It’s now been almost four full 28 day treatment cycles with investigational PI3K inhibitor IPI-145 and it’s time for another CT scan (#4) tomorrow. This will be my third since August and they’ll be measuring my spleen, liver and many lymph nodes for shrinkage or reduction in lymphadenopathy as a result of the therapy. The key words I’ll be listening for from Dr Flinn afterwards will be Partial Remission or simply PR. 50% reduction across the board should be attainable from the numbers I’ve been watching and it would be an awesome Christmas gift!
Bringing a new drug to market is very expensive. There is a lot at stake and investors follow the process closely. For the record, Monday morning biotech stock market quarterbacks or financial analysts are driving my nuts. When I try to research drug development news and updates, there is probably 10 articles by these market analysts for every 1 clinical or scientific one. It’s like search engine SPAM. This one came to my inbox this morning and is almost depressing. ASH 2013 just wrapped up a week ago. There are no good , effective FDA approved treatments for my particular chromosomal mutation. For me, this drug IPI-145 seems to be working miracles in managing my disease but to the analysts, it’s too little too late in a market that seems to be getting crowded in recent months.
Why Investors Are Writing Off Infinity PharmaBY David Sobek | 12/18/13 – 08:00 AM EST
Way to ruin a good thing. Fooey on you guys!
After 3 1/2 28 day cycles of treatment in this ipi-145 clinical trial, The trends from my CT scans and CBC tests are all pointing towards more normal blood counts and hopefully a partial remission. The WBC and Neutrophil counts show quite a bit of variability from week to week but they are trending in more normal directions. Can’t thank Dr Flinn and the team at Tennessee Oncology/Sarah Cannon Research enough.
Merry Christmas to Don!!!
This Just In: Apparently I’m in a high risk, bad-acting group of patients :-O
You can read the related article on OncLive. Disclosure: Dr Ian Flynn is my Oncologist/Hematologist and IPI-145 is the trial drug I take to manage my CLL.
Feels like I’m part of an elite club.
IPI-145 Data in Patients with CLL The presentation, “Preliminary safety and efficacy of IPI-145, a potent inhibitor of phosphoinositide-3-kinase-δ,γ, in patients with chronic lymphocytic leukemia” (Abstract #677), included 67 patients evaluable for safety and 47 evaluable for clinical activity. Among the 67 patients enrolled in the study, 52 had advanced disease and had progressed during or were refractory to, intolerant of, or ineligible for established therapy. An additional 15 treatment-naïve patients were enrolled who were age 65 or over or high-risk, defined as having 17p deletions or p53 mutations.Clinical ActivityUpdated data from the ongoing Phase 1 study showed that IPI-145 is clinically active in patients with relapsed/refractory CLL. Treatment with IPI-145 at doses ≤ 25 mg BID in patients with relapsed/refractory CLL led to a nodal response rate of 89 percent and an overall response rate of 48 percent as defined by the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria1, including one complete response and 12 partial responses among 27 patients evaluable for response. The median time to response was less than two months. Seventy-five percent of patients (six of eight) treated for 12 months or longer remain progression-free on treatment.Among 12 patients evaluable with 17p deletions or p53 mutations who received IPI-145 at doses ≤ 25 mg BID, there were six partial responses, five patients with stable disease, and one disease progression due to Richter transformation. Patients with CLL with 17p deletions or p53 mutations generally have a poor response to chemotherapy and worse prognosis.2 Preliminary data in treatment-naïve patients showed a reduction in adenopathy in all six patients. Three of these six patients had nodal responses, including nodal responses in two patients with p53 mutations.
The ASH 2013 (American Society of Hematology) annual meeting kicks off in New Orleans today. There will be many presentations; this one I am most eagerly awaiting. It presents current data on the Infinity Pharmaceuticals ipi-145 clinical trial I am enrolled in. The presenter, Dr Ian Flinn is my Hematologist/Oncologist. You can read the full abstract here. Here’s a tidbit.
