Melanoma Matters

Melanoma Matters: Why Adjuvant Doublet Immunotherapy Fell ShortHobbies - 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 topicsIn this episode, the hosts review three adjuvant trials:CheckMate 915Relativity 098KeyVibe 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?

James asks the big question

In this episode, Sapna and James discuss the INTerpath-001 press release describing primary endpoint (RFS) and key secondary endpoint (DMFS) findings from the randomized phase 3 study of individualized neoantigen therapy plus pembrolizumab for resected stage IIB to IV melanoma. No data were shared, only descriptive findings of "statistically signficant" and "clinically meaningful" results. As James puts it, one of these is binary, the other is subjective.

In this episode, James and Sapna debate how to pronounce the newest FDA approved treatment for melanoma: T-U-D-R-I-Q-E-VThey discuss the FDA Cell and Gene Therapy Advisory Committee's review of the single-arm IGNYTE data and key issues around if this represents a local or systemic therapy, the maths around calculating response rate, and importantly how to identify optimal tumor characteristics for this treatment - what Sapna calls "Larkin-izing" the data.It's a long episode with a short fact check and lots of shoutouts to Kevin Harrington for his work in this space.

In this episode, Sapna and James talk tv shows - The Gambler and His Cowboys, Brassic... They discuss the paper from NKI on surgical considerations for TIL harvest published in BJS in 2025. Topics of interest include optimal anatomic site(s), size (is bigger always better?), number of lesions and which of these components comprise a successful ex vivo expansion of TIL