On December 10, 2024 Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical stage biopharmaceutical company developing targeted protein modulation drugs designed to treat patients with cancer and inflammatory diseases, reported new positive clinical data from patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) treated in the Phase 1a/1b clinical trial of its Bruton’s tyrosine kinase (BTK) degrader NX-5948 (Press release, Nurix Therapeutics, DEC 10, 2024, View Source [SID1234648999]). These data were presented by Nirav N. Shah, M.D., M.S.H.P., Associate Professor of Medicine, Division of Hematology and Oncology, at the Medical College of Wisconsin, and a clinical investigator on the trial, in an oral session at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition being held December 7-10, 2024, in San Diego, CA. In addition, Nurix and its collaborators presented new preclinical data for NX-5948 and its BTK and IKZF1/3 degrader NX-2127 in separate poster and oral presentations at the ASH (Free ASH Whitepaper) Annual Meeting.

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"We are excited to report our latest results based on enrollment of sixty relapsed/refractory CLL/SLL patients, almost double the number of patients in our previous mid-year 2024 update. With a greater number of patients and longer duration of treatment, we are highly encouraged to see a deepening of therapeutic responses over time while maintaining a favorable safety profile," said Paula G. O’Connor, M.D., chief medical officer of Nurix. "These positive results are particularly impressive given the inclusion of patients with a high incidence of baseline genetic mutations in BTK, PLCG2, and TP53, and challenging clinical factors, such as central nervous system involvement, which are associated with poor prognosis. We continue to enroll patients in the United States, the United Kingdom, and Europe in the Phase 1b portion of the trial and are on track to initiate pivotal trials of NX-5948 in 2025."

NX-5948 Phase 1a/1b clinical update
As of the October 10, 2024 data cut, sixty (60) patients with relapsed or refractory CLL/SLL were enrolled. This cohort of CLL/SLL patients was a heavily pretreated population that had received a median of four prior lines of therapy (range = 1-12) including prior covalent BTK inhibitors (98.3%), prior BCL2 inhibitors (83.3%), and prior non-covalent BTK inhibitors (28.3%). At baseline, a large number of patients had mutations associated with BTK inhibitor resistance, including mutations in BTK (38.6%) and PLC2G (12.3%). Poor prognostic features were common, including TP53 mutations (40.4%), and five patients (8.3%) had central nervous system (CNS) involvement.

The data presented at the ASH (Free ASH Whitepaper) Annual Meeting include safety findings for all patients in the NX-5948 Phase 1a/1b dose escalation and expansion cohorts (n=125), including those with CLL/SLL and those with non-Hodgin’s lymphoma (NHL). Patients were treated with NX-5948 at starting doses ranging from 50 mg to 600 mg once daily by oral administration, and intra-patient dose escalation was permitted per protocol. NX-5948 was well tolerated across all doses evaluated, and safety findings in the CLL/SLL cohort were consistent with the overall population as well as previous safety analyses. Among the CLL/SLL patients, the most common treatment emergent adverse events were purpura/contusion (36.7%, all grade 1 or 2), fatigue (26.7%, all grade 1 or 2), petechiae (26.7%, all grade 1 or 2), neutropenia (23.3%, 18.3% grade 3 or higher), and rash (23.3%, 1.7% grade 3 or higher). Importantly, across the entire population, there was only one case of grade 1 atrial fibrillation in a patient with pre-existing atrial fibrillation.

Among the efficacy evaluable patients with CLL/SLL (n=49), NX-5948 treatment resulted in a robust objective response rate (ORR) of 75.5% across all doses tested, with the majority of responses occurring at the first assessment (Week 8). With longer time on treatment, the ORR increased to 84.2% based on an exploratory efficacy analysis of patients who had at least two response assessments (Week 16). Responses were observed across all populations regardless of prior treatment, baseline mutations, high-risk molecular features, or CNS involvement. This includes patients with baseline BTK mutations associated with treatment resistance to both covalent and non-covalent BTK inhibitors. Robust BTK degradation was observed in all patients, including those with baseline BTK mutations.

Responses were durable with the median duration of response not reached. Thirteen patients had duration of response greater than six months, and five patients remain on treatment and in response beyond one year of treatment.

