On December 5, 2023 SystImmune, Inc (SystImmune), a clinical-stage biopharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) authorized the company to proceed with the planned clinical study of the HER2-specific HIRE platform ADC, BL-M07D1, in the Investigational New Drug (IND) application on November 28, 2023 (Press release, SystImmune, DEC 5, 2023, View Source [SID1234638171]). This milestone paves the way for the multicenter Phase 1 study evaluating the safety, tolerability, pharmacokinetic profile, and initial efficacy of BL-M07D1 in subjects with metastatic or unresectable HER2 expressing cancers in the United States.

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Dr. Yi Zhu, Chief Executive Officer of SystImmune, remarked, "The FDA’s approval of our IND application for BL-M07D1 underscores our commitment to advancing innovative therapies in the field of oncology with our HIRE platform of ADCs. We look forward to collaborating with our clinical partners, trial treatment centers, and global regulatory agencies to contribute meaningfully to the ongoing evolution of cancer treatment."

The clearance of this IND application marks a significant milestone for SystImmune as the company continues to advance its pipeline of therapeutic candidates into global clinical development.

Updated Clinical Trial Results

New results from the ongoing study with the EGFRxHER3 bi-specific HIRE platform ADC, BL-B01D1, in patients with breast cancer treated in the trial registered as NCT05470348, are presented for the first time. Preliminary results demonstrated overall response rates of 44.7%, 31.4% and 39.1% and disease control rates of 91.4%, 94.7% and 87% in an analysis of 38, 35 and 23 pretreated patients with HER2-/HR+, TNBC and HER 2+ patients with breast cancer respectively. No interstitial lung disease (ILD) was observed in 127 patients treated with at least one dose. For more information visit poster: PS08-07 2023 San Antonio Breast Cancer conference.

Updated analysis from an ongoing phase 1 study of the HIRE platform HER2-specific ADC, BL-M07D1 in the trial registered as NCT05461768, continues to demonstrate impressive results in patients with breast cancer. Reported are response rate of 80%, confirmed responses over 60%, and disease control rate of 100% in 50 patients with HER2+ metastatic breast cancer. Prior treatment with HER2 ADCs did not prevent responses to BL-M07D1, as 18 subjects who had received prior ADC therapies showed similar overall response. Preliminary results from the same study demonstrated an overall response rate of 50%, confirmed responses in 28.9% and disease control rate of 86% in an analysis of 38 heavily pretreated patients with HER2 low-expressing metastatic breast cancer. Only 1 patient experienced ILD which was grade 2, in the 130 patients treated. For more information visit poster: PO2-04-03 2023 San Antonio Breast Cancer conference.

Dr. Martin S. Olivo, the Chief Medical Officer at SystImmune, reports the preliminary findings showcased in these two studies, underscoring their backing of the promising activity seen in the HIRE platform. Dr. Olivo emphasized the significance of the FDA clearance for the IND application of BL-M07D1, expressing optimism. "As the clinical development of BL-M07D1 and BL-B01D1 progress, we’re closer to assessing our potential to offer therapeutic pathways for patients diagnosed with breast cancer."

About BL-B01D1

BL-B01D1 is a first-in-class bispecific antibody-drug conjugate (ADC) developed by SystImmune, targeting both EGFR and HER3, proteins that are highly expressed in most epithelial tumors. The tetravalent BL-B01D1 possesses two binding domains blocking each Growth Factor Receptor, which both drive cancer cell proliferation and survival. Inheriting the SI-B001 mechanisms of action, BL-B01D1 effectively blocks EGFR and HER3 signals to cancer cells, thereby reducing proliferation and survival signals. Upon antibody-mediated internalization, BL-B01D1 is trafficked to cancer cell lysosomes and liberates its therapeutic payload that induced genotoxic stress activating pathways leading to cancer cell death.

