Ep 88: Negative Adjuvant Doublet Studies (CM915, KV010, RELA098)

Melanoma Matters: Why Adjuvant Doublet Immunotherapy Fell Short

Hobbies - James wishes he was surfing more

This episode breaks down three negative adjuvant melanoma trials testing combination immunotherapy against anti PD 1 monotherapy. The discussion focuses on why toxicity rises without clear efficacy gains, and what these results mean for adjuvant and neoadjuvant strategy going forward.

James Larkin and Sapna Patel also dig into a bigger question: if combination therapy helps in metastatic disease, why does it seem to lose its edge in microscopic or adjuvant disease?

Key topics

In this episode, the hosts review three adjuvant trials:

• CheckMate 915
• Relativity 098
• KeyVibe 010

• The bottom line across all three studies is negative efficacy for combination therapy versus monotherapy in the adjuvant setting.
• The conversation emphasizes toxicity and discontinuation as a major issue with combination arms, especially when patients stop early because of adverse effects rather than progression.
• They revisit the CheckMate 915 dosing question, noting that the ipilimumab exposure in that study was much lower than the classic EORTC adjuvant regimen.
• The hosts compare dosing intensity and cumulative dose across adjuvant and metastatic settings, including the idea that dose density may matter as much as total dose.

• The episode raises a larger strategic question for melanoma care:
  • Should adjuvant therapy remain monotherapy?
  • Should neoadjuvant treatment replace some adjuvant use?
  • Should patients receive both?