6 Comments

I hope this is true! I'm on immunotherapy now to prevent cancer recurrence. Pembrolizumab (brand name Keytruda).

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Hi Mark, I'm sorry to hear about that you've been battling cancer! Glad you're cancer-free at the time at least! Pembro is certainly an effective and popular immunotherapy! There has been some recent interesting work that has examined the necessary length of maintenance treatment that found that shorter windows (~2y) show the same durable remission as longer ones.

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I alas failed Keytruda for squamous cell carcinoma of the head and neck, in 2023; right now I'm on an antibody-drug conjugate from Seagen called PDL1V, which, as the name implies, also targets PD-L1: https://jakeseliger.com/2024/05/20/in-which-the-antibody-drug-conjugate-adc-pdl1v-shrinks-the-tumors-in-my-neck-and-buys-me-more-time/. May CT scans showed that it had shrunk tumors; scans from last week, though, appear to show tumors adapting to it as well.

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Yes, ICI use in HNSCC hasn't been as successful as hoped. I'm a big fan of the ADC approach and ICI-type ADCs are cool - ideally the best of the chemo and immuno approaches combined. Glad you had a response to the Seagen ADC even with the signs of adaptation! Lots to learn about optimal payloads and mechanism of action for ADC. We need more like T-DxD.

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Another ADC, this one by Abbvie: https://clinicaltrials.gov/study/NCT06084481?term=ABBV-400&rank=1 is a possible next step. But its payload is also MMAE, and if my HNSCC has somehow managed to adapt to MMAE already, then something else probably makes more sense.

Another possibility is from TScan Therapeutics, in the form of "A Basket Study of Customized Autologous TCR-T Cell Therapies." https://www.clinicaltrials.gov/study/NCT05973487?term=tscan002&rank=1 Promising, but also first-in-human happened a few months ago, if I recall correctly, and a lot of promising approaches don't actually work.

A big part of the challenge is also mechanical-logistical: https://bessstillman.substack.com/p/please-be-dying-but-not-too-quickly. Since none of these trials are using a distributed-site process, I have to be able to commute or move to the site itself, which is, to understate things, not so easy right now.

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I agree. We need trial decentralization. There was a push during COVID but sponsors don't like relinquishing control because of the stakes.

We also need real-time trial updates and a better system for maximizing trial utilization. The numbers i'm familiar with is that only 5% of trial-eligible patients end up enrolled. Some of it is too strict enrollment criteria.

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