Additional preclinical data presentations
Nurix and its collaborators presented new preclinical data for NX-5948 in an animal model of primary CNS lymphoma (PCNSL) and assessed the impact of NX-2127 on T cell function.

Preclinical data were presented demonstrating the positive effects of brain-penetrant NX-5948 treatment on survival in a patient-derived xenograft model of primary central nervous system lymphoma (PCNSL) in a poster titled: BTK Degradation As a Novel Therapeutic Strategy in Relapsed CNS Lymphoma: Proof of Concept Studies in Intracranial Patient-Derived, Rodent Models. The data demonstrate that daily oral administration of NX-5948 drives potent degradation of BTK, inhibition of extracellular signal-regulated kinase (ERK) and prolonged survival in the setting of CNS lymphoma. In addition, transcriptional changes associated with enhanced tumor antigen presentation and reduced tumor progression were observed in NX-5948 treated animals. Notably, oral administration of ibrutinib resulted in similar level of ERK inhibition but did not lead to prolonged survival or the same pattern of transcriptional changes in the model, suggesting that BTK degradation by NX-5948 exhibits differential biology relative to BTK inhibition by ibrutinib, a result that may be associated with the elimination of BTK’s scaffolding function by NX-5948.

In addition, preclinical results were presented demonstrating that although both NX-2127 and NX-5948 effectively degrade BTK in primary CLL cells while preserving T-cell activation and survival in vitro, NX-2127 demonstrates unique immunomodulatory activity. These data were the subject of an oral presentation titled: NX-2127 and NX-5948, Two Clinical Stage Cereblon-Recruiting BTK Degraders, Facilitate T Cell Functionality in Chronic Lymphocytic Leukemia. Specifically, the data demonstrate distinct immunomodulatory effects in NX-2127 treated CLL cells, including upregulation of CD38, an interferon (IFN)-response gene, bolstering the immune response, promotion of T cell differentiation towards a TH1 phenotype, enhancing anti-tumor immunity, reduction in Treg differentiation, which supports a shift toward a less immunosuppressive microenvironment and enhancement of immunological synapse formation, and T cell-mediated cytotoxicity. In addition, RNA sequencing revealed unique patterns of gene expression in NX-2127-treated CLL cells, distinguishing responders from non-responders and further demonstrating its distinctive T cell modulatory effects.

About NX-5948: NX-5948 is an investigational, orally bioavailable degrader of BTK that is currently being evaluated in a Phase 1a/b clinical trial in adults with relapsed or refractory B-cell malignancies. Additional information on the Phase 1a/b clinical trial can be accessed at www.clinicaltrials.gov (NCT05131022).

About NX-2127: NX-2127 is an investigational, orally bioavailable degrader of BTK and cereblon neosubstrates Ikaros (IKZF1) and Aiolos (IKZF3). NX-2127 is currently being evaluated in a Phase 1a/b clinical trial in adults with relapsed or refractory B-cell malignancies. Additional information on the ongoing clinical trial can be accessed at www.clinicaltrials.gov (NCT04830137).

On December 10, 2024 Incyte (Nasdaq:INCY) reported additional results from the pivotal Phase 3 inMIND trial evaluating treatment with tafasitamab (Monjuvi), a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody, in combination with lenalidomide and rituximab compared with placebo plus lenalidomide and rituximab in patients with relapsed or refractory follicular lymphoma (FL) (Press release, Incyte, DEC 10, 2024, View Source [SID1234649015]). These data are featured today in the Late-breaking Session (LBA-1) at the 2024 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego.

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The late-breaking results, which build on previously announced topline data, show that the study met its primary endpoint by demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) by investigator assessment in 548 patients with FL. Patients treated with tafasitamab achieved a median PFS by investigator assessment of 22.4 months compared to 13.9 months in the control arm (Hazard Ratio [HR]: 0.43; 95% Confidence Interval [CI] (0.32—0.58); P<0.0001), representing a 57% reduction in risk of progression, relapse, or death. The PFS assessed by an Independent Review Committee (IRC) was consistent with investigator-based results, with a HR of 0.41 (95% CI 0.29, 0.56, P<0.0001). Median PFS by IRC was not reached in the tafasitamab group versus 16.0 months in the control arm, [95% CI (19.3-NE) and (13.9, 21.1), respectively; P<0.0001]. The PFS benefit was consistent across all patient subgroups regardless of the number of previous lines of therapy.

