On January 30, 2023 Qurient Co. Ltd. (KRX: 115180), a clinical-stage biotech company based in Korea, reported that the first patient has been dosed in the Phase 1b/2 clinical study of Q702 in combination with KEYTRUDA (pembrolizumab) (Press release, Qurient Therapeutics, JAN 30, 2023, View Source [SID1234626655]).

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The Q702 Phase 1b/2 study (NCT05438420) is being conducted at seven investigative sites in the U.S. and Korea, and approximately 142 patients with advanced solid tumors are scheduled to be enrolled. The primary objectives of the Phase 1b/2 study are to determine the safety and efficacy of Q702 in combination with KEYTRUDA in study subjects with advanced solid cancers.

"We are pleased to initiate evaluation of Q702 in combination with KEYTRUDA for the treatment of esophageal, gastric, hepatocellular, and cervical cancers, where limited immuno-oncology treatment options are currently available," said Kiyean Nam, Ph.D., CEO of Qurient. "We have previously shown the potential additive benefit of Q702 in combination with anti-PD-1 therapy in preclinical models, and we expect the same clinical benefits of Q702 in combination with KEYTRUDA for patients."

About Q702

Q702 is an orally available novel Axl/Mer/CSF1R inhibitor and is designed to modulate innate immune components leading to T cell activation. Q702 was also shown to increase antigen presentation in the tumor cells demonstrating dual mode of action. A phase 1/2 clinical trial is currently underway in the U.S. (Clinical Trials.gov Identifier: NCT04648254) to evaluate safety and efficacy of Q702 as a monotherapy treatment for solid cancers.

On January 30, 2023 Oricell Therapeutics Co., Ltd (Oricell), an innovative pharmaceutical company committed to the development of clinical-stage oncology cell therapies, reported publication of data from a clinical study evaluating the efficacy of OriCAR-017, an autologous GPRC5D-directed CAR-T cell therapy, in the treatment of relapsed/refractory multiple myeloma (RRMM) in an article entitled "Phase 1 Open-Label Single-Centre Single Arm Study of GPRC5D CAR T Cells(OriCAR-017) in Patients with Relapsed/Refractory Multiple Myeloma (POLARIS)" in The Lancet Haematology (2022 impact factor: 30.153) (Press release, OriCell Therapeutics, JAN 30, 2023, View Source [SID1234626654]).

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The POLARIS study, the first-in-human study of OriCAR-017, explores the safety, tolerability and preliminary anti-tumor efficacy for a single intravenous infusion of OriCAR-017 in patients with RRMM (NCT05016778). As of June 30, 2022, the study had showed exciting clinical results for OriCAR-017 in the treatment of 10 patients with RRMM:

Median follow-up time: 238 days (range: 99-345 days)

Safety: Dose-limiting toxicities (DLTs), serious adverse events (SAEs), neurotoxicity and deaths were not observed. The common treatment-emergent AEs were Grade 3 or 4 hematologic toxicities, including neutropenia, leukopenia, thrombocytopenia and anemia. Cytokine release syndrome (CRS) was observed in all patients (9 patients in G1 and one patient in G2).

Preliminary clinical efficacy: the study revealed an impressive 100% overall response rate, with 60% stringent complete response and 40% very good partial response. All patients (100%) achieved MRD negative (10-5/ml). Additionally, of the 5 patients who relapsed after BCMA CAR T-cell therapy, 2 achieved stringent complete response and 3 achieved very good partial response. At the date cut-off time, the mPFS (median progression-free survival) has not yet been reached; for the 2 patients who had disease progression, one with GPRC5D-positive while the other one with GPRC5D-negative.
"Advances in the treatment of R/RMM, including the introduction of immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies as well as stem cell transplantation, have prolonged survival in R/RMM patients, the disease remains a clinically incurable plasma cell neoplasm," said Prof. He Huang, Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University. "Nevertheless, almost all R/RMM patients eventually experience one or more relapses, with poorer survival outcomes for those with high-risk cytogenetic characteristics or refractory diseases. Data from our study showed that with extraordinary clinical efficacy, OriCAR-017 has been proved to be a novel, safe and effective therapy for patients with R/RMM, especially for those who experienced a relapse after receiving BCMA-targeted therapy. We are looking forward to continuously conducting follow-up clinical studies of OriCAR-017 in concert with Oricell."

