Before a CNS reg trial, several things need to be determined and agreed upon.
1. ~200K BrCa cases per yr in US with ~20% HER2+, ~50% of these develop CNS mets; therefore, does a pool of potential 20K pts represent a rare condition?
2. CNS mets is unmet medical need; therefore, what is the the SOC arm?
3. What is/are the appropriate primary endpoint(s) in CNS indication considering that this is an unmet medical need situation? ORR? PFS? Prior FDA action suggests a surrogate of survival would be appropriate.
4. Does ONT-380's (and active metabolite) ability to penetrate the CNS represent a "breakthrough" in terms of treatment of HER2+ CNS mets?
5. SPA on #2 and 3. Does, can or will #1 and #4 need to happen before #2 and #3?
Based on what has leaked already, discussions have been going on with FDA. On what exactly, still not known.
Definitely in CNS. Reasons why?
1. Strong tumor responses in CNS
2. Tumor responses in CNS and SD correlate with PFS
3. Unmet medical need in CNS for HER2+ mets
Pts enrolled in TDM1/ONT-380 combo
- T does not cross BBB according to literature data
- TDM1 is even larger MW entity than T; therefore, it is also unlikely to cross BBB
- Literature data shows that for pts on TDM1, CNS is location of 1st relapse. Data supports that TDM1 unlikely to cross BBB.
- Previous PIII Th3resa trial on TDM1 enrolled only pts that failed priorHerceptin (T) and Lapatinib (L) but without any CNS mets pts: mPFS was 6.2 months
- Currently no available, approved systemic therapy for HER2+ CNS mets - unmet medical need
Data in abstract
- Pt population: 100% progressed on T+taxane, 60% with CNS mets+, 44% failed prior Perjeta, 22% failed prior lapatinib
- mPFS overall pts: 6.5 months
- mPFS with CNS mets +: 6.5 months - view this as positive since these pts are much more advanced than Th3resa trial population
- mPFS in pts with PROGRESSIVE or untreated CNS mets: 6.7 months - view this as very positive
- mPFS in pts without CNS mets: 8.2 months - view this as very positive in light of Th3resa data. Data suggests that adding ONT-380 could extend mPFS.
- CNS data: 4 pts with ORR (2 CR, 2 PR): note that one PR from December data became CR - view this as very positive
- CNS data: CBR is 7/9 or ~78% (Pts with CR, PR or SD for 6 months) - view this as positive as the mPFS in CNS would appear to be 6 months as well.
Clearly CNS activity present with ONT-380. TDM1 highly unlikely to cross the BBB.
Release of Abstract Titles (Accessible via ASCO's iPlanner website)
MAY 16 AT 12:00 PM (EDT)
Abstract Slide Upload Deadline for all Oral, Clinicial Science, and Poster Discussion Session Presenters
MAY 18 AT 5:00 PM (EDT)
Abstracts Released on ASCO's Meeting Library
17:34 $ 1.04 Low 898
16:19 $ 1.287 76,372
16:19 $ 1.287 406
16:12 $ 1.29 High 6,635
16:12 $ 1.25 1,400
16:12 $ 1.2501 1,400
16:11 $ 1.26 100
16:11 $ 1.26 500
16:11 $ 1.26 500
16:11 $ 1.2601 500
16:11 $ 1.2601 500
16:00 $ 1.29 8,988
16:00 $ 1.28 500
16:00 $ 1.29 948
Go re-read the PR.
"If Oncothyreon is acquired within three years of the effective date of the current agreement, Array will be eligible for up to $280 million in commercial milestone payments."
Any payments would come from commercialization of ONT-380. In other words, the acquirer would pay Array after the drug is approved and the payments would be as milestones, likely sales based payments.
The $280M does not come in the form of payment upfront upon buyout.
Good points. Preclinical data also shows that not only does ONT-380 enter the CNS, but the active metabolite which is equipotent to '380 preferentially enters and localizes to the CNS.
Forgot to add, SABCS 2015 data is better than ASCO 2015 and that is the base case (ie. worst case). There is a significant number of pts still on study that are/were very close to surpassing key time on study to further improve on the SABCS 2015 data. In other words, it is very likely the data will further improve at the next update. Been told that updated Phase Ib data to be at ASCO 2016.
Yes it was a brutal #$%$.
No question that SABCS 2015 data was better than ASCO 2015.
Triplet combination is essentially a "supplemental" study in 3rd line.
CNS data is the key. No question that CNS data is phenomenal. Stable and decreasing size of tumor/lesions in the brain. CNS is a tough nut to get into thus ONT-380 effects in the brain are significant.
7/8 in newly diagnosed, untreated pts showed stable or decreasing size of lesions
12/15 in previously treated, progressive pts showed stable or decreasing size of lesions.
This TDM-1/ONT-380 combination for CNS pathway has a very good chance at being a registration trial.
Likely interim until the new CEO comes on board. Typical during transition since Henney is only interim CEO.