Clovis Oncology (NASDAQ:CLVS) announced today updated findings from the
Phase 1 portion of its ongoing Phase 1/2 clinical study of CO-1686, the
Company’s novel, oral, targeted covalent (irreversible) inhibitor of
mutant forms of the epidermal growth factor receptor (EGFR) for the
treatment of non-small cell lung cancer in patients with initial
activating EGFR mutations as well as the dominant resistance mutation
T790M. Interim results from the Phase 1 dose-escalation portion of this
Phase 1/2 study are being presented today in an oral presentation by Dr.
Heather Wakelee at the 4th European Lung Cancer Conference
(ELCC) in Geneva.
“These data are completely consistent with what I have seen personally
in my own patients,” said Professor Jean-Charles Soria, Professor of
Medicine and Medical Oncology at Paris University XI and cancer
specialist at Gustave Roussy Institute and the European lead
investigator for the Phase 1/2 study of CO-1686. “CO-1686 provides
meaningful and long-term benefit for patients who until now have had
limited, if any, options. I am very enthusiastic about participating in
the continued development of this agent.”
“One of the issues with oncogene-targeted therapies is that while
initial response rates can be promising, these responses can be
short-lived,” said Patrick J. Mahaffy, President and CEO of Clovis
Oncology. “In contrast, as CO-1686 Phase 1 data extend and mature, we
see both a consistency of response rate that is very encouraging as well
as an impressive initial duration of clinical benefit. Patients in
general benefit from, and stay on, CO-1686 for a prolonged period of
time. We are also pleased that we can deliver this long-term benefit
with very good tolerability. Given the observed durability of clinical
benefit we are increasingly optimistic about the potential of CO-1686
not only to deliver impressive response rates, but also meaningful
progression-free survival in both first- and second-line patients.”
The Phase 1 dose escalation portion of the study is being conducted in
the United States, France and Australia in patients with metastatic or
unresectable recurrent NSCLC and a documented EGFR mutation. Patients
were not required to be T790M positive for the Phase 1 portion of the
study but had to have progressed on prior EGFR-directed tyrosine kinase
inhibitor (TKI) therapy (prior chemotherapy was also allowed).
Approximately one hundred patients have been treated with CO-1686 to
date across all dosing cohorts in the Phase 1 portion of the trial.
Emerging data from the first 62 patients treated with CO-1686 at
efficacious doses (comprising patients treated with 900mg BID of
freebase or any dose of the hydrobromide salt (HBr) formulation) were
presented today at ELCC. Of these 62 patients, 22 are
centrally-confirmed T790M positive, 12 are centrally-confirmed T790M
negative, seven have as yet unknown T790M status and the remaining are
non-evaluable, primarily because they have not yet had their first scan.
Patients on study were heavily pretreated prior to receiving CO-1686; 73
percent of patients across all doses had immediately progressed on TKI
therapy prior to CO-1686 treatment. The median number of previous lines
of therapy across patients at all doses was three; the median number of
previous TKI lines was two.
Evidence of Activity
In the 22 evaluable T790M positive patients across efficacious dose
levels, 14 RECIST partial responses (PRs) have been observed to date,
for a 64 percent objective response rate (ORR). Ten of the 14 patients
(71 percent) started CO-1686 therapy immediately following progression
on a prior TKI. Twenty of the 22 evaluable T790M positive patients, or
91 percent, have experienced stable disease or a PR.
In a broader population of 29 evaluable T790M positive and T790M
currently unknown patients, 15 RECIST PRs have been observed to date,
for a 52 percent response rate. Twenty-six of the 29 evaluable 790M
positive and T790M currently unknown patients, or 90 percent, have
experienced stable disease or a PR. These data will be updated if and as
the T790M status of the unconfirmed patients are centrally determined.
The median duration of response cannot yet be estimated in the T790M
positive patients. However, PFS greater than six months has been
observed in evaluable T790M positive heavily-pretreated patients and the
median has not yet been reached. In contrast, PFS in T790M negative
patients is shorter, with a median of three months.
Five of nine evaluable patients, or 56 percent, dosed initially with
900mg BID of freebase and now on the HBr formulation remain on drug with
continuing PRs, and 35 of the 43 total patients dosed with the HBr
formulation, or 81 percent, remain on drug.
Safety and Tolerability
CO-1686 is well-tolerated, with only one patient who discontinued
treatment with CO-1686 due to adverse events. There was no evidence of
systemic wild-type EGFR inhibition. The most common adverse events were
hyperglycemia, nausea, diarrhea, decreased appetite and vomiting, and
these were mostly grade 1 in severity. The most common grade 3 adverse
event was hyperglycemia, which was observed in 19 percent of patients.
Hyperglycemia, when observed and requiring treatment, is typically
asymptomatic and managed with a commonly prescribed single oral agent.
