FDA Approves Belzutifan as First Oral Treatment for Advanced Pheochromocytoma and Paraganglioma
• The FDA has approved belzutifan (Welireg) for adult and pediatric patients 12 years and older with locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma, based on promising phase 2 trial results.
• As a selective HIF-2α inhibitor, belzutifan demonstrated a 26% overall response rate with a median duration of response of 20.4 months, offering a novel mechanism of action compared to historically used treatments.
• This approval is particularly significant as previous treatment options were limited, with the only previously approved agent no longer commercially available and alternative therapies associated with concerning toxicity profiles.
Kura Oncology Initiates Phase 1 Trial Combining Ziftomenib with Imatinib for Advanced GIST Treatment
• Kura Oncology has dosed first patients in KOMET-015, a Phase 1 trial evaluating ziftomenib in combination with imatinib for advanced gastrointestinal stromal tumors (GIST) after imatinib failure.
• Preclinical studies show the combination provides robust antitumor activity in both imatinib-sensitive and imatinib-resistant GIST models through a synthetic lethal mechanism targeting tumor vulnerabilities.
• With approximately 60% of GIST patients developing imatinib resistance within two years, this novel menin inhibitor combination represents a potential breakthrough for the estimated 4,000-6,000 new GIST cases diagnosed annually in the U.S.
CT Imaging Predicts Surgical Benefits of Neoadjuvant TKI Therapy in Non-Metastatic GIST Patients
• New research demonstrates that CT imaging can accurately predict surgical benefits of neoadjuvant TKI treatment in non-metastatic GIST patients within 3 months of treatment initiation.
• Study shows 22 out of 39 GIST patients experienced surgical benefits from neoadjuvant TKI therapy, leading to less invasive procedures and better organ preservation.
• Patients who benefited showed significant tumor volume reduction above 66% within three months, with a median neoadjuvant treatment interval of 8.3 months.
GSK Acquires IDRx for $1 Billion to Advance GIST Treatment
• GSK has agreed to acquire IDRx for $1 billion upfront, plus $150 million in potential milestone payments, to enhance its gastrointestinal cancer portfolio.
• The acquisition brings IDRX-42, a selective KIT tyrosine kinase inhibitor, which targets key mutations in gastrointestinal stromal tumors (GIST).
• IDRX-42 has shown promising anti-tumor activity in Phase I/Ib trials, particularly in patients with GIST who have developed resistance to existing therapies.
• GSK aims to accelerate the development of IDRX-42 in 2025, potentially redefining the treatment landscape for GIST patients with limited options.
Olverembatinib's New Indication for CML-CP Included in China's NRDL
• Olverembatinib's new indication for chronic-phase chronic myeloid leukemia (CML-CP) resistant and/or intolerant to first- and second-generation TKIs has been included in China's National Reimbursement Drug List (NRDL).
• The inclusion, effective January 1, 2025, expands olverembatinib's accessibility to a broader population of CML patients in China, reaffirming its importance as an innovative treatment option.
• Olverembatinib, a third-generation BCR-ABL inhibitor, targets BCR-ABL and its mutants, including T315I, addressing TKI resistance, a significant challenge in CML treatment.
• Ascentage Pharma and Innovent Biologics jointly commercialize olverembatinib in China, aiming to ensure rapid rollout of expanded insurance coverage and improve patient access.
FDA Approves Imkeldi (Imatinib) Oral Solution for Certain Leukemias and Cancers
• The FDA has approved Imkeldi (imatinib) oral solution, the first liquid formulation of imatinib, for treating certain forms of leukemia and other cancers.
• Imkeldi is indicated for chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS), and gastrointestinal stromal tumors (GIST) in adults and children.
• The oral solution offers precise dosing, a palatable strawberry flavor, and does not require refrigeration, improving adherence and accessibility for patients.
• This approval marks Shorla Oncology's fourth FDA approval, advancing its mission to improve existing oncology treatments through formulation re-innovation.
Kura Oncology and Kyowa Kirin Collaborate to Advance Ziftomenib for AML Treatment
• Kura Oncology and Kyowa Kirin have entered a global strategic collaboration to develop and commercialize ziftomenib, targeting AML and other hematologic malignancies.
• Kura will receive $330 million upfront and up to $420 million in near-term milestones, with potential for $1.161 billion in total milestone payments.
• Kura will lead US development and commercialization, sharing profits and losses equally with Kyowa Kirin, while Kyowa Kirin will lead ex-US efforts.
• Ziftomenib, a menin inhibitor, has Breakthrough Therapy Designation for R/R NPM1-mutant AML, with NDA submission anticipated in 2025.
