117TiP A phase II study of toripalimab combined with paclitaxel/carboplatin for the first-line treatment of advanced thymic carcinoma

Abstract

BackgroundThymic epithelial tumors (TETs) include thymomas (Ts) and thymic carcinomas (TCs), with an annual incidence of about 1.7/million, and TCs account for about 15% to 20% of TETs. Compared with Ts, TCs are more aggressive with poor prognosis. For advanced TCs, systemic chemotherapy is an important treatment, and the most common regimen is carboplatin combined with paclitaxel. However, the efficacy of chemotherapy is poor. The result of one study showed that objective response rate (ORR) was 36% and median progression-free survival (mPFS) was 7.5 months. Studies have shown that programmed cell death ligand 1 (PD-L1) is highly expressed in TC, which means that anti-programed death-1 (PD-1)/PD-L1 therapy will be a reasonable option for patients (pts) with TC. Giaccone and colleges carried out a single-arm phase II study where pts with recurrent TC received pembrolizumab monotherapy. Among 40 evaluable pts, an ORR of 22.5% was observed and mPFS was 4.2 months. In addition, the potential immunogenic effects of chemotherapy may enhance the efficacy of immunotherapy. Hence, PD-1/PD-L1 inhibitors combined with chemotherapy regimens may improve the treatment response of TC and prolong the overall survival of pts. However, the clinical data are lacking.Trial DesignThis is a prospective phase II trial aiming at evaluating the efficacy of a PD-1 inhibitor, toripalimab, in combination with paclitaxel/carboplatin in the first-line treatment of pts with advanced TC. Enrolled pts will receive toripalimab (240mg, d1) in combination with paclitaxel (175mg/m2, d1) and carboplatin (AUC=5, d1), q3w, for 6 cycles. After that, those pts whose disease did not progress will continue the treatment with toripalimab (240mg, d1, q4w) until disease progression, intolerable toxicity, or withdrawal by the pts request. Key inclusion criteria: pts aged ≥18 years, ECOG≤2, Histologically or cytologically confirmed Masaoka stage III or IV TC, without prior system anticancer therapy after diagnosed with this disease, adequate organ function. Primary end point: PFS. secondary end points: ORR, duration of response (DOR), Disease control rate (DCR), overall survival (OS), time to response (TTR) and safety.Clinical trial identificationChiCTR2000039155.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest. BackgroundThymic epithelial tumors (TETs) include thymomas (Ts) and thymic carcinomas (TCs), with an annual incidence of about 1.7/million, and TCs account for about 15% to 20% of TETs. Compared with Ts, TCs are more aggressive with poor prognosis. For advanced TCs, systemic chemotherapy is an important treatment, and the most common regimen is carboplatin combined with paclitaxel. However, the efficacy of chemotherapy is poor. The result of one study showed that objective response rate (ORR) was 36% and median progression-free survival (mPFS) was 7.5 months. Studies have shown that programmed cell death ligand 1 (PD-L1) is highly expressed in TC, which means that anti-programed death-1 (PD-1)/PD-L1 therapy will be a reasonable option for patients (pts) with TC. Giaccone and colleges carried out a single-arm phase II study where pts with recurrent TC received pembrolizumab monotherapy. Among 40 evaluable pts, an ORR of 22.5% was observed and mPFS was 4.2 months. In addition, the potential immunogenic effects of chemotherapy may enhance the efficacy of immunotherapy. Hence, PD-1/PD-L1 inhibitors combined with chemotherapy regimens may improve the treatment response of TC and prolong the overall survival of pts. However, the clinical data are lacking. Thymic epithelial tumors (TETs) include thymomas (Ts) and thymic carcinomas (TCs), with an annual incidence of about 1.7/million, and TCs account for about 15% to 20% of TETs. Compared with Ts, TCs are more aggressive with poor prognosis. For advanced TCs, systemic chemotherapy is an important treatment, and the most common regimen is carboplatin combined with paclitaxel. However, the efficacy of chemotherapy is poor. The result of one study showed that objective response rate (ORR) was 36% and median progression-free survival (mPFS) was 7.5 months. Studies have shown that programmed cell death ligand 1 (PD-L1) is highly expressed in TC, which means that anti-programed death-1 (PD-1)/PD-L1 therapy will be a reasonable option for patients (pts) with TC. Giaccone and colleges carried out a single-arm phase II study where pts with recurrent TC received pembrolizumab monotherapy. Among 40 evaluable pts, an ORR of 22.5% was observed and mPFS was 4.2 months. In addition, the potential immunogenic effects of chemotherapy may enhance the efficacy of immunotherapy. Hence, PD-1/PD-L1 inhibitors combined with chemotherapy regimens may improve the treatment response of TC and prolong the overall survival of pts. However, the clinical data are lacking. Trial DesignThis is a prospective phase II trial aiming at evaluating the efficacy of a PD-1 inhibitor, toripalimab, in combination with paclitaxel/carboplatin in the first-line treatment of pts with advanced TC. Enrolled pts will receive toripalimab (240mg, d1) in combination with paclitaxel (175mg/m2, d1) and carboplatin (AUC=5, d1), q3w, for 6 cycles. After that, those pts whose disease did not progress will continue the treatment with toripalimab (240mg, d1, q4w) until disease progression, intolerable toxicity, or withdrawal by the pts request. Key inclusion criteria: pts aged ≥18 years, ECOG≤2, Histologically or cytologically confirmed Masaoka stage III or IV TC, without prior system anticancer therapy after diagnosed with this disease, adequate organ function. Primary end point: PFS. secondary end points: ORR, duration of response (DOR), Disease control rate (DCR), overall survival (OS), time to response (TTR) and safety. This is a prospective phase II trial aiming at evaluating the efficacy of a PD-1 inhibitor, toripalimab, in combination with paclitaxel/carboplatin in the first-line treatment of pts with advanced TC. Enrolled pts will receive toripalimab (240mg, d1) in combination with paclitaxel (175mg/m2, d1) and carboplatin (AUC=5, d1), q3w, for 6 cycles. After that, those pts whose disease did not progress will continue the treatment with toripalimab (240mg, d1, q4w) until disease progression, intolerable toxicity, or withdrawal by the pts request. Key inclusion criteria: pts aged ≥18 years, ECOG≤2, Histologically or cytologically confirmed Masaoka stage III or IV TC, without prior system anticancer therapy after diagnosed with this disease, adequate organ function. Primary end point: PFS. secondary end points: ORR, duration of response (DOR), Disease control rate (DCR), overall survival (OS), time to response (TTR) and safety. Clinical trial identificationChiCTR2000039155. ChiCTR2000039155. Legal entity responsible for the studyThe authors. The authors. FundingHas not received any funding.