SOUTH SAN FRANCISCO, Calif., Jan. 4, 2024 /PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) today announced a collaboration with CONNECT, an international collaborative network of pediatric cancer centers, to conduct a Phase 2 clinical trial to evaluate REZLIDHIA® (olutasidenib) in combination with temozolomide as maintenance therapy in newly diagnosed pediatric and young adult patients with high-grade glioma (HGG) harboring an isocitrate dehydrogenase-1 (IDH1) mutation..

加利福尼亚州南旧金山，2024年1月4日/PRNewswire/--Rigel Pharmaceuticals，Inc.（纳斯达克：RIGL）今天宣布与国际儿科癌症中心合作网络CONNECT合作，进行2期临床试验，评估REZLIDHIA®（olutasidenib）联合替莫唑胺作为新诊断的儿童和年轻成人患有异柠檬酸脱氢酶-1（IDH1）突变的高级别胶质瘤（HGG）患者的维持治疗。。

Under the collaboration, CONNECT will include olutasidenib in CONNECT's TarGeT-D, a molecularly guided Phase 2 umbrella clinical trial for HGG.  The Rigel-sponsored arm will study post-radiotherapy administration of olutasidenib in combination with temozolomide followed by olutasidenib monotherapy as maintenance treatment in newly diagnosed pediatric and young adult patients (less than 39 years old) with IDH1 mutation positive HGG, including diffuse intrinsic pontine glioma (DIPG), an aggressive brain tumor with limited treatment options.

在合作下，CONNECT将在CONNECT的TarGeT-D中包括olutasidenib，这是一项针对HGG的分子引导的2期伞式临床试验。Rigel赞助的部门将研究放疗后给予olutasidenib联合替莫唑胺，然后进行olutasidenib单药治疗，作为IDH1突变阳性HGG（包括弥漫性固有桥脑胶质瘤（DIPG））的新诊断儿科和年轻成年患者（39岁以下）的维持治疗，一种侵袭性脑肿瘤，治疗选择有限。

Rigel will provide funding up to $3 million and study material over the four-year collaboration..

里格尔将在四年的合作中提供高达300万美元的资金和研究材料。。

'We are excited to collaborate with CONNECT to evaluate olutasidenib in high grade glioma,' said Raul Rodriguez, Rigel's president and CEO. 'We believe olutasidenib has potential in a variety of cancers where mIDH1 plays an important role and we look forward to generating new data in this disease state, which has a high unmet need.

里格尔总裁兼首席执行官劳尔·罗德里格斯（RaulRodriguez）说，我们很高兴与CONNECT合作，评估奥拉西德尼（olutasidenib）治疗高级别胶质瘤的疗效我们认为，olutasidenib在mIDH1发挥重要作用的多种癌症中具有潜力，我们期待着在这种疾病状态下产生新的数据，这种疾病的需求尚未得到满足。

This collaboration builds on our hematology-oncology pipeline expansion strategy and enables us to explore the potential of olutasidenib in a focused and efficient manner.'.

这种合作建立在我们的血液肿瘤学管道扩张战略的基础上，使我们能够以专注和有效的方式探索olutasidenib的潜力。”。

This open label Phase 2 trial will be overseen by Drs. Santosh Valvi and Nicholas Gottardo, Perth Children's Hospital, Dr. Michael J Fisher, Children's Hospital of Philadelphia, and Dr. Maryam Fouladi, Nationwide Children's Hospital, and aims to enroll approximately 60 patients. The primary objective of the olutasidenib arm of the trial is to estimate progression-free survival.

这项开放标签的2期试验将由珀斯儿童医院的Santosh Valvi博士和Nicholas Gottardo博士，费城儿童医院的Michael J Fisher博士和全国儿童医院的Maryam Fouladi博士监督，旨在招募大约60名患者。该试验的olutasidenib组的主要目标是估计无进展生存期。

The study will also characterize the safety, tolerability, and pharmacokinetics of olutasidenib in pediatric and young adult patients. The study is estimated to begin enrolling patients in the first half of 2024 and will fulfill Rigel's post-marketing pediatric study requirement related to the FDA approval of REZLIDHIA in relapsed or refractory (R/R) AML..