The two targets of BL-B01D1 are broadly expressed in epithelial tumors, including NSCLC, Head and Neck Squamous Cell Carcinoma, Nasopharyngeal carcinoma, Gastrointestinal tumors, Gynecological tumors, and others. The therapeutic conjugated toxin of BL-B01D1 comprises SystImmune’s Ex-0115 linker-payload platform, a proprietary Topo1 inhibitor conjugated to the bi-specific antibody by a stable, cleavable linker. Each BL-B01D1 carries 7-8 units of SystImmune’s proprietary ED-04 toxin.

About BL-M07D1

BL-M07D1 is a HER2 specific antibody-drug conjugate (ADC) developed by SystImmune, targeting cancers that express HER2. The trastuzumab-based BL-M07D1 possesses two binding domains specific for the commonly overexpressed cancer growth factor receptor HER2, which drive cancer cell proliferation and survival. BL-M07D1 binding to HER2 leads to its internalization by cancer cells. Upon antibody-mediated internalization, BL-M07D1 is trafficked to cancer cell lysosomes and liberates its therapeutic payload that induced genotoxic stress activating pathways leading to cancer cell death.

The target of BL-M07D1, HER2, is highly expressed in solid tumors, including breast cancer, gastric cancer, endometrial cancer, cervical cancer, ovarian cancer, urothelial cancer, biliary tract cancer and others. The therapeutic conjugated toxin of BL-M07D1 comprises SystImmune’s Ex-0115 linker-payload platform, a proprietary Topo1 inhibitor conjugated to the antibody by a stable, cleavable linker. Each BL-M07D1 carries 7-8 units of SystImmune’s proprietary ED-04 toxin.

Clinical studies conducted thus far have demonstrated compelling results for BL-M07D1. In 107 subjects with HER2+ Breast cancer and other HER2+ cancer BL-M07D1 exhibited promising preliminary antitumor activity in patients with both breast cancer and non-small cell lung cancer. The maximum tolerated dose for BL-M07D1 was not reached. The observed toxicities were predominantly hematologic. These findings were recently presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in October 2023, and the abstract of the clinical study can be accessed at the following link: BL-M07D1 ESMO (Free ESMO Whitepaper) Abstract. These results indicate that further investigations and clinical trials are warranted to fully assess the efficacy and safety profile of BL-M07D1 in a larger and more diverse patient population.

On December 5, 2023 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, reported the interim analysis results of ORIENT-16, the Phase 3 study evaluating sintilimab in combination with chemotherapy compared to chemotherapy for the first-line treatment of advanced or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma was published in The Journal of the American Medical Association (JAMA, IF=120.7) (Press release, Innovent Biologics, DEC 5, 2023, View Source [SID1234638170]). ORIENT-16 the first immunotherapy Phase 3 study published in JAMA for the first-line treatment of gastric cancer, as well as the first immunotherapy Phase 3 in Chinese patients for the first-line treatment of gastric cancer.

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Gastric cancer is one of the most common malignant tumor types globally and nearly half of all cases are diagnosed in China[i]. Advanced gastric cancer generally has very poor prognosis with high unmet medical need. ORIENT-16 demonstrated that sintilimab plus chemotherapy significantly prolongs overall survival in the first line treatment for overall population of gastric cancer. Based on the results of ORIENT-16, sintilimab is recommended by the Chinese Society of Clinical Oncology (CSCO) guidelines for the first-line treatment of gastric cancer. It is also the first and only PD-1 inhibitor included in national reimbursement drug list (NRDL) for the first-line treatment of gastric cancer.

ORIENT-16 has met its primary endpoint at the prespecified interim analysis. Sintilimab in combination with chemotherapy demonstrated superior and clinical meaningful overall survival (OS) benefit, compared with placebo plus chemotherapy in all randomized patients as well as patients with CPS ≥5 . Detailed interim analysis results were published in JAMA.

