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.

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/m 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.