Olema Pharmaceuticals, Inc. (“Olema”, “Olema Oncology”, or the
“Company”, Nasdaq: OLMA) today announced interim results from an
ongoing Phase 1b/2 clinical study of OP-1250, the Company’s
complete estrogen receptor (ER) antagonist (CERAN) and selective ER
degrader (SERD), in combination with palbociclib, a CDK4/6
inhibitor, for the treatment of ER+/HER2- metastatic breast cancer.
These results, as of March 8, 2023, were presented today in a
poster session at the 2023 ESMO Breast Cancer Annual Congress in
Berlin, Germany.
The poster, titled “A Phase 1b/2 Study of OP-1250, an Oral
Complete Estrogen Receptor Antagonist (CERAN) and Selective ER
Degrader (SERD) with Palbociclib in Patients with Advanced or
Metastatic HR+/HER2- Breast Cancer”, highlighted that:
- Across 29 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 both palbociclib and
OP-1250 in combination with each other was consistent with the
observed monotherapy exposure levels.
- No dose-related increases in the
incidence, severity, or timing of adverse events were observed, and
neutropenia events observed were consistent with the expected
profile of palbociclib plus endocrine therapy.
- Tumor responses and prolonged
disease stabilization were observed in this group of patients,
including in those previously exposed to palbociclib and other
CDK4/6 inhibitors.
“We are very pleased with our emerging combination clinical
results of OP-1250 with palbociclib,” said Sean P. Bohen, M.D.,
Ph.D., President and Chief Executive Officer of Olema Oncology.
“The findings presented today support the potential for OP-1250 to
become a best-in-class endocrine therapy in the first-line
treatment of ER+/HER2- metastatic breast cancer. OP-1250, in
combination with palbociclib, did not display the drug-drug
interactions or increased toxicity that have been observed with
some novel endocrine therapies.”
Interim Phase 1b/2 Clinical Results
Enrollment
As of the data cut-off of March 8, 2023, 29 patients with
recurrent, locally advanced or metastatic ER+/HER2- breast cancer
were treated. In the dose-escalation part, 12 patients were
enrolled across four cohorts: three patients per cohort dosed at
30, 60, 90, and 120 mg in combination with palbociclib 125 mg. In
the dose-expansion part (ongoing), patients received 120 mg OP-1250
plus palbociclib 125 mg. Seventeen patients had been enrolled in
the dose expansion at the time of data cut-off, with a total
planned enrollment of approximately 45 patients. The majority of
patients (27 or 93%) were 2/3 line, with 25 (86%) patients having
received prior endocrine therapy for advanced disease, 20 (69%)
patients having received prior CDK4/6 inhibitors including prior
palbociclib, and six (21%) patients having received chemotherapy in
the advanced setting. Of 18 patients whose circulating tumor DNA
(ctDNA) was assessed as of the data cut-off, 44% 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 for
single-agent palbociclib.
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. The majority of treatment-emergent adverse events
(TEAEs) were Grade 1 or 2, and there were no dose-related increases
in incidence or severity of TEAEs. 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. Neutropenia was reversible in all
patients and the timing was consistent with palbociclib-related
neutropenia.
Efficacy
In a maturing dataset, anti-tumor activity and prolonged disease
stabilization was demonstrated in patients previously treated with
CDK4/6 inhibitors, including palbociclib. Partial responses were
observed in five patients (one confirmed, four unconfirmed as of
data cut-off) with a clinical benefit rate to date of 42% (5/12
CBR-eligible patients). Fifty-nine percent of patients remain on
treatment as of the data cut-off date with additional enrollment
ongoing.
A copy of the poster is 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 CDK4/6 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 for the treatment of ER+/HER2-
metastatic breast cancer that has progressed following one or more
lines of endocrine therapy with at least one line given in
combination with a CDK4/6 inhibitor. Olema is headquartered in San
Francisco and has operations in Cambridge, Massachusetts.
Forward Looking Statements
Statements contained in this press release regarding matters
that are not historical facts are “forward-looking statements”
within the meaning of Section 27A of the Securities Act of 1933, as
amended, and Section 21E of the Securities Exchange Act of 1934, as
amended. Words such as “anticipate,” “expect,” “will,” “may,”
“goal,” “potential” and similar expressions (as well as other words
or expressions referencing future events, conditions or
circumstances) are intended to identify forward-looking statements.
These statements include those related to the potential beneficial
characteristics, safety, tolerability, efficacy, and therapeutic
effects of OP-1250, the development of OP-1250, OP-1250's
combinability with other drugs, and the potential of OP-1250 to
become a best-in-class endocrine therapy in the first-line
treatment of ER+/HER2- metastatic breast cancer or significantly
improve endocrine therapy for women living with ER+/HER2-
metastatic breast cancer. Because such statements deal with future
events and are based on Olema’s current expectations, they are
subject to various risks and uncertainties, and actual results,
performance or achievements of Olema could differ materially from
those described in or implied by the statements in this press
release. These forward-looking statements are subject to risks and
uncertainties, including, without limitation, those discussed in
the section titled “Risk Factors” in Olema’s Annual Report on Form
10-Q for the quarter ended March 31, 2023, and future filings and
reports that Olema makes from time to time with the U.S. Securities
and Exchange Commission. Except as required by law, Olema assumes
no obligation to update these forward-looking statements or to
update the reasons if actual results differ materially from those
anticipated in the forward-looking statements.
IR Contact:Shane Kovacs, Chief Operating and
Financial Officerir@olema.com
Media Contact:Ignacio Guerrero-Ros, Ph.D., Russo
Partnersignacio.guerrero-ros@russopartnersllc.com
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