"OriCAR-017 has demonstrated 100% ORR and controllable safety in the POLARIS study, providing a solid foundation for Oricell’s subsequent registration of clinical studies," stated Helen Yang, Chairman and CEO of Oricell. "The firm is in the process of submitting an application in the US and China for the registration of clinical studies of OriCAR-017 while advancing the therapy to critical phases of clinical research as soon as possible."

About OriCAR-017

OriCAR-017, one of the key therapies developed by Oricell based on the company’s two proprietary technology platforms OriAb and OriCAR, is a GPRC5D-targeted CAR T-Cell therapy used to treat relapsed/refractory multiple myeloma (RRMM).

In June 2022, Oricell announced data from Phase I POLARIS clinical trial conducted by investigators in China at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting for 2022. As of April 30, 2022, all evaluable data of the study had showed 100% ORR as well as 100% minimal residual disease (MRD) negative rate as measured by flow cytometry (10-5) at day 28 after infusion in all participators, including those who relapsed following the BCMA CAR-T therapy.

In October 2022, OriCAR-017 received Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of RRMM.

Currently, the company is accelerating the registration of the therapy in both China and the US.

About Multiple Myeloma

Multiple myeloma (MM), one of the most common blood cancers, is a malignant disease of abnormal proliferation of clonal plasma cells. For newly treated MM patients, commonly used first-line treatment drugs include proteasome inhibitors, immunomodulatory drugs and alkylating agents. For most patients, the commonly used first-line treatments can stabilize the patient’s condition for 3-5 years, but a small number of patients show primary drug resistance at initial treatment, and the disease cannot be effectively controlled. Most of the newly treated patients with effective treatment will inevitably enter the relapse and refractory stage after the stable disease period. Therefore, there is still an unmet clinical need for patients with relapsed/refractory multiple myeloma. In the United States, MM accounts for nearly 2% of all new cancer cases and more than 2% of cancer deaths. (For more information, see View Source )

On January 30, 2023 Deka Biosciences ("Deka"), a biotech company focused on developing novel cytokine therapies to treat cancer and inflammatory diseases, reported that the U.S. Food and Drug Administration (FDA) has completed its review of the investigational new drug (IND) application for DK210 (EGFR) and concluded that Deka may proceed with a Phase 1 clinical trial in the United States (Press release, Deka Biosciences, JAN 30, 2023, View Source [SID1234626653]). The Phase 1, first-in-human, multicenter clinical study seeks to characterize the safety, and biomarkers for response of DK210 (EGFR) in patients with advanced solid cancer who are overexpressing epidermal growth factor receptors (EGFR) (NCT05704985).

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"Obtaining FDA clearance for our company’s first program to start clinical trials is a significant achievement," said Dr. John Mumm, CEO and co-founder of Deka. "We are excited to move forward with the clinical development of DK210 (EGFR) and the potential it holds for positively impacting the lives of many cancer patients."

DK210 (EGFR) is the first of several experimental therapeutics developed as part of Deka’s platform of molecules. Each DiakineTM in Deka’s platform consists of two cytokines coupled together onto a single chain variable fragment targeting system that enables the cytokines to accumulate more specifically into specific tissues. The combination of the two cytokines increases potency and reduces toxicity while the targeting system also improves the drug’s efficacy, safety, and manufacturability. Deka has identified genetic markers that are related to responses to each DiakineTM. These markers will be evaluated in early clinical trials with the hope of using them as potential diagnostic tools to match patients with the most effective DiakineTM treatment in later stage trials.

