Olema Pharmaceuticals, Inc. (“Olema” or “Olema Oncology,” Nasdaq:
OLMA), a clinical-stage biopharmaceutical company focused on the
discovery, development and commercialization of targeted therapies
for women’s cancers, today announced interim results from an
ongoing Phase 1b/2 clinical study of palazestrant (OP-1250) in
combination with CDK4/6 inhibitor ribociclib for the treatment of
ER+/HER2- metastatic breast cancer. These results, as of the data
cut-off of March 13, 2024, will be presented on May 16, 2024, in a
poster session at the 2024 ESMO Breast Cancer Annual Congress in
Berlin, Germany (ESMO Breast).
The poster, titled “A Phase 1b/2 Study of Palazestrant (OP-1250)
in Combination with Ribociclib in Patients with Estrogen
Receptor-Positive, Human Epidermal Growth Factor Receptor
2-Negative, Advanced and/or Metastatic Breast Cancer”, highlighted
that:
- Across 50 treated patients, the
combination of up to 120 mg of palazestrant with the full and
approved dose of 600 mg of ribociclib daily was well tolerated,
with no new safety signals or enhancement of toxicity and an
overall safety profile consistent with the established safety
profile of ribociclib plus an endocrine therapy.
- Palazestrant did not affect
ribociclib drug exposure and ribociclib had no clinically
meaningful effect on palazestrant drug exposure.
- Promising preliminary efficacy was
observed to date with a clinical benefit rate (CBR) of 85% across
all CBR-eligible patients (11/13), 83% in ESR1-mutant patients
(5/6), 86% in ESR1-wild-type patients (6/7), and 83% in prior
CDK4/6 inhibitor patients (10/12).
- Partial responses were observed in
five patients through the data cut-off (2 confirmed, 3 unconfirmed)
among 23 response-evaluable patients.
- Findings from this study support the
continued clinical development of palazestrant in combination with
ribociclib for the first-line treatment of ER+/HER2- advanced or
metastatic breast cancer.
“The data we are presenting at the ESMO Breast Cancer Annual
Congress in Berlin add further support to our thesis that
palazestrant possesses key characteristics that make it a potential
backbone endocrine therapy of preference for ER+/HER2- breast
cancer, both as a monotherapy and in combination with other
targeted agents,” said Sean P. Bohen, M.D., Ph.D., President and
Chief Executive Officer of Olema Oncology. “We are grateful to the
approximately 300 women to date that have participated across our
clinical trials. We are excited with the progress we are making,
and we look forward to advancing toward our goal of transforming
the endocrine therapy standard of care for breast cancer.”
Phase 1b/2 Clinical Study Results
Enrollment
As of the data cut-off of March 13, 2024, 50 patients with
recurrent, locally advanced or metastatic ER+/HER2- breast cancer
with at least four weeks of follow-up were treated with
palazestrant (3 patients each at 30 mg once daily and 60 mg once
daily, 44 patients at the palazestrant recommended Phase 2 dose
(RP2D) of 120 mg once daily) plus ribociclib 600 mg once daily
(three weeks followed by one week off treatment). The majority of
patients (37 or 74%) were 2nd/3rd line+, with 37 (74%) patients
having received prior endocrine therapy for metastatic breast
cancer, 35 (70%) patients having received prior CDK4/6 inhibitors
(11 or 22% having received two prior lines of CDK4/6 inhibitors),
and nine (18%) patients having received chemotherapy for metastatic
breast cancer. Of 48 patients whose circulating tumor DNA (ctDNA)
was assessed as of the data cut-off, 27% had activating mutations
in ESR1 at baseline. The study is now fully enrolled with 60
patients.
Pharmacokinetics
Palazestrant demonstrated favorable pharmacokinetics
characterized by high oral bioavailability, dose proportional
exposure and a half-life of eight days as a single agent, with
steady-state plasma levels showing minimal peak-to-trough
variability enabling consistent inhibition of ER for the full
dosing interval. Palazestrant did not affect ribociclib 600 mg drug
exposure when compared with published exposure data for
single-agent ribociclib. Steady-state trough values showed no
clinically significant difference between the combination and
single-agent palazestrant.