Interim analysis (cut-off date June 20, 2021, median follow-up 18.8 month) showed that, sintilimab in combination with chemotherapy significantly reduced the risk of death in all randomized patients (HR 0.77, 95%CI 0.63-0.94, p=0.009) and in patients with CPS ≥5 (HR 0.66, 95%CI 0.50-0.86, p=0.002) , successfully reached the prespecified superiority criteria. Median overall survival (mOS) has been prolonged by 2.9months (mOS 15.2mo vs. 12.3mo) in all randomized patients, and 5.5 months (mOS 18.4mo vs. 12.9mo) in patients with CPS ≥5, respectively. In addition, OS benefits were consistent in all prespecified subgroups. The safety profile of sintilimab in this study was consistent with that observed in previously reported studies of sintilimab, and no additional safety signals were identified for the combination of sintilimab and chemotherapy in GC patients.
Furthermore, prespecified final analysis results of ORIENT-16 has been published at the AACR (Free AACR Whitepaper) (American Association for Cancer Research) Annual Meeting. Final analysis (with additional 15-month follow-up) indicated that OS benefits of sintilimab plus chemotherapy have become more evident in overall population and in patients with CPS ≥5 compared with that of interim analysis, further confirming sintilimab plus chemotherapy as a standard of care of 1L treatment for G/GEJ adenocarcinoma.

Final analysis (cut-off date September 2, 2022, median follow-up 33.9 mo) showed that, sintilimab in combination with chemotherapy significantly reduced the risk of death in all randomized patients (HR 0.68, 95% CI: 0.57-0.81; P<0.0001) as well as in patients with CPS ≥5 (HR 0.59, 95% CI: 0.47-0.74; P<0.0001) . Median overall survival (mOS) has been prolonged by 2.9months (mOS 15.2mo vs. 12.3mo) in all randomized patients and by 6.3 months (mOS 19.2mo vs. 12.9mo) in patients with CPS ≥5, respectively. OS benefits were consistent in all prespecified subgroup analyses. The overall safety profile of final analysis was consistent with that observed in previously reported interim analysis, and no additional safety signals were identified with additional 15-month follow-up.
Based on the study results of ORIENT-16, sintilimab in combination with chemotherapy was approved by the National Medical Products Administration (NMPA) of China as first-line treatment for G/GEJ in June 2022, and was included in the national reimbursement drug list (NRDL), becoming the first and only immunotherapy for gastric cancer covered by NRDL in China.

The principal investigator of the ORIENT-16 study, Prof. Jianming Xu from the Fifth Medical Center of People’s Liberation Army General Hospital, stated, "ORIENT-16 is the first phase 3 trial in China to demonstrate a significant overall survival benefit in patients with advanced G/GEJ cancer treated with anti-PD-1 antibody plus chemotherapy in first line setting. The study has met its primary endpoint in the prespecified interim result analysis, and its final analysis demonstrated the OS benefit of sintilimab plus chemotherapy in overall population and in patients with CPS ≥5 compared with chemotherapy alone. ORIENT-16 confirms sintilimab plus chemotherapy as an important new treatment option and a standard of care of first line treatment for G/GEJ adenocarcinoma."

Dr. Zhou Hui, Senior Vice President of Innovent, stated, "The treatment options for advanced G/GEJ cancer are relatively limited and the ORIENT-16 study aimed to address this urgent unmet medical need. ORIENT-16 is the first randomized controlled Phase 3 study in China to demonstrate that PD-1 in combination with chemotherapy significantly prolongs overall survival in overall population of first line treatment for G/GEJ adenocarcinoma. The publication in JAMA further confirms its huge clinical value of the ORIENT-16 study. We are grateful for all the contributions made by every investigator and patient in this study. Up until now, sintilimab is the only PD-1 inhibitor in China approved and included in NRDL for the first-line treatment of five major types of cancer – non-squamous non-small cell lung cancer, squamous non-small cell lung cancer, hepatocellular carcinoma, esophageal squamous cell carcinoma, and gastric cancer. Sintilimab is also the first and only immunotherapy for gastric cancer covered by NRDL. We hope this novel immunotherapy to benefit a wider group of cancer patients."