On January 30, 2023 Mickey Mikitani, Co-CEO of Rakuten Medical, Inc. reported a presentation to investors from around the world at the 41st Annual J.P. Morgan Healthcare Conference (JPM2023) on January 10, 2023, in San Francisco, California, U.S (Press release, Rakuten Medical, JAN 30, 2023, View Source;301734064.html [SID1234626652]). The presentation included an overview of Rakuten Medical’s third antibody-dye conjugate,"RM-0256," to potentially reach the clinic, an update on the pipeline as a whole including its second asset "RM-1995" which is already in the clinical stage, an overview of the commercial growth in Japan for the Alluminox treatment using its leading compound "ASP-1929", global expansion of the company leveraging the success in Japan, and key milestones for the next few years.

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RM-0256 – currently being evaluated in pre-clinical studies – is a conjugate of an anti-PD-L1 antibody and IRDye700DX (IR700), a light-activatable dye, that accumulates specifically on PD-L1-expressing cells. PD-L1 is a protein that inhibits the anti-cancer immune response by deactivating killer T cells, by binding to PD-1 which is abundantly expressed on the T cell surface.1 PD-L1 is expressed in many solid tumors such as melanoma, lung, urothelial, gastrointestinal, gynecological, breast, and head and neck, among others, helping these tumors evade the immune system.2 In addition to being present on tumor cells, PD-L1 is also expressed on suppressive immune cells within the tumor microenvironment such as tumor associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs).3 In pre-clinical studies, Alluminox therapy using RM-0256 has been observed to enable the accumulation of RM-0256 on PD-L1-expressing target cells followed by activation of the IR700 by illumination with 690nm non-thermal light, resulting in destruction of the target cells by its photochemical reaction. This reaction may lead to immunogenic cell death (ICD) and activation of an anti-cancer immune response. Furthermore, the anti-PD-L1 antibody itself comprising RM-0256 has been observed to inhibit the PD-L1:PD-1 interaction and may act systemically as an immune checkpoint inhibitor, further enhancing the anticancer immune response after light irradiation.

In Japan, commercial launch of ASP-1929 (brand name in Japan: Akalux) continues to accelerate. 230+ doctors at 100+ institutions have been certified to provide the novel treatment, leading to 200+ treatments being administered in the 2 years since launch. (*ASP-1929 is investigational outside of Japan.) Publications based on real world data in Japan, "Quality-of-Life Evaluation of Patients with Unresectable Locally Advanced or Locally Recurrent Head and Neck Carcinoma Treated with Head and Neck Photoimmunotherapy"4 and "Near-Infrared Photoimmunotherapy for Oropharyngeal Cancer,"5 indicated that the treatment using ASP-1929 achieved good disease control without decreasing the Quality of Life (QOL). (**ASP-1929 is investigational outside of Japan and these quality-of-life assessments are specific to the Japanese population studied.)

Leveraging on the data and knowledge that is being accumulated in Japan, Rakuten Medical is further pursuing global expansion. For India, where it has established a subsidiary in 2022, global phase III trial of ASP-1929 in locoregional recurrent head and neck squamous cell carcinoma (ASP-1929-301 / ClinicalTrials.gov Identifier: NCT03769506) is being prepared for initiation in the country. Subject to positive clinical trial results, ASP-1929 could be approved as early as 2025 in the U.S., Taiwan, India, and other countries. A number of pipeline milestones are expected in the next few years, including the initiation of RM-1995 and RM-0256 clinical trials and the progression of several clinical trials with ASP-1929.

Mickey started his J.P. Morgan presentation with the question "What kind of future would open up if we could kill only targeted cells?" and showcased the potential of Rakuten Medical’s investigational technology by saying "In the decade since I first encountered this therapy, which is completely different from existing treatments, we have been developing the technology at a tremendous pace. Our goal goes beyond establishing a position as a local treatment. Existing therapies have taken over a century to evolve and establish themselves as standards of care – we aim to achieve this same position for our technology on a much shorter timeline."

The slides and audio of Mickey’s presentation at JPM2023 are available for download at the following links.

