Olema Oncology Presents Updated Clinical Results for Palazestrant in Combination with Ribociclib at the San Antonio Breast Cancer Symposium
Olema Oncology announced updated clinical results for palazestrant combined with ribociclib in treating ER+/HER2- advanced or metastatic breast cancer. With a 12-month median follow-up, the study showed promising results with median progression-free survival (PFS) not yet reached. The 6-month PFS rate was 73% overall, with 81% in ESR1 mutation patients and 70% in ESR1 wild-type patients.
The Phase 1b/2 study included 62 patients, with 56 receiving the recommended Phase 2 dose. The combination demonstrated favorable tolerability and safety profile consistent with ribociclib and endocrine therapy. Notable outcomes include a 76% clinical benefit rate across all patients and 27% objective response rate in patients with measurable disease.
Olema Oncology ha annunciato risultati clinici aggiornati per il palazestrant combinato con ribociclib nel trattamento del carcinoma mammario avanzato o metastatico ER+/HER2-. Con un follow-up mediano di 12 mesi, lo studio ha mostrato risultati promettenti con una sopravvivenza libera da progressione mediana (PFS) non ancora raggiunta. Il tasso di PFS a 6 mesi è stato del 73% in generale, con l'81% nei pazienti con mutazione ESR1 e il 70% nei pazienti di tipo selvatico ESR1.
Lo studio di Fase 1b/2 ha incluso 62 pazienti, di cui 56 hanno ricevuto la dose raccomandata di Fase 2. La combinazione ha dimostrato una tollerabilità e un profilo di sicurezza favorevoli, coerenti con ribociclib e terapia endocrina. Risultati notevoli includono un tasso di beneficio clinico del 76% in tutti i pazienti e un tasso di risposta obiettiva del 27% nei pazienti con malattia misurabile.
Olema Oncology anunció resultados clínicos actualizados para el palazestrant combinado con ribociclib en el tratamiento del cáncer de mama avanzado o metastásico ER+/HER2-. Con un seguimiento mediano de 12 meses, el estudio mostró resultados prometedores con una supervivencia libre de progresión mediana (PFS) que aún no se ha alcanzado. La tasa de PFS a 6 meses fue del 73% en general, con el 81% en pacientes con mutación ESR1 y el 70% en pacientes de tipo salvaje ESR1.
El estudio de Fase 1b/2 incluyó a 62 pacientes, de los cuales 56 recibieron la dosis recomendada de Fase 2. La combinación demostró un perfil de tolerabilidad y seguridad favorable, consistente con ribociclib y terapia endocrina. Los resultados notables incluyen una tasa de beneficio clínico del 76% en todos los pacientes y una tasa de respuesta objetiva del 27% en pacientes con enfermedad medible.
올레마 온콜로지는 ER+/HER2- 진행성 또는 전이성 유방암 치료를 위한 리보시클립과 결합된 팔라제스트란트의 업데이트된 임상 결과를 발표했습니다. 12개월의 중간 추적 관찰을 통해 연구는 약 73%의 6개월 PFS 비율과 ESR1 변이 환자에서 81%, ESR1 야생형 환자에서 70%를 포함하여 아직 도달하지 않은 유망한 결과를 보여주었습니다.
1b/2상 연구에는 62명이 포함되었고 이 중 56명이 권장 2상 용량을 받았습니다. 이 조합은 리보시클립 및 내분비 요법과 일관된 유리한 내약성과 안전성 프로파일을 나타냈습니다. 주목할 만한 결과로는 모든 환자에서 76%의 임상 혜택율과 측정 가능한 질병이 있는 환자에서 27%의 객관적 반응률이 포함됩니다.
Olema Oncology a annoncé des résultats cliniques mis à jour pour le palazestrant associé au ribociclib dans le traitement du cancer du sein avancé ou métastatique ER+/HER2-. Avec un suit médian de 12 mois, l'étude a montré des résultats prometteurs avec une survie sans progression médiane (PFS) qui n'a pas encore été atteinte. Le taux de PFS à 6 mois était de 73% au total, avec 81% chez les patients présentant une mutation ESR1 et 70% chez les patients de type sauvage ESR1.
