Kyle Doherty

Key Takeaways Exceptional-responder profiling identified TAM gene upregulation (e.g., CD206, CD163) in long-term responders, paired with interferon-γ, TNF-α/NF-κB, and antigen-presentation enrichment across tumor and immune compartments. Cancer-cell CD24 expression was consistently higher in primary progressors and independently associated with poorer outcomes across validation TMAs, while CD47 expression did not correlate with PD-1 resistance. Spatial and multiplex analyses showed increased CD14+ TAM density proximate to tumor cells in long-term responders, suggesting macrophage contexture and function, not simply abundance, may predict durable benefit. In advanced RET+ NSCLC, ~41% required RET-TKI dose reductions (≤75% FDA dose), most often for laboratory toxicities, without statistically significant detriment in PFS, CNS progression, or time to next therapy. Real-world dosing patterns and chronic low-grade toxicity burden highlight the rationale for Project Optimus–aligned development toward optimal biological dosing rather than maximum tolerated dose. SHOW MORE

Key Takeaways B7-H4 overexpression in ovarian and endometrial cancers and potential immunosuppressive signaling support ADC targeting and rational combinations with immune checkpoint blockade. At 5.8 mg/kg in PROC (n=34), Mo‑Rez achieved 62% confirmed ORR with 1.4‑month median TTR; 4.8 and 2.8 mg/kg produced 53% and 31%. Endometrial cancer responses appeared dose dependent, with 67% ORR at 4.8 mg/kg (n=12) versus 9% at 2.8 mg/kg (n=11). Safety was characterized by frequent any‑grade TRAEs and dose-related grade ≥3 cytopenias/GI events; discontinuations were uncommon, and ocular toxicity or ILD signals were not prominent. BEHOLD‑2 evaluates Mo‑Rez plus dostarlimab in MMRp/MSS endometrial cancer and Mo‑Rez with or without bevacizumab in relapsed ovarian/fallopian/peritoneal cancers, prioritizing DLTs then confirmed ORR. SHOW MORE

Adanma Ayanambakkam, MD, MS, discusses findings from the FIT-001 trial of darlifarnib plus cabozantinib in RCC.

Cathy Eng, MD, FACP, FASCO, discusses how oncology fellows can navigate the journal submission and review process.

The regulatory path to approval for RP1 plus nivolumab in anti–PD-1–pretreated melanoma ran through 3 BLAs, 2 CRLs, and a divided advisory committee vote.

The MAPKeeper-301 trial is evaluating frontline atebimetinib plus chemotherapy vs standard chemotherapy in metastatic pancreatic ductal adenocarcinoma.

Genetic testing decisions in patients with cancer may be affected by significant out-of-pocket costs.

The NCCN updated its guidelines to clarify the role of ctDNA as a biomarker for recurrence risk in colon and rectal cancer and for disease monitoring in Merkel cell carcinoma.

Patients with head and neck squamous cell carcinoma continued to displayed a survival benefit with pembrolizumab at a 4-year follow-up.