"In the Phase 3 inMIND trial, tafasitamab demonstrated impressive efficacy and safety for treating certain patients with follicular lymphoma, the most common type of B-cell non-Hodgkin lymphoma," said Steven Stein, M.D., Chief Medical Officer, Incyte. "These data, the first to evaluate the novel approach of combining CD19 and CD20 immunotherapies, show the potential of tafasitamab in combination with lenalidomide and rituximab to become a new standard of care for these patients. We look forward to working with regulatory authorities to potentially bring this treatment forward to patients with FL."

The trial also showed improvement across secondary endpoints, including:

Complete response (CR), overall response rate (ORR) and duration of response (DOR) each showed improvement in the tafasitamab group versus the control arm (CR of 49.4% vs. 39.8% [95% CI (43.1, 55.8) and (33.7, 46.1), respectively; OR=1.5, P=0.0286); (ORR of 83.5% vs. 72.4% [95% CI (78.6, 87.7) and (66.7, 77.6), respectively]); (DOR of 21.2 months vs. 13.6 months [95% CI (19.5—NE) and (12.4—18.6), respectively]).
Median overall survival (OS) was not reached in either group, but a positive trend was observed with the tafasitamab group versus the control arm (HR=0.59 [95% CI (0.31, 1.13)]).
Additionally, median time to next treatment (TTNT) was not reached in the tafasitamab group and was 28.8 months in the control arm (HR [95% CI], 0.45 [0.31, 0.64], nominal P<0.0001).

Tafasitamab was generally well-tolerated, and safety was consistent with other CD19 and immunotherapy combination regimens. The most common treatment-emergent adverse events (TEAEs) in the tafasitamab and immunotherapy combination group were neutropenia (48.5%), diarrhea (37.6%), COVID-19 (31.4%) and constipation (29.2%).

"Patients with follicular lymphoma have a high risk of relapse, yet there are limited treatment options in the relapsed and refractory setting," said Dr. Laurie Sehn, British Columbia Cancer Centre for Lymphoid Cancer. "The goal of therapy is primarily to prolong remission, while maintaining quality of life. The inMIND trial demonstrated a meaningful improvement in disease control with the addition of the anti-CD19 monoclonal antibody tafasitamab to lenalidomide and rituximab, providing patients with a new, well tolerated, immunotherapy combination."

About inMIND
A global, double-blind, randomized, controlled Phase 3 study, inMIND (NCT04680052) evaluated the clinical benefit of tafasitamab and lenalidomide as an add-on to rituximab compared with lenalidomide alone as an add-on to rituximab in patients with relapsed or refractory follicular lymphoma (FL) Grade 1 to 3a or relapsed or refractory nodal, splenic or extranodal marginal zone lymphoma (MZL). The study enrolled a total of 654 adults (age ≥18 years).

The primary endpoint of the study is progression-free survival (PFS) by investigator assessment in the FL population, and the key secondary endpoints are PFS in the overall population as well as positron emission tomography complete response (PET-CR) and overall survival (OS) in the FL population.

For more information about the study, please visit View Source

About Tafasitamab (Monjuvi)
Tafasitamab (Monjuvi) is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Antibody-Dependent Cellular Phagocytosis (ADCP). MorphoSys and Incyte entered into: (a) in January 2020, a collaboration and licensing agreement to develop and commercialize tafasitamab globally; and (b) in February 2024, an agreement whereby Incyte obtained exclusive rights to develop and commercialize tafasitamab globally.

In the United States, Monjuvi (tafasitamab-cxix) received accelerated approval by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). In Europe, Minjuvi (tafasitamab) received conditional Marketing Authorization from the European Medicines Agency in combination with lenalidomide, followed by Minjuvi monotherapy, for the treatment of adult patients with relapsed or refractory DLBCL who are not eligible for ASCT.

XmAb is a registered trademark of Xencor, Inc.

Monjuvi, Minjuvi, the Minjuvi and Monjuvi logos and the "triangle" design are registered trademarks of Incyte.

