RE:Interesting Context from Jones ResearchThis context is not great for TH1902. They are nowhere near 30% ORR, in fact they are at 5.5% (2 PR out of 36 patients).
I still doubt docetaxel as cytotoxic agent. There is lot of patients resistants to it. Also, let's see if they will really enroll patients biopsy tested recently for high sortilin overexpression on their tumors. Good patient selection is critical in targeted therapies like PDCs.
Sorry to come back to Lutathera again, but this PDC was approved based on progression free survival (stable disease), and the ORR (CR +PR) was 13%. But they achieved that by only treating patients that were tested for somatostatin receptor overexpression by PET scans using Ga68-Dotatate. Thera will need to take the biopsy path wich is much more difficult.
Imagine what kind of results they would have had with Lutathera without testing patients for somatostatin receptor overexpression. They would not have been approved without it. It was an essential part of the whole treatment strategy.
So TH1902 is not dead, but the road ahead is long and will cost a lot of money. Their path to approval seems to be through a relatively long and large phase III to show a real benefit in stablizing the cancer with progression free survival (PFS) as the primary endpoint. It takes time to get complete PFS data because you need to wait for progression of the diseasein all patients to know the real extent of the efficacy, and here efficacy is stable disease.
SPCEO1 wrote: For reference, Trodelvy was approved with a 31% ORR (4%
CR; 27% PR) in TNBC and Elahere was approved with a 32% ORR (5% CR;
27% PR) in FR-alpha+ platinum resistant ovarian cancer. With respect to safety,
the construct appears better tolerated than both chemo and approved ADCs.
Specifically, grade 3 or greater TRAEs were reported at a rate of ≤12%, while
the Phase III ASCENT trial of Trodelvy saw grade ≥3 TRAEs of 11% for diarrhea
(<1% for chemo), 52% for neutropenia (33% for chemo), 8% for anemia (5% for
chemo), and 6% for febrile neutropenia (2% for chemo). In our call, management
highlighted the notable lack of both neutropenia and alopecia in patients treated
with sudocetaxel zendusortide as indicative of the improved safety profile of
the drug. Management also reiterated that the protocol amendment is expected
to focus the trial on one or two indications that sudocetaxel zendusortide is
most likely to succeed in. Given the data presented so far, we find it likely that
this will include ovarian cancer and/or TNBC. If this proves to be the case,
we anticipate adjusting our model to replace endometrial cancer with TNBC.
Notably, ~289,000 patients are diagnosed with TNBC vs ~66,000 patients with
endometrial cancer. If TNBC is, in fact, included in the amended trial, we expect
to provide a more detailed analysis of which of these patients we believe are
most likely to benefit from THTX's ADC.