About the ORIENT-16 Study

ORIENT-16 is a randomized, double-blind, multicenter Phase 3 clinical study evaluating sintilimab in combination with chemotherapy, compared to placebo in combination with chemotherapy, for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (ClinicalTrials.gov, NCT03745170). The primary endpoint was overall survival, in all randomized and in PD-L1 positive patients.

About Gastric Cancer

Gastric cancer is one of the most common malignant tumor types worldwide. According to GLOBOCAN estimates, there were approximately one million new cases and 769,000 new deaths of gastric cancer in 2020, making it the fifth most common cancer and third leading cause of cancer death globallyi[ii]. About half of all gastric cancer cases occurred in East Asia, mainly in Chinai. The first-line treatment of advanced gastric cancer remains limited. Currently, the 5-year survival rate of advanced or metastatic gastric cancer ranges from 5 to 20 percent. The median survival was about 1 year for patients who received chemotherapy only[iii][iv].

About Sintilimab

Sintilimab, marketed as TYVYT (sintilimab injection) in China, is a PD-1 immunoglobulin G4 monoclonal antibody co-developed by Innovent and Eli Lilly and Company. Sintilimab is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells[v]. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab has been approved for seven indications and included in the National Reimbursement Drug List (NRDL) for six indications. The updated NRDL reimbursement scope of TYVYT (sintilimab injection) include:

For the treatment of unresectable locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma;
For the treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma;
For the treatment of unresectable locally advanced or metastatic non-squamous non-small cell lung cancer lacking EGFR or ALK driver gene mutations;
For the treatment of unresectable locally advanced or metastatic squamous non-small cell lung cancer;
For the treatment of unresectable or metastatic hepatocellular carcinoma with no prior systematic treatment;
For the treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy.
Additionally, sintilimab has been approved in combination with bevacizumab and chemotherapy (pemetrexed and cisplatin) for the treatment of patients with EGFR-mutated nsqNSCLC who progressed after EGFR-TKI therapy.

Besides, two clinical studies of sintilimab have met their primary endpoints:

Phase 2 study of sintilimab monotherapy as second-line treatment of esophageal squamous cell carcinoma;
Phase 3 study of sintilimab monotherapy as second-line treatment for squamous NSCLC with disease progression following platinum-based chemotherapy.
Statement: Innovent does not recommend the use of any unapproved drugs/indications.

On December 5, 2023 Allarity Therapeutics, Inc. ("Allarity" or the "Company") (Nasdaq: ALLR), a clinical-stage pharmaceutical company developing novel oncology therapeutics together with drug-specific DRP companion diagnostics for personalized cancer care, reported encouraging initial results from its ongoing Phase 2 clinical trial evaluating the efficacy of its PARP inhibitor, stenoparib, in women with advanced ovarian cancer (AOC) (Press release, Allarity Therapeutics, DEC 5, 2023, View Source [SID1234638168]). Of the five evaluable patients included in the initial data analysis, one patient experienced a complete response and the other four demonstrated stable disease.

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Investigators prescreened women with AOC using Allarity’s DRP-Stenoparib CDx, a complex transcriptomic signature comprising 414 mRNA biomarkers indicative of response/resistance to the drug. Each woman was assigned a DRP-score, and those with scores above 50%, which suggested a higher likelihood of benefiting from treatment with stenoparib, were selected for treatment. Selected patients received stenoparib in a twice daily (BID) dosing regimen (200 mg morning, 400 mg evening) under a change in protocol, implemented earlier in the year, from prior once-daily dosing of 600 mg. Allarity implemented the protocol change to optimize the drug exposure taking into account the half-life of stenoparib in patients.

Of the 22 patients screened with the DRP-Stenoparib CDx, 17 DRP positive patients were identified. Eleven women have entered treatment, and among the five evaluable participants assessed up to the data evaluation cut-off, there were early signs of clinical benefit in all cases:

One patient experienced a complete response (CR) by scan (to be confirmed by second scan) and by decreased levels of CA125 (a biomarker of AOC).
One patient experienced stable disease with tumor shrinkage of 19%.
One patient experienced stable disease for more than 24 weeks with tumor
shrinkage of 11%.
Two patients experienced stable disease with tumor shrinkage of 8%.
All five patients had previously been treated with another PARP inhibitor. All five patients remain in treatment with stenoparib and the four that did not have complete responses are showing stable disease at this time.

