PEG-Irinotecan

BriaCell doubles Progression-Free-Survival (PFS) and Clinical Benefit Rate vs historical results in the literatureBria-IMT™ PFS compares favorably to PFS of most recent treatment in 48% of Antibody-Drug Conjugate (ADC) resistant patientsTherapy well-tolerated with no Bria-IMT™ related discontinuationsClinical data highlight significant potential of Bria-IMT™ in advanced metastatic breast cancerSuperiority of selected Phase 3 regimen and formulation confirmedOral presentation by Mayo Clinic Professor and Principal Investigator, Saranya Chumsri, MD, on Monday June 3; 11:30 AM-1:00 PM CDT PHILADELPHIA and VANCOUVER, British Columbia, June 03, 2024 (GLOBE NEWSWIRE) -- BriaCell Therapeutics Corp. (Nasdaq: BCTX, BCTXW) (TSX: BCT) (“BriaCell” or the “Company”), a clinical-stage biotechnology company that develops novel immunotherapies to transform cancer care, announces positive clinical efficacy data updates of its ongoing randomized Phase 2 study evaluating lead clinical candidate Bria-IMT™ in patients with advanced metastatic breast cancer. Two poster sessions, one abstract, and one oral presentation session (by Principal Investigator and Professor of Oncology, Mayo Clinic, Saranya Chumsri, MD), will be presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting taking place today June 3, 2024 at McCormick Place, Chicago, IL. “We are very impressed with both clinical efficacy and safety data in these heavily pretreated patients. Given the limited effective treatment options in this group of patients, and the fact that most treatments are associated with significant toxicities, physicians and patients often opt to decline further ineffective and toxic drugs in lieu of palliative care,” Saranya Chumsri, MD, Principal Investigator and Professor of Oncology, Mayo Clinic. “Antibody-drug conjugates (ADCs) and immune checkpoint Inhibitors (CPIs) have emerged as the latest therapies to treat these patients. However, a large percentage of late-stage patients do not respond, and all patients inevitably develop resistance to them, making a safe and effective treatment an urgent medical need. BriaCell’s novel immunotherapy offers a well-tolerated treatment option for these patients beyond the currently approved drugs.” “While immunotherapy has emerged as an active treatment option for multiple cancer types, its use in breast cancer is rather restricted to a minority of patients. Discovering new strategies, in order to enhance the responsiveness of various subtypes of breast cancer to immunotherapy, presents as a therapeutic opportunity. Through its unique mechanism of action, Bria-IMT™ regimen selectively activates adaptive cancer-fighting CD4+ and CD8+ T cells and innate responses (dendritic and NK cells) to activate patients’ immune systems without producing serious side effects,” stated Carmen Calfa, M.D., Clinical Research Lead for the breast site disease group at the University of Miami Miller School of Medicine, Co-Director of the Cancer Survivorship Program at Sylvester Comprehensive Cancer Center, and Principal Clinical Investigator of the Phase 2 Bria-IMT™ study. “Our ASCO presentations highlight how Bria-IMT™’s activities – through diverse mechanisms including adaptive and innate responses - synergize with multiple mechanisms of action of checkpoint inhibitors,” stated Dr. Williams, BriaCell’s President and CEO. “We believe Bria-IMT™ has the potential to become a breakthrough novel treatment option for patients in advanced metastatic breast cancer.” The details of the presentations are summarized below. Oral Presentation Summary Abstract Number for Publication: 1022Title: Outcomes of advanced/metastatic breast cancer (aMBC) treated with Bria-IMT™, an allogeneic whole cell immunotherapy.Session Type and Title: Rapid Oral Abstract – Breast Cancer—MetastaticSession Date and Time: 6/3/2024; 11:30 AM-1:00 PM CDT This presentation details the results of BriaCell’s randomized Phase 2 study of Bria-IMT™ in combination with retifanlimab, an immune checkpoint inhibitor (CPI). The goal of randomization was to compare whether administration of the CPI early, in the first cycle of therapy, or later, late in the second cycle of therapy, offered any advantage. Two different formulations of Bria-IMT™ were also evaluated; one treated with interferon gamma and one untreated. The patients entering the study were very heavily pretreated and had failed multiple prior therapies as shown in the Table 1 below. Table 1. Prior Therapies in the Bria-IMT™ Phase 2 Study Previous TherapiesNumber of Patients (%)Antibody-Drug Conjugates (ADC)23 (44%)Immune Checkpoint Inhibitor (CPI)11 (20%)Cyclin-Dependent Kinase (CDK) 4/6 Inhibitors34 (63%) A total of 54 patients were included in the Phase 1/2 study. Nearly half of these had been treated previously with an antibody drug conjugate and had progressed in their disease following this treatment. Another 20% had failed a prior immune checkpoint inhibitor. Nearly 2/3 of the patients had failed therapy with a CDK 4/6 inhibitor. On average they had failed six prior therapy attempts. In the Phase 2 portion of the study, there were 32 patients with 16 treated with CPI early and 16 treated with CPI late. There was no statistically significant difference in progression-free survival (PFS) two groups. However, a slight advantage in the CPI early group has led this to be the selected regimen for the Phase 3 study. In the entire Phase 1/2 