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PATIENT TREATED WITH CO-1686
news + research
• 3 previous
immediately before CO-1686
• 625 mg BID
A Double Dose of Promising
UCLA scientists report that two new experimental drugs have shown
great promise in the treatment of patients with non-small-cell lung
cancer, which accounts for about 85 percent of all lung cancers.
The drugs — ramucirumab and CO-1686 — were shown in separate
clinical trials to increase survival times with fewer toxic side effects than
standard treatments. The ﬁndings of both trials were presented at
the annual meeting of the American Society of Clinical Oncology.
Edward Garon, MD (FEL ’06), assistant professor of hematology-
oncology, conducted an extensive multi-year Phase 3 clinical trial
testing ramucirumab in a population of 1,253 patients whose cancers
had progressed during or after ﬁrst-line chemotherapy treatment.
Ramucirumab is an antibody that targets VEGFR-2, an extracellular
protein that is important in the formation of the blood vessels
that support cancer cells. Patients were given ramucirumab in
combination with docetexal, a clinically approved chemotherapy
drug considered the cornerstone of second-line treatment in
advanced non-small-cell lung cancer.
Tumors shrank signiﬁcantly in 23 percent of patients receiving
ramucirumab. The drug is the ﬁrst new therapy for previously treated non-
small-cell lung cancer patients to improve overall survival, when added
to standard therapy with ﬁndings showing a disease-progression-free
survival rate of 4.5 months and median overall survival of 10.5 months.
• 82% target lesion
reduction at C2
• CNS lesion
Scans show how therapy with CO-1686 has diminished tumors in lungs of patient with
T790M mutation, as well as reduced tumors in metastases that have spread to the brain.
Graphic: Courtesy of Dr. Jonathan Goldman
Another class of targeted drugs being investigated is EGFR
(epidermal growth factor receptor) tyrosine kinase inhibitors. Recent
studies, however, have shown that when a patient develops resistance
to EGFR inhibitors, more than half the time it is due to the emergence
of a new “gatekeeper” mutation, called T790M. CO-1686 is an
investigational drug that has been discovered to selectively target
both the initial EGFR mutations and the T790M-resistance mutation.
Jonathan Goldman, MD (FEL ’08), assistant professor of
hematology-oncology, was among the leaders of a study of 88
patients with advanced non-small-cell lung cancer who had
previously been treated with an EGFR inhibitor and had developed
resistance. In a Phase 1 trial, CO-1686 was administered
continuously to the patients in 21-day cycles. Response to the
drug was seen in 58 percent of the patients. Treatment-related
side effects were for the most part mild and manageable.
“Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line
treatment of stage IV non-small-cell lung cancer after disease progression
on platinum-based therapy (REVEL): a multicentre, double-blind,
randomized phase 3 trial,” The Lancet, June 2014
The Healing Heart
There has been debate over the question
of whether or not heart muscle can
regenerate itself. Now, UCLA scientists
have provided an answer: yes. A study
by Reza Ardehali, MD, PhD, assistant
professor of cardiology, and colleagues has
demonstrated the ﬁrst direct measure of
heart-muscle cells renewing themselves.
The ﬁndings have important implications
for future research that could lead to
the regeneration of heart tissue to repair
damage caused by disease or heart attack.
Illustration: Brad Yeo
C2 It was initially believed that heart-muscle
cells, or cardiomyocytes, were unable to
replicate themselves and that their total
number was set at birth; however, research
over the past two decades has indicated
that these cardiac cells have limited
proliferative activity, though there has been
no clear agreement within the scientific
community as to why and how much.
In part, the indirect methods used to
measure this potential cell division have
been difficult, and at times inaccurate,
preventing a scientific consensus. Some
groups of researchers used carbon dating to
detect the age of human cardiomyocytes to