltd., Bristol Myers Squibb Co. Ltd., Nippon Boehringer Ingelheim Co., Ltd., Pfizer Japan Inc., Daiichi Sankyo, Janssen Pharmaceutical K.K., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd.; Financial Interests, Institutional, Research Grant: AstraZeneca K.K., Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd. T. Suzuki: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim. J. Tanizaki: Financial Interests, Personal, Invited Speaker: Boehringer-Ingelheim Japan Inc, Bristol Myers Squibb Co. Ltd, Chugai Pharmaceutical Co., Ltd, Daiichi Sankyo Co., Ltd, Eli Lilly Japan K.K, Janssen Pharmaceutical K.K, MSD K.K, Nihon Medi-Physics Co., Ltd., Nippon Kayaku Co., Ltd., Taiho Pharmaceutical Co. Ltd. K, Ono Pharmaceutical Co. Ltd, Pfizer Japan Inc, AstraZeneca K.K., Takeda Pharmaceuticals; Financial Interests, Personal, Advisory Board: AstraZeneca K.K., AbbVie GK, Genmab, Taiho Pharmaceutical Co. Ltd. K, Daiichi Sankyo Co., Ltd; Non-Financial Interests, Personal, Member: ASCO, JSMO, Japan Lung Cancer Society, ESMO, IASLC. S. Sugawara: Financial Interests, Personal, Other, Lecture fee: AstraZeneca, Chugai Pharma, Nippon Boehringer Ingelheim, Taiho Pharmaceutical, Pfizer, Lilly, Novartis, Bristol Myers Squibb, Ono Pharmaceutical, MSD K.K, Kyowa Kirin, Takeda, Nippon Kayaku, Merck, Amgen, Thermo Fisher Scientific; Financial Interests, Personal, Other, Lecture Fee: Eisai, Sysmex; Financial Interests, Institutional, Local PI: AstraZeneca, Chugai Pharma, MSD K.K, Daiichi Sankyo, Bristol Myers Squibb, AnHeart, Ono Pharmaceutical, Nippon Boehringer Ingelheim, AbbVie, Parexel International, Amgen, Taiho Pharmaceutical, Accerise, A2 Healthcare, EPS Corporation, Syneos Health, PPD-SNBL. Y. Zenke: Financial Interests, Personal, Invited Speaker, Funding: AstraZeneca, Chugai Pharmaceutical, MSD, Daiichi Sankyo pharmaceutical, Amgen; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Eli Lilly, Ono Pharmaceutical, Novartis, Takeda pharmaceutical, Pfizer, Taiho Pharmaceutical, Bristol Myers Squibb, Nippon Kayaku; Financial Interests, Personal, Funding: Merck. K. Mori: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, Eli Lilly Japan, Chugai Pharma. K. Takahashi: Non-Financial Interests, Personal, Other: Amgen, Eli Lilly, Merck, Novartis Pharma K. K.; Financial Interests, Personal, Invited Speaker: AstraZeneca, BioMerieux Japan Ltd., Bristol Myers Squibb, Daiichi Sankyo pharmaceutical, MSD, Ono Pharmaceutical, Pfizer; Financial Interests, Personal and Institutional, Invited Speaker, Research Grant: Boehringer Ingelheim, KYORIN Pharmaceutical Co, Ltd; Financial Interests, Personal and Institutional, Invited Speaker, Research Funding: Chugai pharmaceutical; Financial Interests, Personal, Invited Speaker, Research Funding: Nippon Kayaku; Financial Interests, Institutional, Research Funding: Taiho pharmaceutical; Financial Interests, Personal, Leadership Role: Takeda pharmaceutical; Financial Interests, Institutional, Funding, Imstituitional: Teijin Phrama Limited. All other authors have declared no conflicts of interest.