Ziftomenib Shows Promise in AML: Kura Oncology and Kyowa Kirin Advance to Phase 3 Trials
• Kura Oncology and Kyowa Kirin's ziftomenib demonstrates statistically significant efficacy in Phase 2 trial for relapsed/refractory NPM1-mutant acute myeloid leukemia (AML).
• The companies plan to submit a New Drug Application (NDA) to the FDA in the second quarter of 2025, seeking approval for ziftomenib in R/R NPM1-m AML.
• Phase 3 trials are set to begin in the second half of 2025, evaluating ziftomenib in combination with intensive and non-intensive chemotherapy regimens for newly diagnosed AML.
• FDA feedback supports potential accelerated approval pathways in both intensive and non-intensive treatment settings, based on MRD negative CR and CR endpoints.
Kura Oncology Announces Q3 2024 Financial Results and Pipeline Updates
• Kura Oncology anticipates topline results from the ziftomenib registration-directed trial for relapsed/refractory NPM1-mutant AML in early 2025.
• Data from 100 patients in the Phase 1a study of ziftomenib will be presented at the ASH Annual Meeting in December 2024, showcasing its safety and activity.
• A Phase 1b expansion study of ziftomenib is enrolling patients at a 600 mg dose across all cohorts, with preliminary data expected in 2025.
• Kura's cash reserves of $455.3 million are projected to fund operations into 2027, supporting ongoing clinical trials and research initiatives.
Precision Medicine Framework Improves Treatment Strategies for GIST and Sarcoma
• A novel framework analyzes observational and RCT data to optimize treatment decisions in gastrointestinal stromal tumors (GIST).
• The framework identifies patient subgroups benefiting from adjuvant imatinib, balancing undertreatment and overtreatment risks.
• In soft tissue sarcoma, the framework refines radiotherapy recommendations, potentially sparing 15% of patients from unnecessary treatment.
• The framework demonstrates robustness across various clinical scenarios, enhancing personalized medicine approaches.
GIST and Genome & Company Identify CNTN4 as Novel Immuno-Oncology Target
• GIST and Genome & Company researchers identified CNTN4 as a novel target that inhibits T cell proliferation and cytokine secretion, crucial for immune response against cancer.
• The team developed GENA-104, an antibody that inhibits CNTN4, restoring T cell function and significantly reducing tumor growth in preclinical animal models.
• Analysis of clinical data suggests GENA-104 may be effective for patients who do not respond to existing immuno-oncology drugs, offering a new therapeutic avenue.
• This research validates GENA-104's potential and marks a significant step toward personalized cancer immunotherapy, with findings published in Science Immunity.
Adcendo's ADCE-D01 Receives FDA Clearance for Phase I/II Soft Tissue Sarcoma Trial
• Adcendo's ADCE-D01, a first-in-class antibody-drug conjugate (ADC) targeting uPARAP, has received FDA clearance for a Phase I/II trial in metastatic and/or unresectable soft tissue sarcoma (STS).
• The ADCElerate-01 trial will evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ADCE-D01 as a monotherapy in STS patients.
• uPARAP, the target of ADCE-D01, is highly overexpressed in mesenchymal cancers like STS, making it an attractive target for ADC development.
• The trial will recruit patients in the US and Europe, marking a significant step in developing new treatment options for STS with limited alternatives.
Fecal Microbiota Transplants Show Promise in Overcoming Immunotherapy Resistance in GI Cancers
• A South Korean study suggests fecal microbiota transplants (FMTs) may enhance immunotherapy efficacy in gastrointestinal (GI) cancer patients resistant to anti-PD-1 drugs.
• The study found that 46.2% of patients with metastatic solid tumors refractory to nivolumab benefited from FMTs, showing tumor shrinkage in some cases.
• Specific bacterial strains, like *Prevotella merdae*, improved FMT effectiveness, while others, such as *Lactobacillus salivarius*, had detrimental impacts.
• Researchers emphasize the need for efficient FMT production methods and further clinical trials to integrate FMT into standard cancer treatment.
Uninterrupted Imatinib Use Improves Outcomes in Advanced GIST
• A clinical trial reveals that continuous imatinib therapy significantly improves outcomes for patients with advanced gastrointestinal stromal tumors (GIST).
• Patients who discontinued imatinib experienced faster disease progression, shorter time to imatinib resistance, and decreased overall survival compared to those who continued treatment.
• The findings support current guidelines recommending uninterrupted imatinib treatment for advanced GIST patients who can tolerate the therapy's side effects.
• The study underscores the importance of long-term follow-up in cancer trials to understand the impact of treatment strategies on drug resistance and survival.
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