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Toripalimab and chidamide demonstrated particularly notable efficacy outcomes in well-differentiated liposarcoma and dedifferentiated liposarcoma.
Treatment with the combination of toripalimab-tpzi (Loqtorzi) and chidamide (Epidaza; Hiyasta) led to responses and encouraging progression-free survival (PFS) outcomes in patients with advanced or metastatic sarcoma, particularly in those with well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS), according to data from a phase 2 trial (NCT04025931) conducted in China.1
Data presented at the
In those with WDLPS or DDLPS (n = 24), the ORR and DCR 62.5% and 95.8%, respectively. Among those with non-WDLPS or -DDLPS (n = 45), these respective rates were 13.3% (P < .001) and 62.2%.
“The safety profile of this regimen was manageable, [and these data support] further clinical evaluation in phase 3, randomized studies,” lead study author Xing Zhang, MD, PhD, said in a presentation of the data. Zhang is a professor and a chief physician of the Department of Immunotherapy and Medical Oncology of Melanoma and Sarcoma at Sun Yat-sen University Cancer Center in Guangzhou, China.
Sarcomas—particularly liposarcomas—have been associated with HDAC gene amplifications. Additionally, Zhang noted that chidamide has demonstrated the ability to enhance the efficacy of immune checkpoint inhibitors and regulate immune response.
As such, this open-label, single-arm, multicenter phase 2 trial sought to evaluate the combination of the HDAC inhibitor chidamide and the PD-1 monoclonal antibody toripalimab in patients 14 to 70 years of age with confirmed advanced or metastatic sarcoma who had no standard therapy available or progressed on prior standard therapy.1,2
Patients needed to have adequate renal, hepatic, and hematologic function.1
Key exclusion criteria included any prior treatment with an HDAC or immune checkpoint inhibitor; any treatment with standard-of-care or investigational agents within 28 days of enrollment; known central nervous system metastases; and uncontrolled concurrent or psychiatric illness that could limit study compliance.
Enrolled patients received oral chidamide at 30 mg twice per week in combination with intravenous toripalimab at 240 mg once every 3 weeks. Treatment continued until disease progression or unacceptable toxicity.
ORR per RECIST 1.1 criteria served as the trial’s primary end point. PFS, overall survival (OS), DCR, and safety were secondary end points.
In the overall population (n = 73), patients had a median age of 47 years (range, 16-68), and the majority of patients were female (n = 40). Patients received a median of 2 prior treatment regimens (range, 0-5). Specifically, number of prior regimens included 0 (8.2%), 1 (35.6%), 2 (39.7%), 3 (11.0%), 4 (1.4%), and 5 (4.1%).
Disease histology of the enrolled population comprised leiomyosarcoma (28.8%), WDLPS/DDLPS (32.9%), myxoid/round cell liposarcoma (5.5%), undifferentiated sarcoma (8.2%), osteosarcoma (4.1%), Ewing’s sarcoma (2.7%), chondrosarcoma (1.4%), malignant peripheral nerve sheath tumor (1.4%), myxofibrosarcoma (2.7%), malignant solitary fibroma (1.4%), alveolar soft part sarcoma (2.7%), sclerosing epithelioid fibrosarcoma (1.4%), myofibroblastic sarcoma (1.4%), angiosarcoma (1.4%), and not otherwise specified (4.1%). Primary tumors sites included retroperitoneum/intra-abdomen (42.5%), viscera (27.4%), extremities (17.8%), trunk (5.5%), and head and neck (6.8%).
Findings showed patients in the overall efficacy-evaluable population achieved a median PFS of 7.1 months (95% CI, 4.0-10.2). However, when broken down by histology, those with WDLPS or DDLPS experienced a median PFS of 17.1 months (95% CI, 8.6-25.6) compared with 3.6 months (95% CI, 1.6-5.6) for those with non-WDLPS or -DDLPS (P < .001).
The median OS in the overall population was 36.0 months (95% CI, 20.8-51.2). However, the median OS was 43.0 months (95% CI, 34.1-51.9) in the WDLPS/DDLPS subgroup vs 24.4 months (95% CI, 23.0-25.8) in the non-WDLPS/DDLPS subgroup (P = .016).
The most common grade 1/2 treatment-related adverse effects (TRAEs) reported in the safety-evaluable population (n = 73) included anemia (53.4%), hypothyroidism (42.5%), leukopenia (32.9%), thrombocytopenia (30.1%), elevated creatinine levels (27.4%), neutropenia (24.6%), nausea/vomiting (23.3%), fatigue (15.1%), elevated transaminase levels (13.7%), reduced cortisol levels (12.3%), pruritus (11.0%), and fever (4.1%). The most common grade 3 or higher TRAEs comprised neutropenia (27.4%), thrombocytopenia (23.3%), leukopenia (15.1%), nausea/vomiting (9.6%), and anemia (1.4%).
Disclosures: Zhang did not declare any financial interests.
