The Targeted Pulse: FDA Decisions and Trial Breakthroughs
Key Takeaways
- JSKN003, an anti-HER2 ADC, receives FDA fast track status for platinum-resistant ovarian cancer, showing a 63% ORR and 7.7 months median PFS.
- Daraxonrasib, a RAS(ON) inhibitor, gains orphan drug designation for pancreatic cancer, with phase 1/1b trials showing 8.8 months median PFS.
Discover the latest breakthroughs in oncology, including FDA designations and promising trial results that could transform cancer treatment.
Welcome to this week's edition of The Targeted Pulse, your weekly wrap-up of the top developments in oncology. This week, we saw FDA breakthroughs, learned about care-changing trial data, and heard from expert clinicians in the field. From regulatory designations for promising new drugs to crucial clinical trials, here are the top stories that shaped the week.
FDA Fast Tracks Anti-HER2 Biparatopic ADC for Platinum-Resistant Ovarian Cancer
The FDA has granted fast track designation to JSKN003, a biparatopic anti-HER2 antibody-drug conjugate (ADC), for treating patients with advanced or metastatic platinum-resistant ovarian cancer (PROC). This status aims to accelerate the development and review of the drug, which addresses a significant unmet medical need due to the poor prognosis of PROC.
The designation is supported by pooled phase 1/2 clinical data showing a promising 63% objective response rate (ORR) and a median progression-free survival (PFS) of 7.7 months in patients with PROC. Notably, JSKN003 demonstrated efficacy across varying HER2 expression levels. The ADC's mechanism involves binding to 2 HER2 epitopes to selectively deliver a potent topoisomerase I inhibitor.
Daraxonrasib Earns FDA Orphan Drug Designation in Pancreatic Cancer
The FDA has granted orphan drug designation to daraxonrasib (RMC-6236), an oral, multiselective RAS(ON) inhibitor, for the treatment of pancreatic cancer. This designation recognizes the drug's potential to treat a rare disease and qualifies the developer for various incentives.
RAS driver mutations are present in nearly all pancreatic cancer cases, highlighting the need for targeted therapies. The designation is supported by promising safety and preliminary efficacy data from the phase 1/1b trial, which showed a median PFS of 8.8 months in patients with second-line metastatic pancreatic ductal adenocarcinoma with KRAS G12X mutations. Daraxonrasib is currently being investigated in a phase 3 trial against standard chemotherapy.
New Evidence Emerges on Narsoplimab’s Therapeutic Potential in TA-TMA
New data suggest that the investigational monoclonal antibody narsoplimab (OMS721) significantly reduces the risk of mortality in patients with high-risk hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA).
A comparative analysis of narsoplimab-treated cohorts vs an untreated control cohort showed an approximately 72% lower mortality risk for treated patients. The survival benefit was consistent across different analyses and particularly improved the 1-year survival rate in patients with risk factors such as elevated LDH, acute GVHD, organ dysfunction, and infection. TA-TMA is a serious complication with no currently approved treatment, and these findings support narsoplimab’s potential as a therapy, with its biologics license application currently under FDA review.
Dillon on Considerations for GLP-1s in the Neuroendocrine Tumor Space
Joseph Dillon, MD discusses the growing use of glucagon-like peptide 1 (GLP-1) receptor agonists (for diabetes and obesity) among patients with neuroendocrine tumors (NETs), noting that up to 6% of his clinic population uses them. While specific human data are lacking, there's a theoretical concern: some NETs express GLP-1 receptors. Preclinical studies show that GLP-1 agents can potentially stimulate the growth of these receptor-positive tumors. Key unanswered questions remain, including which human NETs express the receptor and whether this growth promotion translates from animal and in vitro models to clinical experience. Clinicians should be cautious and consider this potential risk, Dillon advises.
FDA Grants Breakthrough Therapy Status to Zenocutuzumab for Patients With NRG1 Fusion
The FDA granted breakthrough therapy designation to zenocutuzumab (Bizengri) for treating adults with advanced unresectable or metastatic cholangiocarcinoma harboring a neuregulin 1 (NRG1) gene fusion. This designation, which expedites development, was supported by promising data from the phase 2 eNRGy trial. Zenocutuzumab showed a 37% ORR and a median PFS of 9.2 months, with a clinical benefit rate of 58%. Most adverse events were grade 1 or 2 and remained consistent among the trial population. This offers a new targeted option for patients with this rare, aggressive, and hard-to-treat genomic driver.