L'étude de phase 1b/2 a inclus 62 patients, dont 56 ont reçu la dose recommandée de phase 2. La combinaison a montré un profil de tolérabilité et de sécurité favorable, cohérent avec le ribociclib et la thérapie endocrinienne. Les résultats notables comprennent un taux de bénéfice clinique de 76% chez tous les patients et un taux de réponse objective de 27% chez les patients ayant une maladie mesurable.
Olema Oncology hat aktualisierte klinische Ergebnisse für Palazestrant in Kombination mit Ribociclib bei der Behandlung von ER+/HER2- fortgeschrittenem oder metastasierendem Brustkrebs bekannt gegeben. Bei einer 12-monatigen medianen Nachbeobachtungszeit zeigte die Studie vielversprechende Ergebnisse mit einer noch nicht erreichbaren medianen progressionsfreien Überlebenszeit (PFS). Die 6-Monats-PFS-Rate lag insgesamt bei 73%, bei ESR1-Mutationspatienten bei 81% und bei ESR1-Wildtyp-Patienten bei 70%.
Die Phase 1b/2-Studie umfasste 62 Patienten, von denen 56 die empfohlene Dosis für Phase 2 erhielten. Die Kombination zeigte ein günstiges Verträglichkeits- und Sicherheitsprofil, das mit Ribociclib zur endokrinen Therapie übereinstimmte. Bemerkenswerte Ergebnisse umfassen eine klinische Nutzenrate von 76% bei allen Patienten und eine objektive Ansprechrate von 27% bei Patienten mit messbarer Erkrankung.
- Median progression-free survival (PFS) not reached after 12 months of follow-up
- High 6-month PFS rate of 73% across all patients, with 81% in ESR1 mutation patients
- Strong clinical benefit rate of 76% across all patients
- 27% objective response rate in patients with measurable disease
- 48% of patients remain on treatment with longest duration of 18 months
- 74% of patients required prior treatment with CDK4/6 inhibitors
- Lower PFS rate (68%) in patients with prior CDK4/6 inhibitor treatment
Insights
The updated clinical results for palazestrant + ribociclib demonstrate significant promise in treating ER+/HER2- breast cancer. The 73% 6-month progression-free survival rate across all patients is particularly impressive, with even stronger results in ESR1-mutated cases at 81%. The fact that median PFS hasn't been reached after 12 months suggests durable treatment effects.
The clinical benefit rate of 76% across all patients and favorable tolerability profile indicate a potentially superior treatment option. Two confirmed complete responses and eight confirmed partial responses in 37 evaluable patients represent meaningful clinical activity. The drug combination's effectiveness in both ESR1 wild-type and mutant populations addresses a critical unmet need in treating resistance mechanisms.
These results are clinically meaningful for several reasons. First, the drug combination shows efficacy in patients previously treated with CDK4/6 inhibitors, with a 68% 6-month PFS rate in this population. This suggests potential utility in overcoming treatment resistance. Second, the safety profile aligns with existing ribociclib + endocrine therapy combinations, indicating no unexpected toxicity concerns.
The rapid response time noted by investigators is particularly significant, as traditional endocrine therapies typically require longer periods to show benefit. The 60% reduction in target lesion size among measurable disease patients further supports the combination's potent anti-tumor activity.
These clinical results significantly strengthen Olema's market position in the breast cancer treatment landscape. The data supports advancement to Phase 3 trials, potentially accelerating the path to commercialization. The drug's efficacy in both ESR1 mutant and wild-type populations expands the potential market opportunity.