#677 Preliminary Safety and Efficacy Of IPI-145, a Potent Inhibitor Of Phosphoinositide-3-Kinase-δ,γ, In Patients With Chronic Lymphocytic LeukemiaProgram: Oral and Poster Abstracts
Session: 642. CLL: Therapy, excluding Transplantation: Clinical Trials of B Cell Receptor Signaling InhibitorsMonday, December 9, 2013: 5:30 PM295-296 (Ernest N. Morial Convention Center)
Ian Flinn, MD, PhD1, Manish Patel, MD1,2*, Brad S. Kahl, MD3, Steven M. Horwitz, MD4, Francine M. Foss, MD5, Yasuhiro Oki, MD6, Pierluigi Porcu, MD7, Jennifer Sweeney, BS8*, Kerstin Allen, MA8*, Kerrie Faia, MS8*, Patricia Harris, MPH8*, Joi Dunbar, PharmD8*, Howard M. Stern, M.D., Ph.D.8*, Patrick Kelly, MD8 and Susan O’Brien, MD6
Clinical activity has been observed in R/R CLL pts at all doses of IPI-145 studied from 8 mg to 75 mg BID and in pts with R/R high-risk disease (TP53 mut/17pdel). Treatment-related lymphocytosis is rapid, with the median ALC return to baseline within 6 cycles of treatment. Reduction in adenopathy occurs early with no apparent dose-dependence. Nodal responses (>50% reduction in adenopathy by CT assessment) occurred in 79% of pts after 2 treatment cycles. Best overall response (based on investigator assessment per IWCLL) in evaluable pts to date (median [range] number of cycles 5.1 [1-21.1]) is 52%, with 1 CR, 15 PR, 14 SD and 1 PD. The ORR for the 19 evaluable pts treated at ≤25 mg BID is 53% (10/19; including 1 CR) and 7 of the 8 SD pts achieving nodal response. Resolution of lymphocytosis may lead to an increase in best ORR for SD pts who remain on study. R/R pts with high-risk disease (TP53 mut/17pdel) had similar ORR.
Conclusions: IPI-145, an oral, potent PI3K-δ,γ inhibitor, appears well tolerated and has shown promising clinical activity in pts with R/R CLL across the range of doses examined. The PK/PD and clinical activity suggest that 25 mg BID is a biologically active dose in R/R CLL, and this dose has been selected for an upcoming randomized Phase 3 trial in R/R CLL. Updated data from treatment-naïve CLL pts who received IPI-145 at 25 mg BID and R/R CLL pts who received IPI-145 at 25 mg and 75 mg BID will be presented.
I’ve charted some of the metrics from a few months of weekly CBC tests. Treatment in the clinical trial began the first week of September and outcome so far is both expected and good. Most of my blood counts have returned to where they were about 3-6 months before I started any treatment. The neutrophil counts have been the most stubborn and variable but they do seem to be rebounding now. The ipi-145 clinical trial (now in cycle 4) will continue open-ended for me so the values should hopefully continue to normalize.
I’ve now completed 3 28 day treatment cycles in the Phase 1 clinical trial for IPI-145. Most of my blood counts with the frequent exception of the neutrophils have been rebounding steadily. Most are back to where they were in May 2013, 3 months before I began treatment. The initial goal was to drop-kick this CLL. So far, we seem to be doing just that.
Here’s a snippet from his post about the upcoming ASH (American Society of Hematology) conference in New Orleans, LA in December. My own doc, Dr Ian Flinn will be presenting on trial data with ipi-145. I can’t wait. There is a video on page one but the audio did not play well for me. Here’s page three from the article
Bumper Crop of New Agents
The rest of the studies focus on the new agents. We have several ibrutinib trials, including a single-agent study in patients with or without 17p deletion. There will be the final analysis of bendamustine and rituximab plus ibrutinib. Do you need the chemotherapy? Do you need the bendamustine? There will be another abstract with rituximab and ibrutinib alone.
This isn’t the only exciting drug. There are phosphoinositide (PI) 3-kinase inhibitors, which appear to be very good and are very impressive, perhaps as good as ibrutinib when you combine them with a drug like rituximab. In fact, a recent study of rituximab-idelalisib vs rituximab-placebo was closed early because of a survival advantage.
We are also going to be seeing a list of new PI 3-kinase inhibitors for the treatment of CLL: a new delta inhibitor, a new gamma inhibitor, and others. We’ll have to see which of these provides an advantage over the others, if at all. But in any event, we have great new drugs that will be changing the landscape of non-Hodgkin lymphomas, Hodgkin lymphoma, and chronic lymphocytic leukemia.
This is Bruce Cheson, signing off for Medscape Hematology. I will be back with you after the ASH meeting in New Orleans. See you there. Goodbye.