Slides: View Source
Audio: View Source

On January 30, 2023 The Menarini Group ("Menarini"), a leading Italian pharmaceutical and diagnostics company, reported that the U.S. Food and Drug Administration (FDA) has approved ORSERDU for the treatment of postmenopausal women or adult men, with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy (Press release, STEMLINE THERAPEUTICS, JAN 30, 2023, View Source;advanced-or-metast-301733294.html [SID1234626651]). Stemline Therapeutics ("Stemline"), a wholly-owned subsidiary of the Menarini Group, headquartered in New York and focused on bringing transformational oncology treatments for cancer patients, will commercialize ORSERDU in the U.S.

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"The FDA approval of ORSERDU marks the first ever therapy for ER+, HER2- advanced or metastatic breast cancer patients with ESR1 mutations and we are very proud to offer a targeted therapy addressing this huge unmet need," commented Elcin Barker Ergun, Chief Executive Officer of the Menarini Group. "We are grateful to the patients, investigators and administrators who participated in the clinical trials that led to this remarkable innovation."

ORSERDU is approved under the FDA’s Priority Review and Fast Track designation based on the results of the registrational Phase III trial EMERALD, that demonstrated statistically significant progression-free survival (PFS) with elacestrant vs SOC endocrine monotherapy (fulvestrant, letrozole, anastrozole, exemestane), meeting both primary endpoints in all patients and in those patients whose tumors harbor ESR1 mutations.

In the group of patients whose tumors had ESR1 mutations, elacestrant reduced the risk of progression or death by 45% (PFS HR=0.55, 95% CI: 0.39, 0.77) vs SOC. A post-hoc analysis of the PFS results based on the duration of prior CDK4/6i inhibitors (CDK4/6i) usage was presented at San Antonio Breast Cancer Symposium (SABCS) in December 2022. The median PFS was 8.6 months on elacestrant vs 1.9 months for SOC, in those patients whose tumors harbored ESR1 mutations and had been treated with a CDK4/6i for at least 12 months.

Safety data is consistent with the other endocrine therapies. Most of the adverse events (AEs), including nausea and musculoskeletal pain were grade 1 and 2. No hematological safety signal was observed and none of the patients in either of the two treatment arms had sinus bradycardia.

"Advanced or metastatic ER+, HER2- breast cancer pre-treated with endocrine-based therapy remains an area of unmet medical need. The last endocrine therapy approved was about 20 years ago, and effective endocrine options for this patient population are needed," said Dr. Aditya Bardia, MD, MPH, Director of Breast Cancer Research at Mass General Cancer Center, Associate Professor at the Medicine Department at Harvard Medical School, and Principal Investigator for the EMERALD trial. "ESR1 mutations are a known driver of resistance to standard endocrine therapy, and so far, have been difficult to treat. The approval of elacestrant is welcomed as it offers a novel option for patients with ER+, HER2- metastatic breast cancer. This therapy targets the ESR1 mutations in metastatic breast cancer and provides patients with a convenient oral once-daily dose."

"Each year 300,000 Americans are diagnosed with breast cancer and metastatic breast cancer causes the vast majority of deaths from the disease: more than 43,000 annually. We urgently need new and better treatment options to extend and improve the lives of people with metastatic breast cancer," said Sonya Negley, Executive Director, Metavivor. "We are thrilled to see the approval of ORSERDU, a new oral endocrine therapy, for patients who have tumors that harbor ESR1 mutations, which are present in up to 40% of ER+, HER2- advanced or metastatic breast cancer. We advise patients to get tested for ESR1 mutations at progression in their metastatic treatment, so that their healthcare team can identify the right treatment options for their disease."

ORSERDU will soon be available in the United States. Stemline is committed to helping patients access ORSERDU and will be offering services to overcome access barriers. Stemline ARC, a patient support program is available to help guide eligible patients through the various aspects of getting started on treatment, from providing educational information to helping them understand their insurance coverage and identify potential financial assistance options. For more information, patients and healthcare professionals can call 1-833-4-STEMLINE (1-833-478-3654)

The Menarini Group obtained global licensing rights for elacestrant in July 2020 from Radius Health, Inc., who conducted the EMERALD study. With this approval, Radius will receive milestone payments and royalties from commercial sales. The Menarini Group is now fully responsible for global registration, commercialization, and further development activities for elacestrant.