该研究还将表征olutasidenib在儿科和年轻成人患者中的安全性，耐受性和药代动力学。该研究预计将于2024年上半年开始招募患者，并将满足Rigel的上市后儿科研究要求，该要求与FDA批准REZLIDHIA治疗复发或难治性（R/R）AML有关。。

In January 2023, data was published in the peer-reviewed journal Neuro-Oncology from a multicenter, open label, Phase 1b/2 trial of 26 patients with R/R and predominantly enhancing gliomas harboring an IDH1 mutation. The data showed that olutasidenib 150 mg BID was well tolerated and demonstrated preliminary evidence of clinical activity and prolonged disease control in this heavily pretreated population.  The authors noted that olutasidenib is a potent, brain-penetrant, selective inhibitor of mutant IDH1.1 The paper, titled 'Olutasidenib (FT-2102) in patients with relapsed or refractory IDH1-mutant glioma: A multicenter, open-label, phase Ib/II trial' can be accessed here..

2023年1月，来自26名R/R患者的多中心，开放标签，1b/2期试验的数据发表在同行评审的《神经肿瘤学》杂志上，该试验主要增强了携带IDH1突变的神经胶质瘤。数据显示，olutasidenib 150 mg BID具有良好的耐受性，并证明了在这种经过严重预处理的人群中具有临床活性和延长疾病控制时间的初步证据。作者指出，olutasidenib是突变IDH1.1的有效，脑渗透性，选择性抑制剂。该论文名为“复发或难治性IDH1突变胶质瘤患者的olutasidenib（FT-2102）：多中心，开放标签，Ib/II期试验”可以在这里访问。。

REZLIDHIA is FDA-approved for the treatment of adult patients with R/R acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test.

REZLIDHIA被FDA批准用于治疗成年R/R急性髓细胞白血病（AML）患者，该患者通过FDA批准的测试检测到易感IDH1突变。

About REZLIDHIA®INDICATIONREZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.

关于REZLIDHIA®适应症REZLIDHIA用于治疗成人复发或难治性急性髓细胞白血病（AML）患者，该患者通过FDA批准的测试检测到易感异柠檬酸脱氢酶-1（IDH1）突变。

IMPORTANT SAFETY INFORMATION

重要安全信息

WARNING: DIFFERENTIATION SYNDROMEDifferentiation syndrome, which can be fatal, can occur with REZLIDHIA treatment. Symptoms may include dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, hypotension, fever, and weight gain. If differentiation syndrome is suspected, withhold REZLIDHIA and initiate treatment with corticosteroids and hemodynamic monitoring until symptom resolution.

警告：分化综合征REZLIDHIA治疗可能会发生致命的分化综合征。症状可能包括呼吸困难，肺部浸润/胸膜心包积液，肾损伤，低血压，发烧和体重增加。如果怀疑有分化综合征，则停止使用REZLIDHIA，并开始使用皮质类固醇和血流动力学监测进行治疗，直到症状消退。

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WARNINGS AND PRECAUTIONSDifferentiation SyndromeREZLIDHIA can cause differentiation syndrome. In the clinical trial of REZLIDHIA in patients with relapsed or refractory AML, differentiation syndrome occurred in 16% of patients, with grade 3 or 4 differentiation syndrome occurring in 8% of patients treated, and fatalities in 1% of patients.

警告和预防分化综合征rezlidhia可引起分化综合征。在复发或难治性AML患者的REZLIDHIA临床试验中，分化综合征发生率为16%，3或4级分化综合征发生率为8%，死亡率为1%。

Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal. Symptoms of differentiation syndrome in patients treated with REZLIDHIA included leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, fever, edema, pyrexia, and weight gain.

