The Targeted Pulse: FDA Milestones and Heme Updates

Welcome to this week’s edition of The Targeted Pulse, our top 5 stories delivered right to you. This week, we saw FDA decisions in ovarian and lung cancers, as well as advancements in myelodysplastic syndromes (MDS) and myelofibrosis. From regulatory designations for promising new drugs to crucial clinical trials, here are the top stories that shaped the week.

FDA Approves Pembrolizumab Combo for Recurrent Ovarian Cancer

The FDA approved pembrolizumab (Keytruda) in combination with paclitaxel, with or without bevacizumab (Avastin), for patients with platinum-resistant recurrent ovarian cancer whose tumors express PD-L1 (CPS ≥1). This decision, supported by the phase 3 KEYNOTE-B96 trial, marks a significant milestone as the first immunotherapy regimen to demonstrate an overall survival (OS) benefit in this difficult-to-treat population.

Results showed the combination reduced the risk of death by 24% compared with chemotherapy alone, extending median OS to 18.2 months. Along with improved progression-free survival, the approval introduces a new biomarker-guided treatment paradigm for patients with limited options.

FDA Grants RMAT Designation to Inhalable Gene Therapy for Advanced Lung Tumors

The FDA granted regenerative medicine advanced therapy (RMAT) designation to KB707, an investigational inhaled gene therapy for advanced or metastatic non–small cell lung cancer (NSCLC). Developed by Krystal Biotech, KB707 uses a modified HSV vector to deliver IL-2 and IL12 directly to lung tumors, localizing treatment to minimize systemic toxicity.

The designation follows promising phase 1/2 KYANITE-1 trial data, which showed a 27% objective response rate in heavily pretreated patients. RMAT status will expedite KB707’s development through intensive FDA guidance and eligibility for priority review, addressing a critical unmet need in refractory lung cancer.

Orca-T Shows Improved Survival Rates Over SOC in MDS

Recent post-hoc data presented at the 2026 Transplantation & Cellular Therapy Meetings demonstrate that Orca-T significantly improves survival rates for patients with MDS compared to the standard of care. In a focused analysis of patients receiving myeloablative, HLA-matched transplants, Orca-T achieved a remarkable 100% OS rate at 3 years, whereas the standard posttransplant cyclophosphamide cohort saw only 62%.

Additionally, Orca-T reduced non-relapse mortality to 0% and improved 1-year relapse-free survival to 95%. These results suggest Orca-T could redefine transplantation for high-risk MDS, pending confirmation from the ongoing phase 3 Precision-T trial.

Dual Antibodies Beat Single for Type 1 CALR-Mutant Myelofibrosis

New research published in Blood reveals that dual monoclonal antibody therapy is more effective than single-agent treatment for type 1 CALR-mutant myelofibrosis. By targeting distinct epitopes on the mutant calreticulin protein, the combination superiorly blocks oncogenic signaling and eradicates primary patient-derived megakaryocyte progenitors. In xenograft models, this dual approach improved survival and overcame resistance to ruxolitinib.

Conversely, type 2 mutations showed partial resistance to antibodies due to increased protein dimerization, suggesting a need for different strategies like triple-combination therapies. These findings highlight a shift toward ultra-precision medicine, where treatment is tailored specifically to a patient’s CALR mutation class.

New Frontiers in Targeted Therapy for Rare Lung Cancer Alterations

Bruna Pellini, MD, explores the evolving treatment landscape for rare genomic alterations in NSCLC, emphasizing the transformative impact of next-generation targeted therapies. Key advancements include highly potent, central nervous system-penetrant inhibitors for ALK,ROS1 , and HER2 mutations, which have significantly extended survival and improved intracranial responses compared to older agents.

The discussion highlights the shift toward precision medicine, where specific biomarker identification through comprehensive genomic testing is essential. By addressing rare drivers that once had limited options, these novel drugs provide long-term disease control, redefining standard care for molecularly defined patient subsets.