With a
- Palazestrant, in combination with ribociclib, demonstrated promising clinical activity, a safety profile consistent with ribociclib and endocrine therapy, and favorable tolerability in patients with ER+/HER2- advanced or metastatic breast cancer
- With a median follow-up of 12 months, median progression-free survival (PFS) has not been reached
- 6-month PFS rate was
73% in all patients,81% in patients with ESR1 mutations,70% in ESR1 wild-type patients, and68% in patients with prior CDK4/6 inhibitor treatment; data continue to mature - Conference call today at 8:00 a.m. ET
SAN FRANCISCO, Dec. 10, 2024 (GLOBE NEWSWIRE) -- 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 breast cancer and beyond, today announced updated clinical results from the ongoing Phase 1b/2 study of palazestrant in combination with CDK4/6 inhibitor, ribociclib, in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced or metastatic breast cancer. Results as of September 25, 2024, will be presented in a poster session at the San Antonio Breast Cancer Symposium (SABCS 2024) being held December 10-13 at the Henry B. Gonzalez Convention Center in San Antonio, Texas. Updated results as of November 11, 2024, are detailed below.
“We believe these data, while still maturing, are compelling and highly differentiated, with robust clinical activity shown across both ESR1 wild-type and mutant patient populations after prior treatment with a CDK4/6 inhibitor in combination with endocrine therapy. Mutations in the ESR1 gene are one of the most common resistance mechanisms arising during current front-line standard of care treatment, leading to progression. Palazestrant has demonstrated its potential to work in combination with ribociclib by completely blocking estrogen receptor signaling and suppressing tumor growth to extend progression-free survival after prior progression on the current standard of care, regardless of ESR1 status,” said Sean P. Bohen, M.D., Ph.D., President and Chief Executive Officer of Olema Oncology. “These data provide the foundation to initiate OPERA-02, our planned pivotal Phase 3 trial of palazestrant in combination with ribociclib in front-line metastatic breast cancer next year. We look forward to sharing mature data from this combination in 2025 and continuing the development of palazestrant as we work to advance our goal of creating innovative therapies to improve the lives of breast cancer patients.”
Interim Results from the Phase 1b/2 Study of Palazestrant in Combination with Ribociclib
Enrollment
62 patients with advanced or metastatic ER+/HER2- breast cancer were treated with palazestrant (n=56 at the recommended Phase 2 dose (RP2D) of 120 mg once daily) plus ribociclib (600 mg once daily; three weeks on treatment followed by one week off treatment).
- The majority of participants (48 (
77% )) were 2/3+ line patients; 48 (77% ) patients received prior endocrine therapy for metastatic breast cancer, 46 (74% ) patients received prior treatment of endocrine therapy with CDK4/6 inhibitors (CDK4/6i), 12 (19% ) received two prior lines of treatment with CDK4/6i, and 11 (18% ) patients received chemotherapy for metastatic breast cancer. - 36 (
58% ) patients had visceral disease; 42 (68% ) patients had measurable disease at baseline. Of 60 patients whose circulating tumor DNA (ctDNA) was assessed,28% had activating mutations in ESR1 at baseline.
Efficacy
Palazestrant combined with ribociclib showed promising clinical activity including tumor responses, prolonged disease stabilization, and progression-free survival in patients with ESR1 wild-type and ESR1 activating mutations at baseline and in those previously treated with one or two lines of CDK4/6i. Efficacy data continue to mature; 30 (
- With a median follow-up of 12 months, the median PFS was not reached as of the data cutoff date. Across all patients, the 6-month PFS rate was
73% . In those who received prior treatment with a CDK4/6i plus an endocrine therapy, the 6-month PFS rate was68% . The 6-month PFS rate in ESR1 mutant patients was81% and in ESR1 wild-type patients it was70% . - In those who were clinical benefit rate (CBR)1-eligible, the CBR was
76% (37/49) in all patients,81% (13/16) in patients with ESR1 mutations, and74% (23/31) in ESR1 wild-type patients. In patients with prior CDK4/6i treatment, the CBR was71% (25/35),81% (12/16) in patients with ESR1 mutations, and65% (11/17) in ESR1 wild-type patients. - As of the data cutoff date, there were 11 responses (two confirmed complete responses, eight confirmed partial responses, and one unconfirmed partial response). Among 37 response-evaluable patients with measurable disease, the ORR was
27% (10/37).60% of the 37 had a reduction in target lesion size.
