A Phase Ib Study of the Simmitecan Single Agent and in Combination With 5-Fluorouracil/Leucovorin or Thalidomide in Patients With Advanced Solid Tumor
- Front Pharmacol. 2022 Jul 22:13:833583. doi: 10.3389/fphar.2022.833583.
- 1. Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
- 2. Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
- 3. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), National Drug Clinical Trial Center, Peking University Cancer Hospital and Institute, Beijing, China.
- 4. Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
- 5. Haihe Biopharma Co., Ltd., Shanghai, China.
Background: Simmitecan is a potent inhibitor of Topoisomerase I with anti-tumor activity. This phase Ib trial was conducted to investigate the safety and anti-tumor effect of simmitecan alone or in combination with other drugs. Methods: Eligible patients with advanced solid tumor had no further standard treatment options. Patients were allocated to receive simmitecan alone, simmitecan in combination with 5-fluorouracil (5-FU)/leucovorin (LV), or simmitecan in combination with thalidomide, 14 days a cycle, until disease progression or unacceptable toxicity occurred. Results: A total of 41 patients were enrolled, with a median age of 55 (range 29-69) years. Among them, 13 patients received simmitecan monotherapy, 10 received simmitecan + 5-FU/LV, and 18 received simmitecan + thalidomide. No dose-limiting toxicity occurred. Overall, the most common grade 3/4 adverse event (AE) was neutropenia (46.2, 70.0, and 88.9%, respectively, in simmitecan, simmitecan + 5-FU/LV, and simmitecan + thalidomide cohorts), and treatment-related severe AEs included anemia and febrile neutropenia (7.7% each in simmitecan cohort), diarrhea (10% in simmitecan +5-FU/LV cohort), and febrile neutropenia (5.6% in simmitecan + thalidomide cohort). The majority of patients (24/41, 58.3%) had progressed on prior irinotecan; nevertheless, partial response was achieved in one Colorectal Cancer patients treated with simmitecan + thalidomide. The disease control rates of simmitecan, simmitecan + 5-FU/LV, and simmitecan + thalidomide cohorts were 46.2, 80.0, and 61.1%, respectively. Conclusion: This study demonstrated a manageable safety profile of simmitecan as a single agent or as part of a combination therapy. There have not been any safety concerns with simmitecan in combination when compared to simmitecan alone. Simmitecan + 5-FU/LV regimen seemed to have a better efficacy. Nonetheless, the efficacy of this regimen needs to be further explored in the subsequent study.