Thursday, May 23, 2013

ASCO 2013: Press Release and Abstract about Idelalisib (CAL-101 or GS1101) in Treatment Naive CLL Patients

This is why I go to ASCO and ASH and hope to get to Europe for IWCLL. To get the inside scoop on these studies. To talk to the investigators about the data between the lines in their abstracts.

And to hear the good news.

I can't wait to push the presenters to get more of the details, but the overview in the press release is certainly impressive. 

All nine patients with 17p del or mutated P53 responded and three had a CR (complete response).

93% progression-free survival at two years. And I love the fast disappearing B symptoms.  Us patients just seem to feel so much better very quickly on most of these new small molecules.

Now admittedly this is an easy group to treat, all treatment-naive so the number should be good.

The 17% with significant pneumonia is more worrisome to me than the 1 in 4 with elevated liver enzymes. That usually resolves with stopping meds, and one can usually restart at a lower level without recurrent liver issues, but pneumonia can be fatal in CLL.

What I want is more information on those not still on the trial?

Why did the 17 of 64 drop out? What was the cause of the death in the three brave patients?

Why does the abstract say 18 drop outs and four deaths?  I have pasted it at the end

Why are the CR levels so low with this and with ibrutinib? FCR has better numbers, admittedly at a much higher cost.

Does  it really matter that a low level of disease is hanging around? Maybe not? Only time will tell.

Still I am glad to see such strong results with another very active tyrosine kinase inhibitor.

The more potent yet gentle treatment options the better.

The future is looking brighter and brighter for those of us with CLL.

Remember this is a press release from the maker of the drug, so please take a critical look at  what Gilead had to say about their promising new agent and send me your comments on what you like and what  gives you pause:

Gilead Announces Response Data from Phase 2 Study of Idelalisib for Previously Untreated Chronic Lymphocytic Leukemia

-- Regimen Achieves 97 Percent Overall Response Rate with Estimated Progression-Free Survival at 24 Months of 93 Percent --
-- Results from Study 101-08 and Other Idelalisib Clinical Studies to Be Presented at American Society of Clinical Oncology Annual Meeting --

FOSTER CITY, Calif.--(BUSINESS WIRE)--May. 15, 2013-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced results from a Phase 2 study (Study 101-08) evaluating idelalisib (formerly GS-1101), an investigational, targeted, oral inhibitor of PI3K delta, in combination with rituximab for older patients with treatment-naïve chronic lymphocytic leukemia (CLL). This regimen achieved a complete response (CR) rate of 19 percent and an overall response rate (ORR) of 97 percent, with estimated progression-free survival (PFS) at 24 months of 93 percent. Detailed results will be presented during an oral session at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago (Abstract #7005).

CLL is a slow-growing cancer that induces the production of too many mature white blood cells. It is the second most common type of leukemia in the United States and can lead to life-threatening complications, including serious infection. Currently, patients with CLL are usually treated first with rituximab in combination with one or more chemotherapy agents.

“New therapies that can drive CLL into remission while potentially avoiding or delaying the need for chemotherapy would represent a much needed clinical advance,” said Susan M. O’Brien, MD, Ashbel Smith Professor of Medicine in the Department of Leukemia at the University of Texas MD Anderson Cancer Center in Houston and a principal investigator of the study. “The high overall response rate and durable disease control observed in this Phase 2 study suggest that idelalisib in combination with rituximab could become an important therapeutic option for CLL patients new to treatment.”

Among the 64 patients in the study, Kaplan-Meier estimated PFS at 24 months was 93 percent. The median time on treatment was 14 months, with 33 patients remaining on treatment. The median time to response was two months. No relapses on study have been reported. The nine patients with chromosome 17p deletion (del 17p) (n=6) or mutation in the TP53 gene (n=3), which have been linked to poor prognosis, all responded to therapy including three with a complete response. Ninety-four percent of patients with thrombocytopenia at baseline responded to treatment (16/17), as did all patients with anemia at baseline (17/17). Of patients with systemic symptoms such as extreme fatigue, fever, night sweats or weight loss (known as “B symptoms”) at baseline, 77 percent (20/26) were asymptomatic by eight weeks.

Patients completing 48 weeks of therapy without progression could continue to receive idelalisib in an extension study. Forty-three patients completed 48 weeks of treatment (21 discontinued – 17 due to adverse events, three due to death and one due to other reasons); 40 patients entered the extension study and 33 remain on treatment.

During the primary and extension study, Grade 3 diarrhea and/or colitis was reported in 33 percent of patients, Grade ≥3 pneumonia in 17 percent and Grade ≥3 transaminase elevations (measure of liver function) in 23 percent of patients.

“These results demonstrate for the first time idelalisib’s potential benefit for patients with a previously untreated hematological malignancy,” said Roy D. Baynes, MD, PhD, Senior Vice President of Oncology and Inflammation Therapeutics at Gilead Sciences. “Based on these promising data, we are now evaluating Phase 3 study designs for idelalisib as part of a frontline treatment regimen for CLL patients.”

Idelalisib’s clinical and safety profile for a number of blood cancers will be characterized in six additional oral or poster presentations at ASCO 2013:

Chronic Lymphocytic Leukemia (CLL)
Final results of a Phase 1 study of idelalisib in patients with relapsed or refractory CLL (Abstract #7003; oral session).
Update on a Phase 1 study of idelalisib in combination with rituximab and/or bendamustine in patients with relapsed or refractory CLL (Abstract #7017; poster session).