分化综合征与骨髓细胞的快速增殖和分化有关，可能危及生命或致命。REZLIDHIA治疗患者的辨证症状包括白细胞增多，呼吸困难，肺浸润/胸膜心包积液，肾损伤，发热，水肿，发热和体重增加。

Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dose interruption of REZLIDHIA. Differentiation syndrome occurred as early as 1 day and up to 18 months after REZLIDHIA initiation and has been observed with or without concomitant leukocytosis..

在经历分化综合征的25例患者中，19例（76%）在治疗后或雷兹利迪亚剂量中断后恢复。分化综合征最早发生在REZLIDHIA发作后1天至18个月，并且已经观察到伴有或不伴有白细胞增多症。。

If differentiation syndrome is suspected, temporarily withhold REZLIDHIA and initiate systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours) for a minimum of 3 days and until resolution of signs and symptoms. If concomitant leukocytosis is observed, initiate treatment with hydroxyurea, as clinically indicated.

如果怀疑有分化综合征，则暂时停止服用REZLIDHIA并开始使用全身皮质类固醇（例如，每12小时静脉注射地塞米松10 mg），持续至少3天，直到体征和症状消失。如果观察到伴随的白细胞增多，请按照临床指示开始用羟基脲治疗。

Taper corticosteroids and hydroxyurea after resolution of symptoms. Differentiation syndrome may recur with premature discontinuation of corticosteroids and/or hydroxyurea treatment. Institute supportive measures and hemodynamic monitoring until improvement; withhold dose of REZLIDHIA and consider dose reduction based on recurrence..

症状缓解后减少皮质类固醇和羟基脲。分化综合征可能会因过早停用皮质类固醇和/或羟基脲治疗而复发。制定支持措施和血流动力学监测直至改善；保留REZLIDHIA的剂量，并考虑根据复发减少剂量。。

HepatotoxicityREZLIDHIA can cause hepatotoxicity, presenting as increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased blood alkaline phosphatase, and/or elevated bilirubin. Of 153 patients with relapsed or refractory AML who received REZLIDHIA, hepatotoxicity occurred in 23% of patients; 13% experienced grade 3 or 4 hepatotoxicity.

肝毒性rezlidhia可引起肝毒性，表现为丙氨酸氨基转移酶（ALT）升高，天冬氨酸氨基转移酶（AST）升高，血液碱性磷酸酶升高和/或胆红素升高。在接受REZLIDHIA治疗的153例复发或难治性AML患者中，23%的患者发生肝毒性；13%经历了3级或4级肝毒性。

One patient treated with REZLIDHIA in combination with azacitidine in the clinical trial, a combination for which REZLIDHIA is not indicated, died from complications of drug-induced liver injury. The median time to onset of hepatotoxicity in patients with relapsed or refractory AML treated with REZLIDHIA was 1.2 months (range: 1 day to 17.5 months) after REZLIDHIA initiation, and the median time to resolution was 12 days (range: 1 day to 17 months).

在临床试验中，一名接受雷兹利迪亚联合阿扎胞苷治疗的患者因药物性肝损伤并发症死亡，该联合治疗未显示雷兹利迪亚。REZLIDHIA治疗复发或难治性AML患者肝毒性发作的中位时间为REZLIDHIA开始后1.2个月（范围：1天至17.5个月），中位缓解时间为12天（范围：1天至17个月）。

The most common hepatotoxicities were elevations of ALT, AST, blood alkaline phosphatase, and blood bilirubin..

最常见的肝毒性是ALT，AST，血液碱性磷酸酶和血液胆红素升高。。

Monitor patients frequently for clinical symptoms of hepatic dysfunction such as fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. Obtain baseline liver function tests prior to initiation of REZLIDHIA, at least once weekly for the first two months, once every other week for the third month, once in the fourth month, and once every other month for the duration of therapy.

经常监测患者肝功能障碍的临床症状，如疲劳、厌食、右上腹部不适、尿黑或黄疸。在开始REZLIDHIA之前，至少在前两个月每周进行一次基线肝功能检查，在第三个月每隔一周进行一次，在第四个月进行一次，在治疗期间每隔一个月进行一次。

If hepatic dysfunction occurs, withhold, reduce, or permanently discontinue REZLIDHIA based on recurrence/severity..

