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1504 TQB3455 Plus Azacitidine in Patients with Newly Diagnosed, Mutant-IDH2 Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Phase 1 Trial

Program: Oral and Poster Abstracts
Session: 616. Acute Myeloid Leukemias: Investigational Drug and Cellular Therapies: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical trials, Clinical Research
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Wenbing Duan1*, Chunkang Chang, MD2*, Zhiguo Wang3*, Hongbing Ma4*, Min Ouyang5*, Xingli Zhao6*, Lifan Tu7*, Guodong Wu8*, Xunqiang Wang8*, Xiao Jun Huang9 and Hao Jiang10*

1Department of Hematology, Peking University People's Hospital, Beijing, China
2Hematology department, Shanghai Sixth People's Hospital, Shanghai Jiaotong University school of Medicine, Shanghai, China
3Harbin The First Hospital, Harbin, CHN
4West China Hospital, Sichuan University, Chengdu, China
5Peking University international Hospital, Beijing, China
6Department of Hematology, Oncology Center, Tianjin People's Hospital, No. 190 jieyuan Road, Hongqiao District,, Tianjin, China
7Chia Tai Tianqing Pharmaceutical Group Co., Ltd, Nanjing, AL, China
8Chia Tai Tianqing Pharmaceutical Group Co., Ltd, Nanjing, China
9Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
10Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China

Introduction:

TQB3455, a novel selective inhibitor of isocitrate dehydrogenase-2(IDH2) proteins, demonstrated well-tolerated and preliminary antitumor activity in relapsed/refractory acute myeloid leukemia(AML) and myelodysplastic syndromes(MDS). We evaluated the safety and efficacy of TQB3455 plus azacitidine in patients(pts) with newly diagnosed, mutant-IDH2 AML ineligible for intensive chemotherapy and MDS.

Methods:

This open-label, multicenter, phase 1 study enrolled AML or MDS pts with mIDH2. Eligible patients were 18 or older and had newly diagnosed, mutant-IDH2 AML and MDS, and an Eastern Cooperative Oncology Group performance status (ECOG) of 0–2. Pts received oral TQB3455 100 mg/day in continuous 28-day cycles, plus subcutaneous azacitidine 75 mg/m² per day for 7 days of each cycle. The primary endpoint was the overall response rate in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of the study drug.

Results:

Between June 3, 2022, and May 31, 2024, 21 pts were enrolled in the study and had received at least one dose of TQB3455, 17 were AML and 4 were MDS. The median age was 61 years and 47.6% were male, including 2 pts with ECOG 2. There were 12 pts with R140 mutation and 9 pts with R172 mutation. The most frequently mutated genes in whole pts were DNMT3A (52.4%), ASXL1 (23.8%), and WT1 (19.1%). Eight patients had poor-risk cytogenetics in AML pts. The median follow-up was 7.62 months (95%CI 4.63, 9.17).

Treatment was well tolerated in all pts. All pts experienced at least one treatment-emergent adverse event(TRAEs). The most common(≥20%) TRAEs were neutropenia (85.7%), leukopenia (66.7%), thrombocytopenia (66.7%), anemia (61.9%), white cell count increased (28.6%), pyrexia(23.8%). Grade 3 or higher TRAEs were neutropenia, leukopenia, thrombocytopenia, and anemia. The majority of these TRAEs could be recovered after supportive treatment. Serious treatment-related adverse events were reported in 8 (38.1%) pts, mainly pneumonia. Differentiation syndrome (DS) was not observed. Treatment-related deaths were reported in 1 AML pt.

For efficacy, an overall response was 94.1%, and 50.0% was achieved in AML pts and MDS pts. CR+CRi rates were 82.4% in AML pts, and the median duration of response and median event-free survival was not reached. The median time to complete remission plus complete remission with partial hematological was 2.79 months (95%CI, 1.25-2.79). Additionally, the CR rate was 50% in MDS pts. Among CR pts, two of them received hematopoietic stem-cell transplantation. The median OS was not reached in all pts.

Conclusion:

TQB3455 plus azacitidine was a well-tolerated, and effective therapy for newly diagnosed, mutant-IDH2 AML ineligible for intensive chemotherapy and MDS. The randomized study will be launched soon to explore the superiority of the therapy.

Disclosures: Tu: Chia Tai Tianqing Pharmaceutical Group Co., Ltd: Current Employment. Wu: Chia Tai Tianqing Pharmaceutical Group Co., Ltd: Current Employment. Wang: Chia Tai Tianqing Pharmaceutical Group Co., Ltd: Current Employment.

*signifies non-member of ASH