Indolent Non-Hodgkin’s Lymphoma (iNHL)
Combinations of the PI3K delta inhibitor idelalisib with rituximab and/or bendamustine are tolerable and highly active in patients with previously treated, indolent non-Hodgkin lymphoma: Updated results from a Phase 1 study (Abstract #8500; oral session).
Final results of a Phase 1 study of idelalisib, a selective inhibitor of PI3K delta, in patients with relapsed or refractory indolent non-Hodgkin lymphoma (Abstract #8526; poster session).


Mantle Cell Lymphoma (MCL)
Final results of a Phase 1 study of idelalisib, a selective inhibitor of PI3K delta in patients with relapsed or refractory mantle cell lymphoma (Abstract #8519; clinical science symposium).
Preliminary results of PI3K delta inhibitor idelalisib treatment in combination with everolimus, bortezomib, or bendamustine/rituximab in patients with previously treated mantle cell lymphoma (Abstract #8501; oral session).


About Study 101-08
Study 101-08 is an open-label, single-arm Phase 2 trial that enrolled 64 treatment- naïve patients ≥65 years old with CLL or small lymphocytic lymphoma (SLL), a less common form of the disease. Patients received intravenous rituximab 375 mg/m2 weekly for eight weeks and oral idelalisib 150 mg twice daily for 48 weeks. The primary endpoint of the study is overall response rate, defined as the proportion of patients achieving a complete or partial response with this regimen (response definitions based on standard criteria). Patients completing 48 weeks of therapy without progression could continue to receive idelalisib in an extension study.

About Idelalisib
Idelalisib is an investigational, targeted, highly selective oral inhibitor of phosphoinositide 3-kinase (PI3K) delta, a molecular target that is critical for the activation, proliferation and survival of B lymphocytes. PI3K delta signaling is hyperactive in many B-cell leukemias and lymphomas and drives proliferation, survival and trafficking to lymphoid tissue. Idelalisib is being developed both as a single agent and in combination with approved and investigational therapies.
Gilead’s clinical development program for idelalisib includes three Phase 3 studies evaluating the drug in combination with approved therapies for patients with previously treated CLL, and two Phase 3 studies of idelalisib in combination with approved therapies for patients with previously treated indolent non-Hodgkin’s lymphoma (iNHL). In addition, combination therapy with idelalisib and GS-9973, Gilead’s novel spleen tyrosine kinase (Syk) inhibitor, is being studied in a Phase 2 trial of patients with relapsed or refractory CLL, iNHL and other lymphoid and hematological malignancies.
Additional information about clinical studies of idelalisib and Gilead’s other investigational cancer agents can be found at www.clinicaltrials.gov. Idelalisib and GS- 9973 are investigational products and their safety and efficacy have not yet been established.

About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Asia Pacific. 

Abstract # 7005


Background: PI3K-delta is critical for activation, proliferation and survival of B cells and plays a role in homing and retention in lymphoid tissues. PI3Kδ signaling is hyperactive in many B-cell malignancies. Idelalisib is a first-in-class, selective oral inhibitor of PI3Kδ. When combined with R in 19 relapsed/refractory patients with CLL, the ORR was 78% (Coutre, ASH 2012). Methods: Treatment-naive pts ≥65 yrs with CLL or SLL were treated with R 375 mg/mweekly x 8 and idelalisib 150 mg bid continuously for 48 weeks (primary study). Pts completing 48 wks w/o progression could continue to receive idelalisib on an extension study. Responses and progression were based on investigator assessment using IWCLL criteria (Hallek, Blood 2008). Results: Data is presented here on the first 50 of 64 pts enrolled, 48 CLL/2 SLL, median age 71 yrs (range: 65-89), M/F 70/30 (%), Rai stage III/IV 10/32 (%), nodes ≥5 cm in 16%, WHO 0/1/2 in 34/64/2 (%); del(17p) in 6 pts and del(11q) in 13 pts. 32 pts completed 48 wks (18 discontinued, 11 due to AE, 4 due to death and 3 other); 30 pts entered the extension study and 26 remain on treatment. The median time on treatment was 16 months (range 0.8-27.5). The ORR was 96% with 4% nonevaluable; median time to response was 1.9 mos (range 1.0-6.5). There have been no on-study relapses. The Kaplan-Meier estimated PFS is 91% at 24 mos. Of note, 6/6 pts with del(17p) responded (1 CR, 5 PR) and 3 remain on treatment for more than 21 months. 13/14 (93%) pts with thrombocytopenia and 12/12 (100%) pts with anemia at baseline responded. Of 20 pts with B symptoms at baseline, 13 (65%) were asymptomatic by 8 wks. Most frequent AEs (total%/ ≥G3%) were diarrhea (including reported as colitis) (46/16), pyrexia (42/4), chills (34/0), fatigue (34/2), rash (34/10), pneumonia (30/20) and nausea (28/0). Elevated ALT/AST was seen in 60%, Gr ≥3 in 22%. Conclusions:Idelalisib + R is highly active, resulting in durable disease control in treatment-naïve older pts with CLL. These results support the further development of idelalisib in frontline CLL. Clinical trial information: NCT01203930.

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1 Comments:

Anonymous Anonymous said...

This is very encouraging news. Personally I would rather live with low level CLL and receive this type of treatment rather than chemo.

However, I am concerned about the side effect issues such as pneumonia.

I was wondering if they are referring to viral or bacteria pneumonia ?

Had any of those receiving treatment received a pneumonia vaccination prior to treatment ?

If vaccinated then what type of pneumonia did they contract ?

This begs the question : Is Idelalisib likely to be a contributor to other infections (as to yet unknown) as happened with Ofatumumab after it had been in use for a while ?

May 25, 2013 at 5:41 AM  

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