Just a brief history on our previous mTNBC trials

Just a brief history on our previous mTNBC trials and how LL stacks up to its competitors on this indication:

https://www.reddit.com/r/CYDY/comments/pd2vrb...;context=3

My thoughts on the possibility of BTD for LL on mTNBC
Opinion
Jing_2021 posed this question to me and I answered it below:

FDA just told ROCHE to withdraw their application for accelerated approval of the therapeutic atezolizumab following a consultation regarding the FDA's assessment of the "current mTNBC treatment landscape."

https://www.joplinglobe.com/region/national_b...8f0d5.html

Regarding the current mTNBC treatment landscape, could you pls comment on this and what will be the implication to leronlimab's BTD application?



Thanks for your question Jing_2021



So I replied:

Well, the FDA asked ROCHE to withdraw because there was no benefit to adding Atezolizumab to Paclitaxel. By itself, Paclitaxel gives a progression free survival of 5-6 months. Adding Atezolizumab to Paclitaxel proved worthless. The PFS remained 5-6 months. (Bear in mind here, that Paclitaxel is a chemo agent used to treat PD-L1 Breast Cancer, not mTriple Negative Breast Cancer. Remember from the 7/19/21 Press Release, the Standard of Care PFS for mTNBC is only 2 months).

Comparing that outcome, (but it's not apples to apples since one is used to treat PD-L1 Breast Cancer and ours to treat mTNBC), to the most recent results of the Compassionate Use study of LL in Breast Cancer, the PFS arrived at here was about 13 months. 5-6 vs. 13 months.

In addition, the addition of Atezolizumab did not improve Overall Survivability. Paclitaxel gives an OS by itself of about 20 months. Adding Atezolizumab added another month or two.

In contrast, our Compassionate Use Study reveals an overall survivability of 34-59 months, or 3-5 years. This was determined by use of statistical analysis and extrapolating a death rate to determine time at which 50% of original 30 patients would likely be dead by, and that came out to time range.

The FDA recommended withdrawal due to the current landscape of medications for treating mTNBC. Certainly, the FDA is aware of this most recent LL study and how it utterly blows the doors off the outcome from Atezolizumab with Paclitaxel. We just may have been the reason why the FDA made this recommendation.

With regard to BTD, break through therapy designation, I believe Leronlimab is the best drug for mTNBC out there right now. No one can touch our PFS or OS. We double the stand alone Standard of Care Paclitaxel for PD-L1 BC in PFS and OS. We have no side effects stand alone, but in this Compassionate Use Study of Leronlimab in Breast Cancer, LL was combined according to each Treating Physician's Choice with any one single-agent chemotherapy drug administrated according to local practice: eribulin, gemcitabine, capecitabine, paclitaxel, nab-paclitaxel, vinorelbine, ixabepilone, or carboplatin. Side effects of chemotherapy produce considerable morbidity.

Now, I don't know the quality of life these patients live once they go from the beginning of PFS to the end of their lives. Since chemotherapy is used with Leronlimab, the side effect of the overall treatment remain. Leronlimab does not prevent any of the side effects induced by the adjuvant chemotherapy regimen. However, using Leronlimab extends Progression Free Survival from the current 6 months to about 13 months. Leronlimab increases current Overall Survivability from 20 months to 34 - 59 months or 3-5 years. What's the quality of these say 4 years? I'd say much better than the 20 months which results following use of Paclitaxel alone, otherwise, why would the patient live twice as long, in a more virulent type of Breast Cancer: mTNBC? With the use of Leronlimab, effectively, you are doubling their life expectancy, and the quality of that life would have to be better, otherwise, it would not go one for twice as long.

Going back to the Press Release on 7/19/21, we saw that only 4 injections of Leronlimab, (along with Carboplatin x4 weeks, chemo) saved the lives ~21 out of ~29 mTNBC patients and gave a Progression Free Survival of about 6 months. (equal to the use of Paclitaxel, but in a less virulent type of Breast Cancer: PD-L1.)

In that 7/19/21 Press Release, the relevant biomarkers indicated that the return of the cancer occurred at about the 6 month point, (but by continuing Leronlimab at a lesser dose, 350mg along with chemo of choice, this increased to 8 - 13 months in the Compassionate Trial) and was verified as such to be there by measuring the quantity of CAMLs (cancer associated macrophage cells) and CTCs (circulating tumor cells). I propose we can also implement the measuring of the tumor markers in conjunction with indefinite weekly administration of Leronlimab with chemo treatment of choice.

Making an educated guess, in the 7/19/21 Press Release, the cancer probably started to regrow to produce the CAMLs at about the 4-5 month point and in the Compassionate Trial at about the 9-11 month point, (that is, without any treatment at all, neither Leronlimab nor chemo of choice). The cancer spontaneously returns without repeat treatment.

Instead of using Diagnostic Imaging which was used in the Compassionate Use Trial of LL in BC, (In this study, patients will be evaluated for tumor response approximately every 3 months or according to institution's standard practice by CT, PET/CT or MRI with contrast (per treating investigator's discretion) using the same method as at baseline. Tumor measurements will be done using RECIST v1.1), another solution would be what was done in the Press Release of 7/19/21 which was to measure the CAMLs and CTCs to determine the return of the cancer. From what we have seen, this test may safely be given every 4 months or so following LL & chemo administration to determine if they reside above a certain threshold which would indicate return of cancer, and to base the re-administration of the 4 injection series of 700mg Leronlimab injections along with chemo or the indefinitely scheduled 350mg Leronlimab injections along with chemo based on the tumor markers.

My gut here, is if this Compassionate Use of LL in BC Trial were conducted using 700mg instead of 350mg, our results would have been even more amazing and our PFS would have exceeded 18 months and OS > 7 years. Certainly, this trial confirmed that giving Leronlimab and chemo of choice on a weekly basis, and indefinitely, (not just for 4 weeks and stopping), was superior to just giving it as a series of 4 weekly injections with chemo and then just stopping and seeing what happened. In the Compassionate Use of LL in BC Trial, this indefinite weekly scheduled dosing of Leronlimab with chemo finally came to an end when the measured Tumor using imaging became negligible.

This indefinite scheduled dosing of Leronlimab with chemo, once weekly until Tumor measurements using RECIST produced exceedingly superior results than the series of 4 weekly LL injections with Carboplatin even if only 350mg Leronlimab was used. PFS went from 6 months to 13 months. OS was greater than a year, (but was really not calculated as all who responded lived to at least the year point), but definitively went to 3 - 5 years with the indefinite and scheduled manner. With Paclitaxel alone, PFS is about 5.5 months and OS is about 20 months. (Again, remember here, that Paclitaxel is a chemo agent used to treat PD-L1 Breast Cancer, not mTriple Negative Breast Cancer. Remember from the 7/19/21 Press Release, the Standard of Care PFS for mTNBC is only 2 months). To gain Breakthrough Treatment Designation, we need to obliterate Paclitaxel, (even though it is an apples to oranges comparison), with as little chemo as possible.

Let's see where Dr. Recknor takes this.

I'd still say BTD remains very promising.