IMPORTANT SAFETY INFORMATION

What are the possible side effects of MONJUVI?
MONJUVI may cause serious side effects, including:

Infusion reactions. Your healthcare provider will monitor you for infusion reactions during your infusion of MONJUVI. Tell your healthcare provider right away if you get fever, chills, flushing, headache, or shortness of breath during an infusion of MONJUVI.
Low blood cell counts (platelets, red blood cells, and white blood cells). Low blood cell counts are common with MONJUVI, but can also be serious or severe. Your healthcare provider will monitor your blood counts during treatment with MONJUVI. Tell your healthcare provider right away if you get a fever of 100.4°F (38°C) or above, or any bruising or bleeding.
Infections. Serious infections, including infections that can cause death, have happened in people during treatment with MONJUVI and after the last dose. Tell your healthcare provider right away if you get a fever of 100.4°F (38°C) or above, or develop any signs and symptoms of an infection.
The most common side effects of MONJUVI include:

Feeling tired or weak
Diarrhea
Cough
Fever
Swelling of lower legs or hands
Respiratory tract infection
Decreased appetite
These are not all the possible side effects of MONJUVI. Your healthcare provider will give you medicines before each infusion to decrease your chance of infusion reactions. If you do not have any reactions, your healthcare provider may decide that you do not need these medicines with later infusions. Your healthcare provider may need to delay or completely stop treatment with MONJUVI if you have severe side effects.

Before you receive MONJUVI, tell your healthcare provider about all of your medical conditions, including if you:

Have an active infection or have had one recently.
Are pregnant or plan to become pregnant. MONJUVI may harm your unborn baby. You should not become pregnant during treatment with MONJUVI. Do not receive treatment with MONJUVI in combination with lenalidomide if you are pregnant because lenalidomide can cause birth defects and death of your unborn baby.
You should use an effective method of birth control (contraception) during treatment and for at least 3 months after your final dose of MONJUVI.
Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with MONJUVI.
Are breastfeeding or plan to breastfeed. It is not known if MONJUVI passes into your breastmilk. Do not breastfeed during treatment for at least 3 months after your last dose of MONJUVI.
You should also read the lenalidomide Medication Guide for important information about pregnancy, contraception, and blood and sperm donation.

Tell your healthcare provider about all the medications you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Incyte Medical Information at 1-855-463-3463.

Please see the full Prescribing Information for Monjuvi, including Patient Information, for additional Important Safety Information.

On December 10, 2024 ImmunityBio, Inc. (NASDAQ: IBRX), a leading immunotherapy company, reported that it intends to offer and sell, subject to market and other conditions, shares of its common stock in an underwritten public offering (Press release, ImmunityBio, DEC 10, 2024, View Source [SID1234648984]). In addition, ImmunityBio expects to grant the underwriters a 30-day option to purchase up to an additional 15% of the shares of common stock offered in the offering at the public offering price, less underwriting discounts and commissions. ImmunityBio currently intends to use the net proceeds from this offering to progress its continued commercialization of ANKTIVA for treatment of BCG-unresponsive non-muscle invasive bladder cancer ("NMIBC") with carcinoma in situ ("CIS") with or without papillary tumors, to fund its trials in BCG-naïve NMIBC and non-small cell lung cancer ("NSCLC"), toward further research and development, for working capital needs, and for other general corporate purposes. All of the shares are being offered by ImmunityBio. There can be no assurance as to whether or when the offering may be completed, or the actual size or terms of the offering.

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Jefferies and Piper Sandler are acting as joint book-running managers and representatives of the underwriters for the offering. BTIG and H.C. Wainwright & Co. are acting as co-lead managers for the offering.

A shelf registration statement on Form S-3ASR relating to the common stock offered in the public offering described above was filed with the Securities and Exchange Commission ("SEC") on April 17, 2024 and became automatically effective on April 17, 2024. The proposed offering is being made only by means of a prospectus supplement and accompanying prospectus that form a part of the registration statement. A preliminary prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. Copies of the preliminary prospectus supplement and accompanying prospectus relating to the offering, when available, may also be obtained from Jefferies LLC, by mail at Attn: Equity Syndicate Prospectus Department, 520 Madison Avenue, New York, New York 10022, by telephone at (877) 821-7388 or by email at [email protected], or Piper Sandler & Co. by mail at Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, MN 55402 or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy the securities being offered, nor shall there be any sale of the securities being offered in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction. The offering may be made only by means of a prospectus supplement and accompanying prospectus.