如果发生肝功能障碍，则根据复发/严重程度停止，减少或永久停止REZLIDHIA。。

ADVERSE REACTIONSThe most common (≥20%) adverse reactions, including laboratory abnormalities, were aspartate aminotransferase increased, alanine aminotransferase increased, potassium decreased, sodium decreased, alkaline phosphatase increased, nausea, creatinine increased, fatigue/malaise, arthralgia, constipation, lymphocytes increased, bilirubin increased, leukocytosis, uric acid increased, dyspnea, pyrexia, rash, lipase increased, mucositis, diarrhea and transaminitis..

不良反应包括实验室异常在内的最常见（≥20%）的不良反应是天冬氨酸转氨酶升高，丙氨酸转氨酶升高，钾降低，钠降低，碱性磷酸酶升高，恶心，肌酐升高，疲劳/不适，关节痛，便秘，淋巴细胞增加，胆红素升高，白细胞增多，尿酸升高，呼吸困难，发热，皮疹，脂肪酶增加，粘膜炎，腹泻和转氨酶。。

DRUG INTERACTIONS

药物相互作用

Avoid concomitant use of REZLIDHIA with strong or moderate CYP3A inducers.

避免将REZLIDHIA与强或中度CYP3A诱导剂同时使用。

Avoid concomitant use of REZLIDHIA with sensitive CYP3A substrates unless otherwise instructed in the substrates prescribing information. If concomitant use is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

除非底物处方信息中另有说明，否则避免将REZLIDHIA与敏感的CYP3A底物同时使用。如果不可避免地同时使用，请监测患者这些药物的治疗效果丧失。

LACTATIONAdvise women not to breastfeed during treatment with REZLIDHIA and for 2 weeks after the last dose.

哺乳期建议女性在服用REZLIDHIA期间和最后一次服用后2周内不要母乳喂养。

GERIATRIC USENo overall differences in effectiveness were observed between patients 65 years and older and younger patients. Compared to patients younger than 65 years of age, an increase in incidence of hepatotoxicity and hypertension was observed in patients ≥65 years of age.

老年人使用65岁以上和年轻患者之间没有观察到总体有效性差异。与65岁以下的患者相比，≥65岁的患者肝毒性和高血压的发生率增加。

HEPATIC IMPAIRMENTIn patients with mild or moderate hepatic impairment, closely monitor for increased probability of differentiation syndrome.

肝损伤轻度或中度肝损伤患者，密切监测分化综合征的可能性增加。

Click here for Full Prescribing Information, including Boxed WARNING.

单击此处查看完整的处方信息，包括盒装警告。

To report side effects of prescription drugs to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088 (800-332-1088).

要向FDA报告处方药的副作用，请访问www.FDA.gov/medwatch或致电1-800-FDA-1088（800-332-1088）。

REZLIDHIA is a registered trademark of Rigel Pharmaceuticals, Inc.

REZLIDHIA是Rigel Pharmaceuticals，Inc.的注册商标。

About Rigel Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) is a biotechnology company dedicated to discovering, developing and providing novel therapies that significantly improve the lives of patients with hematologic disorders and cancer. Founded in 1996, Rigel is based in South San Francisco, California.

关于Rigel Rigel Pharmaceuticals，Inc.（纳斯达克股票代码：RIGL）是一家生物技术公司，致力于发现、开发和提供新疗法，以显着改善血液病和癌症患者的生活。里格尔成立于1996年，总部位于加利福尼亚州南旧金山。

For more information on Rigel, the Company's marketed products and pipeline of potential products, visit www.rigel.com. .

有关Rigel、该公司已上市产品和潜在产品渠道的更多信息，请访问 www.rigel.com。

About CONNECTCONNECT is an international collaborative network of pediatric cancer centers with the objective to improve outcomes for children with brain tumors. CONNECT conducts small, scientifically rational, pilot and early phase studies to assess feasibility and early efficacy of incorporating promising new therapies into established frontline therapeutic regimens.