"We are enthusiastic about these early, promising data since the observed clinical benefit indicates that stenoparib is active in advanced ovarian cancer patients selected with the DRP -Stenoparib CDx, even though these women had prior PARP inhibitor therapy and chemotherapy. While still early, these data suggest that BID dosing of this drug, and the use of the DRP -Stenoparib CDx for patient selection and treatment, may provide advanced ovarian cancer patients meaningful benefit. The DRP -Stenoparib CDx, if approved, may provide clinicians with an important diagnostic to guide patient treatment in this hard-to-treat patient population," said Marie Foegh, M.D., Chief Medical Officer of Allarity.

The initial data readout is from an ongoing Phase 2 open-label, single-arm trial that Allarity is conducting at multiple sites in the U.S. and Europe. The goal of the study is to evaluate the anti-tumor effect of stenoparib as monotherapy in DRP-selected patients with locally recurrent or metastatic ovarian cancer after previous PARP inhibitor and chemotherapy treatments. The primary endpoint is objective response rate (ORR). Allarity anticipates an interim data readout in Q1 2024.

The DRP-Stenoparib CDx is a transcriptomic signature comprising 414 mRNA biomarkers that are collectively predictive of tumor sensitivity or resistance to stenoparib. Using the DRP CDx to select likely responder patients while excluding likely resistant ones, Allarity aims to improve the benefit-risk ratio of stenoparib in metastatic or locally advanced ovarian cancer. The initial data from Allarity’s ongoing DRP-guided Phase 2 study of stenoparib suggests that the DRP-Stenoparib CDx may identify a subset of AOC patients previously treated with a PARP inhibitor who may benefit from treatment with stenoparib. The DRP-Stenoparib CDx is a clinical-stage companion diagnostic candidate and has not yet been approved by the U.S. FDA or the EU’s EMA.

All preliminary data are subject to change until the final study data readout. Early trial results may not be a reliable indicator of subsequent trial results based on a larger patient population.

About Stenoparib

Stenoparib is an orally-available, small molecule dual-targeted inhibitor of PARP1/2 and telomerase maintenance enzymes (Tankyrase 1 and 2). At present, tankyrases are attracting significant attention as emerging therapeutic targets for cancer, principally due to their role in the Wnt signaling pathway. Aberrant Wnt/β-catenin signaling has been implicated in the development and progression of multiple cancers, potentially giving stenoparib a unique, dual tumor inhibitory action. Stenoparib was originally developed by Eisai Co. Ltd. and was formerly known under the names E7449 and 2X-121. Allarity has the exclusive, global rights for the development and commercialization of stenoparib.

Some approved PARP inhibitors have recently been shown to be associated with less favorable survival outcomes than initially established. Allarity’s Phase 2 trial data for stenoparib to date shows that the drug has much less myelotoxicity than the FDA approved PARP inhibitors. Specifically, in 42 evaluable women in Phase 2 studies with stenoparib, anemia (21%), neutropenia (2%) and thrombocytopenia (0%) was lower than the approved PARP inhibitor niraparib with anemia 51%, neutropenia in 20% and thrombocytopenia oberved in in 52% of 463 patients. Allarity anticipates that this lower myelotoxicity may make stenoparib a better candidate for combination with other drugs. Allarity is studying the therapeutic potential of stenoparib in combination with dovitinib (a pan-targeted kinase inhibitor) in an ongoing Phase 1b trial, with an anticipated data readout near early Q2 2024. The Company believes that stenoparib may have broad therapeutic potential in combination with other anti-tumor agents.