On December 10, 2024 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, reported 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 (Press release, Olema Oncology, DEC 10, 2024, View Source [SID1234649000]). 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.

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"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 (48%) patients remain on treatment, and the longest duration on treatment is approximately 18 months (79 weeks) and was ongoing as of the data cutoff date of November 11, 2024.

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 was 68%. The 6-month PFS rate in ESR1 mutant patients was 81% and in ESR1 wild-type patients it was 70%.
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, and 74% (23/31) in ESR1 wild-type patients. In patients with prior CDK4/6i treatment, the CBR was 71% (25/35), 81% (13/16) in patients with ESR1 mutations, and 65% (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.

On December 10, 2024 BostonGene, a leading provider of AI-driven molecular and immune profiling solutions, reported that three abstracts have been accepted for poster presentations at the 2024 San Antonio Breast Cancer Symposium (SABCS), to take place December 10 – 13, 2024, at the Henry B. Gonzalez Convention Center in San Antonio, Texas (Press release, BostonGene, DEC 10, 2024, View Source [SID1234649016]). BostonGene will also exhibit at booth 1317.

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"We’re excited to present our research at the 2024 SABCS, underscoring BostonGene’s commitment to leveraging molecular profiling as a transformative tool in breast cancer treatment," said Nathan Fowler, MD, Chief Medical Officer at BostonGene. "Our findings in transcriptomic classification aim to pave the way for more effective treatment pathways, establishing new benchmarks for precision oncology."

Details about the abstracts selected for presentation are below:

Abstract number: 1760
Title: Evaluating the Correlation Between FISH and NGS in Assessing ERBB2 Alterations in Breast Cancer
Date & time: Wednesday, December 11 | 12:00 PM – 2:00 PM
Presenter: Nikita Kotlov, BostonGene

This comparative analysis demonstrated the utility of NGS in evaluating ERBB2 (HER2) status in breast cancer compared to the gold standard, fluorescence in situ hybridization (FISH). NGS detected potentially clinically relevant ERBB2 mutations in non-amplified samples. With enhanced resolution, NGS also revealed heterogeneity among ERBB2 (HER2) amplifications in breast cancer. Identifying these nuanced genomic and transcriptomic alterations yields valuable insights for designing personalized treatment strategies for breast cancer patients.

Abstract number: 2476
Title: Comprehensive Analysis of ADC Target Expression in Invasive Lobular Carcinoma
Date & time: Wednesday, December 11 | 12:00 PM – 2:00 PM
Presenter: Jason Mouabbi, MD, The University of Texas MD Anderson Cancer Center

RNA-seq was applied to examine 82 cell surface proteins as potential antibody-drug conjugate (ADC) targets in invasive lobular carcinoma (ILC). Distinct expression landscapes of the prospective ADC targets were present across different ILC subtypes. These findings underscore the need to account for varied ADC target expression landscapes across ILC subtypes for optimal efficacy and safety of ADC-based treatments.

Research done in collaboration with MD Anderson Cancer Center

Abstract number: 1521
Title: Levels of Circulating Tumor DNA as a Predictive Marker for Early Switch in Treatment for Patients with Metastatic Breast Cancer: A Phase 2 Randomized, Open-Label Study
Date & time: Thursday, December 12 | 5:30 PM – 7:00 PM
Presenter: Frances Valdes, MD, University of Miami

This phase 2 randomized, open-label study compares patients with metastatic breast cancer receiving a CDK4/6 inhibitor combined with either an aromatase inhibitor or fulvestrant as first-line therapy. BostonGene’s liquid biopsy test was incorporated to validate the clinical utility of serial circulating tumor (ctDNA) for patient monitoring. Capable of detecting molecular progression before clinical manifestation, levels of ctDNA were predictive for early switch in treatment in metastatic breast cancer patients. While analysis and patient monitoring are ongoing, this study has yielded clinically relevant genomic findings that may shed light on strategies to extend the duration of disease control and prolong patient survival.

Research done in collaboration with the University of Miami