Olema Oncology Announces OP-1250 Demonstrates Attractive Combinability with CDK 4/6 Inhibitor Palbociclib in Phase 1b Dose Escalation Study
December 07 2022 - 3:37PM
Olema Pharmaceuticals, Inc. (“Olema”, “Olema Oncology”, or the
“Company”, Nasdaq: OLMA) today announced results from a Phase 1b
dose escalation clinical study of OP-1250, the Company’s complete
estrogen receptor (ER) antagonist (CERAN) and selective ER degrader
(SERD), in combination with palbociclib, a CDK 4/6 inhibitor for
the treatment of metastatic ER+/HER2- breast cancer. These results,
as of September 12, 2022, were presented today in a poster session
at the 2022 San Antonio Breast Cancer Symposium (SABCS) at the
Henry B. Gonzalez Convention Center in San Antonio, Texas.
The poster, titled “A Phase 1b/2 dose escalation and dose
expansion study of OP-1250, an oral complete estrogen receptor
antagonist (CERAN)/selective estrogen receptor degrader (SERD), in
combination with the CDK4/6 inhibitor palbociclib in patients with
advanced and/or metastatic estrogen receptor (ER)-positive,
HER2-negative breast cancer (OP-1250-002; NCT05266105)”,
highlighted that:
- Across 12 patients, the combination of up to 120 mg of OP-1250
with 125 mg of palbociclib is safe and well-tolerated with no
drug-drug interaction (DDI), no induced metabolism of palbociclib,
and exposure of OP-1250 in combination with palbociclib is
consistent with the observed monotherapy OP-1250 exposure
levels.
- There was no dose-related increase in the incidence or severity
of adverse events, and neutropenia events observed are consistent
with the expected profile of palbociclib plus endocrine
therapy.
“OP-1250 continues to demonstrate its potential to be the
best-in-class endocrine therapy for ER+/HER2- breast cancer. The
results we presented today validate the opportunity to combine
OP-1250 with a CDK 4/6 inhibitor for the treatment of metastatic
breast cancer,” said Sean P. Bohen, M.D., Ph.D., President and
Chief Executive Officer of Olema Oncology. “These data show that
OP-1250 combines well with palbociclib, including a tolerability
profile consistent with palbociclib in combination with an
aromatase inhibitor or fulvestrant, no drug-drug interaction, and
no induced metabolism of palbociclib. We are actively enrolling our
Phase 2 dose expansion at 120 mg of OP-1250 in combination with
palbociclib to support a future Phase 3 trial of OP-1250 in
combination with a CDK 4/6 inhibitor.”
Phase 1b Clinical Results
Enrollment
As of the data cut-off of September 12, 2022, 12 patients with
recurrent, locally advanced or metastatic ER+/HER2- breast cancer
were treated across four dose escalation cohorts: three patients
per cohort dosed at 30, 60, 90, and 120 mg in combination with
palbociclib 125 mg. Ten of the 12 patients received prior therapy
for advanced disease, including eight patients who had received
prior CDK4/6 inhibitors and nine patients who received prior
endocrine therapy for advanced disease. Of 11 patients whose
circulating tumor DNA (ctDNA) was assessed, 36% had activating
mutations in ESR1 at baseline.
Pharmacokinetics
OP-1250 demonstrated favorable pharmacokinetics characterized by
high oral bioavailability, dose proportional exposure and a long
half-life of eight days, with steady-state plasma levels showing
minimal peak-to-trough variability, enabling consistent inhibition
of ER for the full dosing interval. There was no observed DDI
between palbociclib and OP-1250 in the dose range of 30 mg to 120
mg. Palbociclib did not affect OP-1250 drug exposures compared to
monotherapy dosing, and OP-1250 had no effect on palbociclib 125 mg
drug exposures when compared to published concentrations.
Safety and Tolerability
Treatment with OP-1250 up to the Recommended Phase 2 Dose (RP2D)
of 120 mg was safe and well tolerated with no dose-limiting
toxicities, and maximum tolerated dose (MTD) was not reached. The
majority of treatment-emergent adverse events (TEAEs) were Grade 1
or 2, and increasing the dose did not show an increase in frequency
of events. OP-1250 was not dose-reduced in any patients, and no
patients discontinued treatment with OP-1250 due to an adverse
event, including neutropenia. Neutropenia events observed were
consistent with the expected profile of palbociclib plus an
endocrine therapy. There was no Grade 4 neutropenia, and eight of
12 patients reported Grade 3 neutropenia, a rate which is
consistent with the FDA-approved label of palbociclib plus an
endocrine agent.
Pre-clinical Combination Study Results
A second poster, titled “Combination of complete estrogen
receptor antagonist, OP-1250, and CDK4/6 inhibitors enhances tumor
suppression and inhibition of cell cycle-related gene expression”,
was presented at SABCS and highlighted pre-clinical data showing
that the combination of OP-1250 and CDK4/6 inhibitors, palbociclib
and ribociclib, results in greater suppression of transcription
related to cell cycle progression than the sum of
monotherapies.
Copies of the posters are available on Olema’s website under the
Science section.
About Olema OncologyOlema Oncology is a
clinical-stage biopharmaceutical company focused on the discovery,
development and commercialization of targeted therapies for women’s
cancers. Olema’s lead product candidate, OP-1250, is a proprietary,
orally-available small molecule with dual activity as both a
complete estrogen receptor (ER) antagonist (CERAN) and a selective
ER degrader (SERD). It is currently being evaluated both as a
single agent in an ongoing Phase 2 clinical trial, and in
combination with CDK 4/6 inhibitors (palbociclib and ribociclib)
and a PI3Ka inhibitor (alpelisib), in patients with recurrent,
locally advanced or metastatic ER-positive (ER+), human epidermal
growth factor receptor 2-negative (HER2-) breast cancer. OP-1250
has been granted FDA Fast Track designation. Olema is headquartered
in San Francisco and has operations in Cambridge,
Massachusetts.
IR Contact:Courtney Dugan, Vice President, Investor
Relations and Communications ir@olema.com
Media Contact:Ignacio Guerrero-Ros, Ph.D., Russo
Partners646-942-5604ignacio.guerrero-ros@russopartnersllc.com
Olema Pharmaceuticals (NASDAQ:OLMA)
Historical Stock Chart
From Jun 2024 to Jul 2024
Olema Pharmaceuticals (NASDAQ:OLMA)
Historical Stock Chart
From Jul 2023 to Jul 2024