On Location Conference Coverage
• Acute myeloid leukemia (not acute
promyelocytic leukemia; 6%)
• Ovarian cancer (6%)
• Sarcoma (5%)
The majority of CML requests were for
ponatinib, the authors explained, because,
at the time of the analysis, ponatinib was
still under restricted access and only available through an IND request.
The FDA received requests from all but
one state, and most requests came from
patients treated at a major university-related
hospital (67%). Six percent were from dedicated children’s hospitals and 0.7 percent
were from Veterans Affairs hospitals.
The median review time for the 1,309
INDs with documented receipt and “proceed” dates was one day, and the mean
review time for all requests was 2.2 days
(3.1 days for single-patient requests and
0.4 days for emergency requests). Notably,
75 percent of INDs were reviewed within
three days.
All but 30 of the single-patient IND
requests were granted within 14 days of
receipt; of the requests that took longer to
grant decisions, 22 had major issues with
documentation, the authors noted.
“OHOP’s review time and approval
of nearly all cancer-related, single-patient
expanded access requests is consistent with
FDA goals to facilitate expanded access,”
the authors concluded. “OHOP is continuing to work to improve this process and
increase transparency to facilitate access for
more patients.”
As part of these efforts, on June 2, 2016,
the FDA finalized its plan to streamline the
process physicians use to request expanded
access to INDs and biologics for their patients. “Access to investigational treatments
requires the active cooperation of the FDA,
industry, and health-care professionals to
be successful,” FDA Commissioner Robert
Califf, MD, said in a statement released
by the agency. “But we know that navigating that process can be challenging and
time-consuming, and we are committed to
reducing the procedural burdens on physicians and patients whenever possible.”
The first part of this plan is the “Individual Patient Expanded Access Investigational New Drug Application - Form FDA
3926.” According to the FDA, the form is
much shorter than the previous version
used for individual patient expanded access
requests and is designed specifically for these
requests.
REFERENCE
Lemery SJ, Mailankody S, Kazandjian D, et al. Food and Drug
Administration analysis of 1332 single patient and emergency use
expanded access (compassionate use) requests for patients with cancer
over a duration of three years (2012-2014). Abstract #6523. Presented
at the 2016 American Society of Clinical Oncology Annual Meeting, June
4, 2016; Chicago, IL.
Acalabrutinib Safe in Patients with Previously
Untreated Chronic Lymphocytic Leukemia
Preliminary results from a phase I/
II study of the second-generation
Bruton’s tyrosine kinase (BTK)
inhibitor acalabrutinib in patients
with previously untreated chronic
lymphocytic leukemia (CLL)
showed that the drug was well
tolerated and had a favorable safety
profile in the majority of patients.
John C. Byrd, MD, from The Ohio
State University Comprehensive
Cancer Center, and authors presented the study’s findings at the
ASCO Annual Meeting.
“BTK is a critical therapeutic target
in CLL,” Dr. Byrd and co-authors explained. “Acalabrutinib is an irreversible,
selective BTK inhibitor that has demonstrated clinical efficacy in relapsed CLL.”
Based on those results, the investigators
evaluated the safety of acalabrutinib in
the front-line setting. Of note, the U.S.
Food and Drug Administration approved ibrutinib, a first-generation BTK
inhibitor, for the first-line treatment of
CLL in March 2016.
The study enrolled patients with
previously untreated CLL who met
the following inclusion criteria:
• International Workshop
on Chronic Lymphocytic
Leukemia 2008 criteria for
treatment, irrespective of any
cytope nias
• Eastern Cooperative
Oncology Group
performance status of 0-2
• Contraindications for
chemoimmunotherapy
44
ASH Clinical News
Patients were excluded if they had
significant cardiovascular disease.
Patients received oral acalabrutinib 100 mg twice daily (n=37)
or 200 mg once daily (n=37). The
median patient age was 64 years
(range = 48-85 years), most had
an unmutated IGHV gene (57%;
n=38/67), and 47 percent had bulky
lymph nodes (≥5 cm).
The median time on the study for
all 74 patients was 11 months (range
= 1-15 months). The analysis included
data up to December 7, 2015, when,
72 patients were evaluable.
“In patients with previously
untreated CLL, [we observed] a
favorable safety profile and high response rate [97%] with acalabrutinib
therapy,” the authors wrote.
Most adverse events (AEs) were
grade ≤2, including the following
grade 1/2 AEs:
• headache (42%)
• diarrhea (35%)
• arthralgia (22%)
• contusion (18%)
• nausea (18%)
• weight gain (18%)
Grade 3/4 AEs that occurred in ≥2
patients included syncope (n=2)
and hypertension (n=2). One grade
5 pneumonia was reported, and one
grade 3 upper gastrointestinal bleed
occurred.
Treatment-related lymphocytosis
occurred in 53 percent of patients
(n=39/74) and resolved in 97 percent
of those patients (n=38/39). Lymphocytosis peaked at a median of
one week and was resolved by a
median of seven weeks (range = 3-15
weeks).
After a median time to response
of two months (range = 2-8 months),
the best overall response rate (the
study’s secondary endpoint) was 96
percent:
• 86% achieved a partial
response (PR)
• 10% achieved a PR with
lymphocytosis (PRL)
• 4% had stable disease
Of those who achieved a response
of PRL or better, with 12 months
of follow-up, no death or disease
progression was reported.
The median progression-free
survival had not been reached at the
time of data cut-off. Dr. Byrd and coauthors also noted that no CLL progression or Richter’s transformations
have occurred. This clinical activity
was observed in both acalabrutinib
dosing cohorts, they added.
Based on the early results
from this study, a global phase III
trial comparing acalabrutinib plus
obinutuzumab versus chlorambucil
in patients with previously untreated
CLL is ongoing.
REFERENCE
Byrd JC, Jones JA, Furman RR, et al. Acalabrutinib, a secondgeneration bruton tyrosine kinase (Btk) inhibitor, in previously
untreated chronic lymphocytic leukemia (CLL). Abstract #7521.
Presented at the 2016 American Society of Clinical Oncology
Annual Meeting, June 6, 2016; Chicago, IL
July 2016