On December 5, 2023 Checkpoint Therapeutics, Inc. ("Checkpoint") (Nasdaq: CKPT), a clinical-stage immunotherapy and targeted oncology company, reported that the U.S. Patent and Trademark Office ("USPTO") has issued a new patent (U.S. Patent No. 11,834,505) covering a method of treating various cancers, including cutaneous squamous cell carcinoma ("cSCC"), through the administration of cosibelimab (Press release, Checkpoint Therapeutics, DEC 5, 2023, View Source [SID1234638167]).

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The USPTO previously issued a composition of matter patent (U.S. Patent No. 10,590,199), specifically covering cosibelimab, or a fragment thereof. Together, these patents protect Checkpoint’s differentiated and potential best-in-class anti-PD-L1 antibody, cosibelimab, in the U.S. through at least May 2038, not including any potential patent term extension under the Hatch-Waxman Act.

Checkpoint’s Biologics License Application ("BLA") for cosibelimab is currently under review by the U.S. Food and Drug Administration ("FDA") as a potential new treatment for patients with locally advanced and metastatic cSCC, with an upcoming Prescription Drug User Fee Act ("PDUFA") goal date of January 3, 2024.

"With less than five weeks remaining before our assigned PDUFA date for cosibelimab, we look forward to cosibelimab potentially joining an approved class of immunotherapies with combined worldwide annual sales exceeding $35 billion," said James Oliviero, President and Chief Executive Officer of Checkpoint. "We believe our broad U.S. patent portfolio, expiring no earlier than May 2038, provides the potential for cosibelimab to be further developed into a market leading drug, not only in cSCC, but also in additional indications, both as a monotherapy and as the PD-L1 backbone for new combination regimens."

About Cosibelimab
Cosibelimab is a potential best-in-class, high affinity, fully-human monoclonal antibody of IgG1 subtype that directly binds to programmed death ligand-1 ("PD-L1") and blocks the PD-L1 interaction with the programmed death receptor-1 ("PD-1") and B7.1 receptors. Cosibelimab’s primary mechanism of action is based on the inhibition of the interaction between PD-L1 and its receptors PD-1 and B7.1, which removes the suppressive effects of PD-L1 on anti-tumor CD8+ T-cells to restore the cytotoxic T cell response. Cosibelimab is potentially differentiated from the currently marketed PD-1 and PD-L1 antibodies through sustained >99% target tumor occupancy to reactivate an antitumor immune response and the additional benefit of a functional Fc domain capable of inducing antibody-dependent cell-mediated cytotoxicity for potential enhanced efficacy in certain tumor types.

On December 5, 2023 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, reported interim results from an ongoing Phase 1b/2 clinical study of palazestrant (OP-1250) in combination with CDK4/6 inhibitor ribociclib, a Poster Spotlight Session on interim Phase 2 clinical data of palazestrant in combination with palbociclib, and a trials-in-progress poster for the OPERA-01 monotherapy Phase 3 pivotal trial at the San Antonio Breast Cancer Symposium (SABCS) at the Henry B. Gonzalez Convention Center in San Antonio, Texas (Press release, Olema Oncology, DEC 5, 2023, View Source [SID1234638165]). This disclosure was originally planned for December 7, 2023. However, on December 5, 2023, the 2023 San Antonio Breast Cancer Symposium (SABCS) published the posters ahead of schedule. These full data are scheduled to be presented on December 7, 2023, and copy of the posters are available now on Olema’s website under the Science section.

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"We believe the results we are presenting at SABCS demonstrate that palazestrant has key characteristics that make it a potential best-in-class endocrine therapy for ER+/HER2- breast cancer: complete antagonism of the estrogen receptor, favorable tolerability and tumor response, and attractive combinability with CDK4/6 inhibitors," said Sean P. Bohen, M.D., Ph.D., President and Chief Executive Officer of Olema Oncology. "OPERA-01, our Phase 3 monotherapy pivotal trial of palazestrant, has initiated, with multiple trial sites now activated and patient dosing started. The data we are gathering in our Phase 2 combination studies with CDK4/6 inhibitors, ribociclib and palbociclib, support the potential initiation of a pivotal first-line combination trial as early as the end of 2024, bringing us closer to achieving our goal of transforming the standard of care for women’s cancers."

