Panitumumab-based EGFR blockade drives 53.9% ORR in platinum-refractory renal medullary carcinoma

SMARCB1-deficient renal medullary carcinoma (RMC)—a rare, hypoxic medullary kidney cancer enriched in young patients of African descent with sickle cell trait—was historically treated with platinum-based chemotherapy (ORR ~29%, median OS ~13 months). In a prospective multi-institutional study, panitumumab-based EGFR blockade (wild-type EGFR dependency) delivered a 53.9% ORR with 15.4% complete responses in 26 heavily pretreated patients (96% platinum-refractory), a response rate well above the typical post-platinum expectation in RMC (generally low/near-zero with “garden-variety” RCC agents), and the group reports achieving their 2023 benchmark of doubling median survival to ~24 months by 2025. Safety-wise, the abstract flags a key “don’t do this” signal: prospective nivolumab + ipilimumab produced a 0% response rate with frequent hyperprogression (trial halted for futility), contrasting with its established activity in clear-cell RCC but underscoring that RMC biology is different; the program is also expanding antibody-based strategies to surface targets (MUC16/CA-125, TROP2, EPCAM, CD70), including an ongoing CD3×MUC16 bispecific (ubamatamab) trial in RMC and SMARCB1-deficient epithelioid sarcoma (NCT06444880).