Melanoma is one of the basket cancers in 1b they are now in trial for. We saw preclinical that advanced melanoma highly overexpressed sortilin1 so it was a very good target for this trial. Melanoma has very few options for advanced, metastatic cancers and it is also a very large and growing market, so it is one that if TH1902 can show some effectiveness in, it would be a huge market opportunity. So what is the current state of play there?
Here is a new drug in a Phase 3 looking to get a BLA later in the year and what an analyst thinks would be "clinically meaningful" as far as results. The company is Iovance and the drug is what's called a TIL (tumor-infilitrating lymphocyte) and the drug name is Lifileucel. So the approach is not an ADC or PDC and completely differnent, but here is what the recent results showed and what the analyst thought were the hurdles for ORR and PFS to be "clinically meaningful" and find a market for the drug. They are reporting a second cohort of data; hence the discussion around cohort 2 & 4. The main points for use are the overall stats and how quickly they're moving to BLA.
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Lower ORR (29%) and duration of response (10.4 months) in Cohort 4 vs. Cohort 2 attributed to: 1) higher disease burden in Cohort 4 (higher LDH and more tumor lesions) and 2) longer prior use of anti-PD-1 therapy (~10 months in Cohort 4 vs. ~5 months in Cohort 2) – both of which are potential predictive factors for lower responses to TIL based on prior data presented by IOVA.
· Longer use of prior checkpoint inhibitors in Cohort 4 potentially reflects evolving standard of care; earlier use of checkpoint inhibitors in the adjuvant setting – which we believe may impact the ability to harvest “high quality TILs” from patients.
· Duration of response of 10.4 months remains clinically meaningful vs. standard of care chemo ~3-4 months, and continues to support approval – and potentially accelerated approval which remains a possibility.
· Iovance potency assay had no impact on response rates.
· Full data is expected to be disclosed at a medical meeting in 2H22.
· BLA filing remains on track for August 2022.
CONCLUSIONS: If TH1902 shows an ORR >30% and PFS > 10 months that would be considered pretty good for advanced melanoma. Current PFS is quite low for these patients for current SOC -- only 3-4 months, so definitely a fairly low bar to improve upon.
Also, notice they present the headline data and key stats and say full data to be reported at medical meeting in 2H, so THTX should be able to do that with the 1a data and the 1b data. Seems pretty straightforward. Lastly, this seems to indicate not just commerciality, but that it may be good enough for accellerated and seems to go pretty quickly to the BLA stage. Overall, I think their further testing around melanoma and seeing the high sortilin1 expression opened up a potentially very attractive market if they should see decent efficacy there. It would be as large as TMBC I think.