RE:RE:RE:RE:Over $400k annually for…Here's the earliest data releases on TIVDAK. They called their trial a Phase1/2 throughout and coming out of the Phase 1 they did a basket but most of the efficacy was seen in cervical and since it was unmet, that's probably where the FDA and CMO guided them for the Phase 2. Although, I think the Phase 2 did enroll for a few other types, like the Phase 1b extension, but they just focused in on cervical given the unmet need.
Phase 1 - they did the dose-escalating (3+3 design) part with 27 patients in ovarian, cervical, endometrial, prostate, bladder, oesophageal, NSCLC, SCCHN (the last squamous head neck was a disaster as the tumor haemorrhages and patient died). Then the Part b expansion on multiple cancers types for safety and efficacy. It enrolled Cervical (34 patients), Ovarian (36), Prostate (18), Oesophageal (15), Endometrial (14) and NSCLung (15) for total of 147. They focused on cervical from there.
Patients Cervical Phase 1b: n=34, 7 finished Part b and 27 didn't (5 for safety, 16 for progression, 6 other).
SO --only 7 patients carried on fully through Part b expansion. I suppose that's a problem with any of these hard to treat cancers and especially the 3L and 4L ones like THTX is doing.
Safety: Grade 2 TAEs in 16 patients. No grade 4-5 events. Lots of conjunctival toxicity (eyes) 75% of patients. Figured out a mitigation strategy for that and went down to 32%.
Efficacy from Phase 1b extension on 34 patients:: Obj Response 32% all partial (PR). Durable benefit for 50% (at least 12 weeks). Median duration of 8.3mo and median progression free survival of 6.4mo. All their responses were in patients with no/1/2 prior lines and the 7 who had >3 prior lines had no responses.
Target Lesion shrinkage: 7 of the 34 saw increases, 14 less than 30% shrinkage (so not a response according to RECIST) and 11 shrank 30-90%. One was at that 90%, all others at the 30-60% level.
With this data they concluded it was "substantial efficacy" and "manageable safety". But they did want to try a different dosing schedule for the cervical patients and that likely led to the long time frame between P1 and P2.
The hurdle to overcome in cervical for second line are ORRs generally between 9-15%. Irinotecan is 21% (I think that's the chemical now shown in the THTX presentation). That's why the 32% ORR number stood out. Supposedly there is no standard of care yet for cervical second line.
Looking at this, I can see why they keep saying they will consult with FDA on Phase 1b. The probability of death or disease progression is just very high --weak patients, drug resistant, close to death already and lots of co-morbidities kicking in. So maybe that's where you optimize numbers and types to hit high unmet needs and get enough patients so you have the time and data to see real efficacy. They did close to 150 patients in their extension trial with two cohorts at 30+ patients. Whatever it is, the consultation likely will focus the resources around where they see an unmet need intersecting with decent efficacy. If they all look that way then maybe you get higher patient numbers in the largest types and highest unmet need. I don't know, but it will be interesting to see. It wouldnt' surprise me that given the fast track, they will be sharing thoughts with FDA in the fall/winter so that they can hit the ground running with the extension and then that should really tell them where Phase 2 should go.
Hope this helps.
qwerty22 wrote: Just to follow up on that. Some of the indications thtx has picked for part 2 (I'm thinking r/r pancreatic cancer) have a very short list of approved drugs and some of those drugs have very horrible looking profiles from an efficacy perspective (my memory is there is one drug with a 10-15% ORR in pancreatic cancer that got approval). If they see activity in pancreatic cancer for example you might be looking at a short path to approval.
qwerty22 wrote:
Another variable to consider is the treatment landscape for metastatic cervical cancer. The limited drugs approved may have lowered the bar on this one. It definitely looks like a mixed bag of results. It would be interesting to see the very earliest data releases on this program to see whether you could discern an approvable dataset at that time.
Another interesting number coming out of this trial is
"The median time to response was 1.4 months (range, 1.1-5.1), with activity generally observed within the first two treatment cycles."
Not so much for approval but for our wait for efficacy data now. This ADC shows a very fast measurable response at the start of treatment hopefully th1902 obliges in this way and helps with the wait time for an efficacy announcement.
Wino115 wrote:
Another ADC is good news, especially as the BLA was filed in Feb, Accellerated App granted in April, and now approved in Sep. All on phase 2 with 101 patients and an objective response of only 24% and durability of response of 8 months in cervical cancer, but with a high percentage of safety issues many of which are on the serious side (50% for hemoglobin and lymphocyte decrease and 40% peripheral neuropathy) .
So the ADC not internalizing a lot of the chemo clearly leads to issues with dosage, duration and treatment window. More numbers and a timeline to keep in mind. On that timeline, you could see TH1902 move pretty fast based on positive results.