关于CONNECTCONNECT是一个儿科癌症中心的国际合作网络，旨在改善脑瘤儿童的预后。CONNECT进行小型，科学合理的试点和早期研究，以评估将有前途的新疗法纳入既定一线治疗方案的可行性和早期疗效。

For more information on CONNECT, visit connectconsortium.org..

有关CONNECT的更多信息，请访问connectconsortium.org。。

de la Fuente M, et al. Olutasidenib (FT-2102) in patients with relapsed or refractory IDH1-mutant glioma: A multicenter, open-label, phase Ib/II trial. Neuro Oncol. 2023 Jan 5;25(1):146-156. doi: 10.1093/neuonc/noac139.

de la Fuente M等人，复发或难治性IDH1突变胶质瘤患者的Olutasidenib（FT-2102）：一项多中心，开放标签，Ib/II期试验。神经肿瘤学。2023年1月5日；25（1）：146-156。doi:10.1093/neuonc/noac139。

Forward Looking Statements This press release contains forward-looking statements relating to, among other things, that olutasidenib may provide a meaningful approach to the treatment of patients with glioma, the enrollment of patients in the Phase 2 study of olutasidenib, and the use of the safety and efficacy data from the Phase 2 study of olutasidenib in glioma.

前瞻性声明本新闻稿包含前瞻性声明，其中涉及奥拉西地尼可能为神经胶质瘤患者的治疗提供有意义的方法，奥拉西地尼2期研究患者的登记，以及使用奥拉西地尼在神经胶质瘤中的2期研究的安全性和有效性数据。

Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Forward-looking statements can be identified by words such as 'aims', 'expected', 'explore' 'potential', 'look forward', 'believe', 'will' and similar expressions in reference to future periods.

本新闻稿中包含的任何不属于历史事实声明的声明都可能被视为前瞻性声明。前瞻性陈述可以通过诸如“目标”、“预期”、“探索”、“潜力”、“展望”、“相信”、“意志”等词语以及涉及未来时期的类似表达来识别。

Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on Rigel's current beliefs, expectations, and assumptions and hence they inherently involve significant risks, uncertainties and changes in circumstances that are difficult to predict and many of which are outside of our control. Therefore, you should not rely on any of these forward-looking statements.

前瞻性陈述既不是历史事实，也不是未来表现的保证。相反，它们是基于里格尔目前的信念、期望和假设，因此它们固有地涉及难以预测的重大风险、不确定性和环境变化，其中许多超出了我们的控制范围。因此，您不应该依赖这些前瞻性陈述。

Actual results and the timing of events could differ materially from those anticipated in such forward looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with  the FDA, European Medicines Agency, PMDA or other regulatory authorities may make adverse decisions regarding  olutasidenib; risks that clinical trials may not be predictive of real-world results or of results in subsequent clinical trials; risks that  olutasidenib may have unintended side effects, adverse reactions or incidents of misuses; the availability of resources to develop Rigel's product candidates; market competition; .

由于这些风险和不确定性，实际结果和事件发生的时间可能与此类前瞻性声明中预期的结果有很大不同，这些风险和不确定性包括但不限于与FDA、欧洲药品管理局、PMDA或其他监管机构相关的风险和不确定性，可能会对olutasidenib做出不利决定；临床试验可能无法预测实际结果或后续临床试验结果的风险；olutasidenib可能产生意外副作用，不良反应或误用事件的风险；开发Rigel候选产品的资源可用性；市场竞争。

Investors & Media Contacts:Investors:Rigel Pharmaceuticals, Inc.650.624.1232[email protected]

投资者和媒体联系人：投资者：Rigel Pharmaceuticals，Inc.650.624.1232[受电子邮件保护]

Media:David RosenArgot PartnersPhone: 212.600.1902Email: [email protected]

媒体：David RosenArgot Partners电话：212.600.1902邮件：[受电子邮件保护]

SOURCE Rigel Pharmaceuticals, Inc.

来源Rigel Pharmaceuticals，Inc。