ideasIdea
Biomarker-selected adjuvant therapy in RCC (ctDNA, CAIX PET, gene signatures)
Adjuvant immunotherapy helps a few patients and exposes many to harm. Tests that find the few would make the trade-off far better.
KEYNOTE-564 and LITESPARK-022 treat everyone at high pathological risk; most would never relapse. RCC sheds little ctDNA, so alternatives include CAIX PET for residual disease, kidney-specific ctDNA/methylation assays, and transcriptomic signatures (ClearCode34, angiogenesis/T-effector scores).
Hypothesis
A post-nephrectomy residual-disease or high-risk signature can identify a subgroup with ≥30% two-year relapse risk in whom adjuvant pembrolizumab ± belzutifan gives an absolute DFS gain of ≥15%, while sparing low-signature patients.
Rationale
Number needed to treat in KEYNOTE-564 is high; toxicity of a year of IO plus HIF-2α inhibition is not trivial; precedent in IMvigor011 for ctDNA-guided adjuvant IO in bladder cancer.
What would test it
Biomarker-stratified adjuvant trial with a surveillance arm for low-risk-signature patients; CAIX PET substudy.
Maturity
early clinical