Palazestrant Phase 1b/2 Study in Combination with Ribociclib: A 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" will be presented at SABCS. A more recent data cut, as of November 1, 2023, highlights the following:

•Across 19 patients who had completed at least one cycle of treatment as of the data cutoff date, the combination of up to 120 mg of palazestrant with 600 mg of ribociclib daily was well tolerated, with no safety signals or enhancement of toxicity and an overall safety profile remains consistent with the expected safety profile of ribociclib plus an endocrine therapy.
•Palazestrant did not affect ribociclib drug exposure in patients, and ribociclib had no clinically meaningful effect on palazestrant drug exposure.
•There were no dose-limiting toxicities, the maximum tolerated dose was not reached, and the majority of treatment-emergent adverse events were grade 1 or 2, with no grade 4 events observed. Neutropenia was reversible in all patients, and the timing was generally consistent with ribociclib-related neutropenia.
•Findings from this study support the continued use of palazestrant at the recommended Phase 2 dose of 120 mg in combination with 600mg of ribociclib, and enrollment in the dose-expansion portion of the study is ongoing.

Palazestrant Phase 1b/2 Study in Combination with Palbociclib: A poster titled "A Phase 1b/2 study of palazestrant (OP-1250), an oral complete estrogen receptor antagonist (CERAN) and selective ER degrader (SERD), with palbociclib in ER-positive, HER2-negative, advanced or metastatic breast cancer patients", will be presented in a Poster Spotlight Session by Prof. Arlene Chan, FRACP, MMed, Breast Cancer Research Centre-WA, Curtin University, Breast Clinical Trials Unit, Hollywood Private Hospital, Nedlands, Australia. The presentation will highlight that:

•
Across 46 patients as of the cutoff date of September 15, 2023, the combination of palazestrant (120 mg) with palbociclib (125 mg) daily was well tolerated, with an overall safety profile consistent with the expected safety profile of palbociclib plus an endocrine therapy.
•
There was no observed drug-drug interaction between palazestrant and palbociclib, and there was no induced metabolism or increase in exposure of either palbociclib or palazestrant when administered in combination. Most treatment-emergent adverse events were grade 1 or 2. Neutropenia incidence was similar to the PALOMA-3 study; it was reversible in all patients and the timing was generally consistent with the palbociclib-related neutropenia.
•
Tumor responses and prolonged disease stabilization were observed in this patient group, including in those previously exposed to CDK4/6 inhibitors, in both ESR1 mutant and ESR1 wild-type tumors. Partial responses were observed in seven patients, with two confirmed partial responses and five unconfirmed partial responses. The clinical benefit rate was 46% in all patients and 60% in patients with an ESR1 mutation at baseline. In patients naïve to prior CDK4/6 inhibitor treatment, the CBR was 71%. 53% of patients had any reduction in target lesion size.
•
Twenty-two (48%) patients remain on treatment, and efficacy data are still maturing. Findings from this study are consistent with previously reported data and support the ongoing clinical development of palazestrant in combination with CDK4/6 inhibitors for the treatment of ER+/HER2− metastatic breast cancer.

OPERA-01 Phase 3 Monotherapy Trial: Olema will present a poster titled "OPERA-01: A randomized, open-label, phase 3, study of palazestrant (OP-1250) vs standard-of-care treatment for ER+, HER2- advanced or metastatic breast cancer after endocrine and CDK4/6 inhibitor therapy", that detailed the ongoing clinical trial design, inclusion/exclusion criteria, and trial endpoints. Please find more details at www.opera-01.com or at clinicaltrials.gov (NCT06016738).

Company Investor Webcast and Conference Call

Olema will host a webcast and conference call for analysts and investors to review data presented at SABCS 2023 as well as other ongoing studies tomorrow, Wednesday, December 6, 2023, at 8:00 a.m. ET (7:00 a.m. CT). Please register for the webcast by visiting the Investors & Media section of Olema’s website at olema.com.