Safety and Tolerability
Across 62 treated patients, the combination of up to 120 mg of palazestrant with the approved dose for metastatic disease of 600 mg of ribociclib daily was well tolerated with no new safety signals or increase in toxicity. The overall safety profile was consistent with the established safety profile of ribociclib 600 mg plus an endocrine therapy.
- Treatment with palazestrant up to 120 mg combined with ribociclib (600 mg) was well tolerated with no dose-limiting toxicities.
- 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.
Pharmacokinetics
Palazestrant did not affect ribociclib 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.
Conclusions
Findings from this study support the advancement of palazestrant in combination with ribociclib into clinical development for the first-line treatment of ER+/HER2- advanced or metastatic breast cancer.
“Palazestrant is not an endocrine therapy where you need to wait six months to see a patient derive benefit. We have seen impressive responses quickly and a significant reduction of disease burden. The patients I have seen feel much better than they have on other treatments available in the armamentarium today,” said Virginia Borges, M.D., Professor, Medicine-Medical Oncology at the University of Colorado, and Principal Investigator for the palazestrant plus ribociclib combination study. “The findings presented at SABCS show that the combination of palazestrant and ribociclib is well-tolerated with meaningful preliminary efficacy that I believe has the potential to outperform the current standard of care and change how metastatic breast cancer is treated. I look forward to the continued development of palazestrant.”
A copy of the poster presented at SABCS reflecting a September 25, 2024 data cutoff date will be made available on the Publications page of Olema’s website in alignment with the Symposium’s embargo policy.
1CBR is the proportion of patients who remained on treatment through at least 24 weeks with a confirmed complete response or partial response, or stable disease.
Conference Call Information
Olema will hold a conference call to discuss these results today with the investment community at 8:00 a.m. ET (7:00 a.m. CT). Register to join the webcast by visiting the Events and Presentations page on the Investors section of Olema’s website.
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 preclinical studies, palazestrant completely blocks ER-driven transcriptional activity in both ESR1 wild-type and mutant forms of breast cancer. In Olema’s ongoing clinical trials for advanced or metastatic ER+/HER2- breast cancer, palazestrant has demonstrated anti-tumor activity along with attractive pharmacokinetics and exposure, favorable tolerability, 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 on OPERA-01, 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 patients living with breast cancer and beyond. Olema is advancing a pipeline of novel therapies by leveraging our deep understanding of endocrine-driven cancers, nuclear receptors, and mechanisms of acquired resistance. Our lead product candidate, palazestrant (OP-1250), is a proprietary, orally available complete estrogen receptor (ER) antagonist (CERAN) and a selective ER degrader (SERD), currently in a Phase 3 clinical trial called OPERA-01. In addition, 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,” “believe,” “could,” “expect,” “goal,” “may,” “potential,” “upcoming,” “will,” 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 and the development of palazestrant, in each case, including in combination with other drugs, the potential of palazestrant to work in combination with ribociclib to suppress tumor growth or extend progression-free survival, the initiation and timing of clinical trials, and Olema’s potential to transform the endocrine therapy standard of care treatments for patients 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 September 30, 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.
Media and Investor Relations Contact
Courtney O’Konek
Vice President, Corporate Communications
Olema Oncology
media@olema.com
FAQ
What are the latest clinical results for Olema's (OLMA) palazestrant and ribociclib combination?
What is the safety profile of palazestrant in Olema's (OLMA) Phase 1b/2 study?
What is the response rate in Olema's (OLMA) palazestrant breast cancer trial?