About EMERALD Phase 3 Study (NCT03778931)
The EMERALD Phase 3 trial is a randomized, open label, active-controlled study evaluating elacestrant as second- or third-line monotherapy in ER+, HER2- advanced/metastatic breast cancer patients. The study enrolled 478 patients who had received prior treatment with one or two lines of endocrine therapy, including a CDK4/6 inhibitor. Patients in the study were randomized to receive either elacestrant or the investigator’s choice of an approved hormonal agent. The primary endpoints of the study were progression-free survival (PFS) in the overall patient population and in patients with estrogen receptor 1 gene (ESR1) mutations.

About ORSERDU (elacestrant)
The U.S. Food and Drug Administration (FDA) has approved ORSERDU for the treatment of postmenopausal women or adult men, with ER+, HER2-, ESR1-mutated, advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. The Marketing Authorization Application (MAA) is currently under review by the European Medicines Agency (EMA).

Elacestrant is also being investigated in several clinical trials in metastatic breast cancer disease, alone or in combination with other therapies: ELEVATE (NCT05563220); ELECTRA (NCT05386108); ELONA (NCT05618613); ELCIN (NCT05596409). Elacestrant is also planned to be evaluated in early breast cancer disease.

Full prescribing information can be found at www.orserdu.com

Important Safety Information

Warning and Precautions

Dyslipidemia: Hypercholesterolemia and hypertriglyceridemia occurred in patients taking ORSERDU at an incidence of 30% and 27%, respectively. The incidence of Grade 3 and 4 hypercholesterolemia and hypertriglyceridemia were 0.9% and 2.2%, respectively. Monitor lipid profile prior to starting and periodically while taking ORSERDU.

Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, ORSERDU can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the final dose.

Adverse Reactions

Serious adverse reactions occurred in 12% of patients who received ORSERDU. Serious adverse reactions in >1% of patients who received ORSERDU were musculoskeletal pain (1.7%) and nausea (1.3%). Fatal adverse reactions occurred in 1.7% of patients who received ORSERDU, including cardiac arrest, septic shock, diverticulitis, and unknown cause (one patient each).

The most common adverse reactions (>10%), including laboratory abnormalities, of ORSERDU were musculoskeletal pain (41%), nausea (35%), increased cholesterol (30%), increased AST (29%), increased triglycerides (27%), fatigue (26%), decreased hemoglobin (26%), vomiting (19%), increased ALT (17%), decreased sodium (16%), increased creatinine (16%), decreased appetite(15%), diarrhea(13%), headache (12%), constipation (12%), abdominal pain (11%), hot flush (11%), and dyspepsia (10%).

Drug interactions

Concomitant use with CYP3A4 Inducers and/or inhibitors: Avoid concomitant use of strong or moderate CYP3A4 inhibitors with ORSERDU. Avoid concomitant use of strong or moderate CYP3A4 inducers with ORSERDU.

Use in specific populations

Lactation: Advise lactating women to not breastfeed during treatment with ORSERDU and for 1 week after the last dose.

Hepatic Impairment: Avoid use of ORSERDU in patients with severe hepatic impairment (Child-Pugh C). Reduce the dose of ORSERDU in patients with moderate hepatic impairment (Child-Pugh B).

The safety and effectiveness of ORSERDU in pediatric patients have not been established.

To report SUSPECTED ADVERSE REACTIONS, contact Stemline Therapeutics, Inc. at 1-877-332-7961 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Indication
ORSERDU (elacestrant), 345 mg tablets, is indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.

For more information, please see the full Prescribing Information for ORSERDU here

About The Menarini Group
The Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of over $4 billion and over 17,000 employees. Menarini is focused on therapeutic areas with high unmet needs with products for cardiology, oncology, pneumology, gastroenterology, infectious diseases, diabetology, inflammation, and analgesia. With 18 production sites and 9 Research and Development centers, Menarini’s products are available in 140 countries worldwide. For further information, please visit www.menarini.com.