Breakthrough Clinical Results
Taiho Oncology announced new data to be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. Highlights include data on a potential all-oral therapy for acute myeloid leukemia (AML) combining decitabine, cedazuridine, and venetoclax, showing promising complete remission rates and median overall survival. Positive safety and efficacy results were also reported for zipalertinib, an investigational drug for non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, meeting its primary endpoint of overall response rate in the Phase 2b REZILIENT1 study. Additionally, data from three real-world studies of FDA-approved therapies will be presented.
Key Highlights
- Potential all-oral regimen for AML (decitabine, cedazuridine, and venetoclax) shows high complete remission rates.
- Zipalertinib demonstrates positive efficacy and safety in NSCLC patients with EGFR exon 20 insertion mutations, meeting primary endpoint.
- Data from three real-world studies of FDA-approved therapies will be presented.
- Zipalertinib received Breakthrough Therapy Designation from the FDA.
Recent Studies
Recent Studies for Acute Myeloid Leukemia: Interventions and Outcomes
Study on Non-Promyelocytic AML
A recent study focused on the treatment of non-promyelocytic acute myeloid leukemia (non-PML AML) using pioglitazone (a dual peroxisome-proliferator activated receptor PPARα/γ agonist) combined with transcriptional modulators.
Key outcomes: * Complete remission (CR) was achieved in relapsed/refractory (r/r) non-PML AML * Pioglitazone was integrated with differentially designed editing schedules * Treatment facilitated induction of tumor cell death * PPARα/γ agonists provided tumor-type agnostic biomodulatory efficacy
Study on Hypomethylating Agents
A significant study examined hypomethylating agents (HMAs) in patients with relapsed or primary treatment-refractory (RR-AML) acute myeloid leukemia.
Interventions: * 655 patients received either azacitidine (57%) or decitabine (43%)
Key outcomes: * Best responses were complete remission (CR; 11%) or CR with incomplete count recovery (CRi; 5.3%) * Additional 8.5% experienced hematologic improvement * Median overall survival (OS) was 6.7 months * Patients achieving CR and CRi had median OS of 25.3 and 14.6 months, respectively * Presence of ≤5% circulating blasts and a 10-day schedule of decitabine were associated with improved response rates * 16% of RR-AML patients achieved CR/CRi with HMAs and experienced median OS of 21 months
Mcl-1 Targeting Study
A molecular study targeted Mcl-1 (myeloid cell leukemia-1) with small interference RNA (siRNA) in acute myeloid leukemia cell line HL-60.
Intervention approach: * siRNA transfection performed with a liposome approach
Key outcomes: * Transfection with siMcl-1 significantly suppressed Mcl-1 mRNA and protein expression in a time-dependent manner * Results showed strong growth inhibition and spontaneous apoptosis * Pretreatment with siMcl-1 synergistically enhanced the cytotoxic effect of etoposide * Mcl-1 down-regulation significantly increased apoptosis sensitivity to etoposide
These studies represent important advances in the treatment approaches for acute myeloid leukemia, targeting different molecular mechanisms and providing valuable insights into potential therapeutic strategies for this challenging disease.
Drug used in other indications
Decitabine, Cedazuridine and Venetoclax Trials Beyond Acute Myeloid Leukemia
Additional Indications
Decitabine/cedazuridine and venetoclax combination therapy is currently being trialled for indications beyond Acute myeloid leukemia, specifically:
- Myelodysplastic syndromes (MDS)
- Chronic myelomonocytic leukemia (CMML)
For MDS: * Venetoclax is currently being evaluated in clinical trials as a monotherapy in high-risk myelodysplastic syndromes * Oral hypomethylating agents including cedazuridine-decitabine (C-DEC) have been approved for MDS
For CMML: * Hypomethylating agents including oral decitabine/cedazuridine have been US FDA approved for CMML management * Overall response rates of 40-50% and complete remission rates of <20% with hypomethylating agents
Intervention Models
The intervention models for these trials include:
- Total-oral therapy combinations using an oral HMA 'backbone' are in early phases of clinical development
- Clinical trials are employing these agents to identify optimal regimens that deliver effective disease-directed therapy with good tolerability
- The goal is to develop all-oral therapies that are convenient and efficacy-equivalent for patients with HR-MDS or AML
These clinical trials aim to establish treatment options that maintain effectiveness while improving the patient experience through oral administration routes.