Neoadjuvant treatment of Melanoma

Session Monday 4pm


Re-cap
neo-adjuvant: treat with drugs first to shrink the tumour, then operate
adjuvant: operate, then treat with drugs

Rationale (reasons) for neo-adjuvant approach
- information about biology- how aggressive is the disease? Prognostic information
- gives information about how well therapy works
- downgrading/ downstaging surgery


A neo-adjuvant Dab/ Tram trial was stopped for efficacy
Lancet Oncology 2018- stopped for efficacy

T-Vec neoadjuvant for IIIB- IVM1a
pathological response 21%

Ipi vs Nivo neo-adjuvant
8% Grade 3/4 toxicity
has promise, impressive response but risk of progression - so needs close follow-up



Combination treatment of advanced Melanoma- IDOs or SD101 plus Pembro
Alex Menzie

Challenge remains: not all patients respond to PD1 or continue to respond to PD1 inhibition, so more treatment options are needed

Wolchok NEJM 2017- 39% OS at 3 yrs on Ipi+ Nivo


IDO plus PD1

Ph2 looked great for Epa plus Pembro

Another IDO-
Indoximod plus Pembro





Illuminate 301- Phase 3 study

A Study of IMO-2125 in Combination With Ipilimumab Versus Ipilimumab Alone in Subjects With Anti-PD-1 Refractory Melanoma (ILLUMINATE-301) (ILLUMINATE-301) https://clinicaltrials.gov/ct2/show/NCT03445533

IMO-2125 is a so-called TLR agonist (TLR = toll- like receptor, IMO-2125 blocks TLR9, agonist = it enhances the function of TLR9). TLR9 sits on the surface of dendritic cells and B-cells and once they are activated, these cells will activate T-cells.
In this trial, patients who progressed on PD1s will receive either Ipi 4 doses intravenously or Ipi iv plus IMO injected into the tumour.

IMO-2125 is produced by Idera and has received FDA fast-track designation for the combination with Ipi- so definitely something to keep an eye on.







5 year survival Pembro on Keynote 001

34% alive after 5 years
41% of treatment-naive patients were alive after 5 years


Biomarker to predict survival and durability of response in Melanoma

PFS after 1 year tm by CT vs PET

PET better than CT to predict durability of SD