OnCo
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Caution: PD-1 rechallenge after progression on immunotherapy (RCC)

Restarting immunotherapy alongside a targeted pill after immunotherapy has already failed adds side effects and no benefit.

CONTACT-03 (atezolizumab + cabozantinib vs cabozantinib) and TiNivo-2 (nivolumab + tivozanib vs tivozanib) were both negative. After IO progression, single-agent TKI (cabozantinib, tivozanib, axitinib) or belzutifan is standard; IO rechallenge is reserved for trials.

Rationale
Acquired resistance to PD-1 blockade is not overcome by adding a VEGF-TKI; the apparent activity of IO-TKI after IO in single-arm studies reflected the TKI.
Evidence
Two negative phase 3 trials.

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