Presentation Details
The presentation, titled “Phase 1 evaluation of CO-1686, an
irreversible, mutant-selective inhibitor of EGFR mutations (activating
and T790M)”, was presented on Thursday, March 27, during the session
titled “Advanced Disease with Targeted Agents” from 9:00 -10:30am. The
presentation is available at www.clovisoncology.com.
CO-1686 Clinical Development
The Company is currently enrolling two Phase 2 expansion cohorts of its
Phase 1/2 study in EGFR mutant patients who have tested positive for the
T790M mutation. The first cohort includes approximately 150 to 200
patients directly after progression on their first and only TKI therapy,
and is exploring doses of 500mg, 750mg and 1000mg BID. The second cohort
includes approximately 150 later-line patients directly after
progression on their second or later TKI therapy or subsequent
chemotherapy, and is exploring doses of 750mg and 1000mg BID. These
cohorts are enrolling in the United States, Europe and Australia. Data
from the expansion cohorts, combined with data from TIGER2, are now
expected to serve as the basis of an NDA submission for CO-1686 during
2015.
Clovis expects to initiate three registration studies in the TIGER
(Third-generation Inhibitor of Mutant EGFR in Lung Cancer) program
during 2014. The TIGER2 study, in T790M positive patients directly after
progression on their first and only TKI therapy, is planned to initiate
by the end of Q2 2014, as will the Phase 2 portion of the TIGER1 study,
which is a randomized Phase 2/3 registration study of CO-1686 vs.
erlotinib in newly-diagnosed EGFR mutant patients who have not had TKI
therapy but who may have received one type of chemotherapy. The TIGER3
study is a randomized, comparative study versus chemotherapy in
later-line patients, expected to initiate during the second half of
2014. This is a modification of the previous planned TIGER3 study to
bring forward the implementation of a comparative study versus
conventional chemotherapy.
In addition, the Company initiated its Phase 1 study in Japan earlier
this quarter.
Conference Call Details
Clovis will hold a conference call to discuss the ELCC data presentation
this morning, March 27, at 8:30 a.m. ET. The conference call will be
simultaneously webcast on the Company’s web site at www.clovisoncology.com,
and archived for future review. Dial-in numbers for the conference call
are as follows: US participants’ 866.318.8612, International
participants’ 617.399.5131, passcode: 83903968.
About CO-1686
CO-1686 is a novel, oral, targeted covalent (irreversible) inhibitor of
the cancer-causing mutant forms of epidermal growth factor receptor
(EGFR) currently being studied for the treatment of non-small cell lung
cancer (NSCLC). CO-1686 was designed to selectively target both the
initial activating EGFR mutations as well as the T790M resistance
mutation, while sparing wild-type, or “normal” EGFR at anticipated
therapeutic doses. Accordingly, it has the potential to treat NSCLC
patients with EGFR mutations both as a first-line or second-line
treatment with a reduced toxicity profile compared to current EGFR
inhibitor therapies. The Company is currently studying CO-1686 in Phase
2 expansion cohorts of NSCLC patients with activating EGFR mutations who
have failed initial EGFR-directed therapy and have developed the T790M
resistance mutation.
About Clovis Oncology
Clovis Oncology, Inc. is a biopharmaceutical company focused on
acquiring, developing and commercializing innovative anti-cancer agents
in the U.S., Europe and additional international markets. Clovis
Oncology targets development programs at specific subsets of cancer
populations, and simultaneously develops diagnostic tools that direct a
compound in development to the population that is most likely to benefit
from its use. Clovis Oncology is headquartered in Boulder, Colorado.
To the extent that statements contained in this press release are not
descriptions of historical facts regarding Clovis Oncology, they are
forward-looking statements reflecting the current beliefs and
expectations of management made pursuant to the safe harbor provisions
of the Private Securities Litigation Reform Act of 1995. Such
forward-looking statements involve substantial risks and uncertainties
that could cause our clinical development programs, future results,
performance or achievements to differ significantly from those expressed
or implied by the forward-looking statements. Such risks and
uncertainties include, among others, the uncertainties inherent in our
clinical development programs for our drug candidates, the corresponding
development pathways of our companion diagnostics, actions by the FDA,
the EMA or other regulatory authorities regarding whether to approve
drug applications that may be filed, as well as their decisions
regarding drug labeling, and other matters that could affect the
availability or commercial potential of our drug candidates or companion
diagnostics, including competitive developments. Clovis Oncology
does not undertake to update or revise any forward-looking statements. A
further description of risks and uncertainties can be found in Clovis
Oncology’s filings with the Securities and Exchange Commission,
including its Annual Report on Form 10-K and its reports on Form 10-Q
and Form 8-K.
Copyright Business Wire 2014