Safety and Tolerability
Treatment with palazestrant up to the RP2D of 120 mg was well
tolerated with no dose-limiting toxicities, and the maximum
tolerated dose (MTD) was not reached. The majority of
treatment-emergent adverse events (TEAEs) were Grade 1 or 2, and
the severity and incidence of adverse events were consistent with
the expected safety profile of ribociclib plus endocrine therapy.
Ten patients had dose reduction of ribociclib only, due to QTcF
prolongation (n=4), neutropenia (n=4), or fatigue (n=2). No
patients discontinued palazestrant due to a treatment-related
adverse event, and two patients discontinued ribociclib for
neutropenia without discontinuation of palazestrant in the 120 mg
cohort. Neutropenia was reversible in all patients and the timing
was consistent with ribociclib-related neutropenia.
Efficacy
In a maturing dataset, palazestrant showed anti-tumor activity
and prolonged disease stabilization in patients both with ESR1
wild-type and ESR1 activating mutations at baseline, and in those
previously treated with one or two lines of CDK4/6 inhibitors.
Partial responses were observed in five patients (two confirmed,
three unconfirmed as of data cut-off) out of 23 response-evaluable
patients. Across patients who were CBR-eligible, the CBR was 85%
(11/13) for all patients, 83% (5/6) for patients with ESR1
mutations, 86% (6/7) for patients that were ESR1 wild-type, and for
CDK4/6i-pretreated patients the CBR was 83% (10/12). The longest
duration on treatment is 44 weeks through the data cut-off, and 66%
(33/50) of patients in this data set remain on treatment as of the
data cut-off date.
A copy of the poster will be available on Olema’s website under
the Science section.
Company Investor Webcast and Conference
Call
Olema will host a webcast and conference call for analysts and
investors to review the data being presented at ESMO Breast Cancer
Annual Congress 2024 today, Wednesday, May 15, 2024, at 8:00 a.m.
ET (2:00 p.m. CEST). Please register for the webcast by visiting
the Investors & Media section of Olema’s website at
olema.com.
About Palazestrant (OP-1250)
Palazestrant (OP-1250) is a novel, orally-available small
molecule with dual activity as both a complete estrogen receptor
(ER) antagonist (CERAN) and selective ER degrader (SERD). It is
currently being investigated in patients with recurrent, locally
advanced or metastatic ER-positive (ER+), human epidermal growth
factor receptor 2-negative (HER2-) breast cancer. In clinical
studies, palazestrant completely blocks ER-driven transcriptional
activity in both wild-type and mutant forms of metastatic ER+
breast cancer and has demonstrated anti-tumor efficacy along with
attractive pharmacokinetics and exposure, favorable tolerability,
CNS penetration, and combinability with CDK4/6 inhibitors.
Palazestrant has been granted U.S. Food and Drug Administration
(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. It is being evaluated both as
a single agent in an ongoing Phase 3 clinical trial, OPERA-01, and
in Phase 1/2 combination studies with CDK4/6 inhibitors
(palbociclib and ribociclib), a PI3Ka inhibitor (alpelisib), and an
mTOR inhibitor (everolimus). For more information, please visit
www.opera01study.com.
About Olema Oncology
Olema Oncology is a clinical-stage biopharmaceutical company
committed to transforming the standard of care and improving
outcomes for women living with cancer. Olema is advancing a
pipeline of novel therapies by leveraging our deep understanding of
endocrine-driven cancers, nuclear receptors, and mechanisms of
acquired resistance. In addition to our lead product candidate,
palazestrant (OP-1250), a proprietary, orally-available complete
estrogen receptor (ER) antagonist (CERAN) and a selective ER
degrader (SERD), Olema is developing a potent KAT6 inhibitor
(OP-3136). Olema is headquartered in San Francisco and has
operations in Cambridge, Massachusetts. For more information,
please visit us at www.olema.com.
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 and
Section 21E of the Securities Exchange Act of 1934. 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
palazestrant, the development of palazestrant, the initiation and
timing of clinical trials, palazestrant’s combinability with other
drugs, the potential of palazestrant to become a backbone endocrine
therapy in the treatment of ER+/HER2- metastatic breast cancer, and
Olema’s potential to transform the endocrine therapy standard of
care treatments 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 Quarterly Report on Form 10-Q for
the quarter ended March 31, 2024, and other 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, including in
the event that actual results differ materially from those
anticipated in the forward-looking statements.
Contact:Geoffrey Mogilner, Vice President, Investor Relations
and Communicationsir@olema.com
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