experience, with 54 patients, the formulation not incubated with interferon gamma showed a statistically significant improvement in PFS. Therefore, this formulation was selected for the Phase 3 study. The data are shown in Figure 1. Figure 1. Effect of treatment sequence and formulation on PFS Clinical benefit was seen in 55% of evaluable patients across all subtypes of breast cancer as shown in Figure 2 below. Figure 2: Objective Response Rate (ORR) and Clinical Benefit Rate (CBR) in the Bria-IMT™ Phase 1/2 Study The progression free survival rate and the clinical benefit rate as well as the objective response rate were markedly higher than those of similar patients treated with the treatment of their physician’s choice in other studies. Notably, “Treatment of Physician’s Choice” (TPC) will be the comparator in the Phase 3 study of Bria-IMT™. This is noted in Table 2 below. Table 2. Comparative PFS, ORR and CBR in Similar Patients StudyPrior Lines ofTherapy(median, range)PFS(months)ORR(%)CBR(%)BriaCell's Phase 2 study patients who received pivotal Phase 3 study formulation 6 (2-13)3.99.5*55*BriaCell's ADC Resistant Phase 2 patients who received pivotal Phase 3 study formulation 6 (3-13)4.112**53**Bardia, A. et. al. 14 (2-14)1.748Tripathy D. et. al. 2≥4 in 91%1.9310 O'Shaughnessy J. et. al. non-TNBC 35 (2-14)2.347 O'Shaughnessy J. et. al. TNBC 34 (2-10)1.6510 *Data is for evaluable patients, n=42 with 12 not evaluable. ** Data is for evaluable patients, n = 17 with 6 not evaluable.References: Data is shown for the intent to treat population for the control group treated with treatment of physician’s choice, which is the comparator in the BriaCell Phase 3 study1. Bardia A, et al. J Clin Oncol. 2024 May 20;42(15):1738-1744. 2. Tripathy D, et al. JAMA Oncol. 2022 Nov 1;8(11):1700-1701. jamaoncol.2022.4346. PMID: 36136348. This paper describes patients with brain metastases.3. O'Shaughnessy J, et al. Breast Cancer Res Treat. 2022 Sep;195(2):127-139. For additional detailed information of the clinical data on the oral presentation, please visit BriaCell Doubles Progression-Free-Survival (PFS) and Reports Clinical Benefit Data at ASCO 2024. Poster Presentation Summary The first poster described BriaCell’s ongoing pivotal Phase 3 registrational study in advanced metastatic breast cancer. BriaCell is excited to collaborate on this important program with authors and BriaCell medical advisory board members Sara A. Hurvitz, MD, Professor of Medicine, Fred Hutchinson Cancer Center, Adam M. Brufsky, MD, PhD, Professor of Medicine, University of Pittsburgh School of Medicine, and Massimo Cristofanilli, MD, Professor of Medicine, Weill Cornell Medical College, Cornell University. The second poster described clinical data of Bria-IMT™ in metastatic breast cancer patients who failed antibody drug conjugates (ADCs) and is spearheaded by Chaitali Nangia, MD, Partner, Hoag Medical Group, and Carmen Calfa, MD, Professor of Medicine, University of Miami.Abstract Number for Publication: TPS1137Title: Study of the Bria-IMT™ regimen and CPI vs physicians' choice in advanced metastatic breast cancer (BRIA-ABC).Based on Phase 2 clinical data showing numerous survival and clinical benefit outcomes in advanced breast cancer patients treated with the Bria-IMT™ regimen, the pivotal Phase 3 study has been designed as a multicenter randomized, open label comparison of the Bria-IMT™ regimen plus CPI in one arm versus Treatment of Physicians' Choice (TPC) in metastatic breast cancer patients with no approved alternative therapies available. Patients’ eligibility includes treatment with 2 or more prior regimens. There will be another arm of the Bria-IMT™ regimen alone (monotherapy). For additional information on the pivotal Phase 3 study, please visit ClinicalTrials.gov as NCT06072612. Abstract Number for Publication: 1087Title: SV-BR-1-GM after progression on ADC in patients with metastatic breast cancer. Remarkable progression-free survival and clinical benefit of Bria-IMT™ in ADC resistant advanced metastatic breast cancer Phase 2 clinical data of the Bria-IMT™ regimen in 23 advanced metastatic breast cancer patients who failed multiple prior treatments including ADCs and CPIs (median of 6 prior treatments) are presented. Clinical efficacy In evaluable patients, the ORR was 12% and CBR was 53% which is remarkable versus similar data suggesting clinical benefit.Median PFS of 4.1 months with the Phase 3 formulation was ~twice that seen of patients in similar studies - 1.71 and 2.23 months - who received TPC. The PFS results suggest superior clinical efficacy given the larger number of prior treatments (median of 6) in Bria-IMT™ patients vs those of the other studies (median of 4).Subset specific clinical benefits: Study data to date suggests clinical benefit for multiple breast cancer subtypes including HR+/HER2- (the most common breast cancer subtype, testing positive for estrogen and/or progesterone receptors and negative for human epidermal growth factor receptor 2 or HER2) with a CBR following treatment, of 63% (5 of 8 patients); HER2+ subtype (a positive test for HER2) with a 100% CBR (2 of 2 patients) and HR-/HER2 low subtype (a negative test for estrogen and/or progesterone receptor and a negative test for HER2) showing a CBR of 66% (2 of 3 patients). See Table 3. Table 3: Treatment Efficacy by Metastatic Breast Cancer Subtype in ADC-resistant patients HistologyAll Patients (N)Evaluable (N) PatientsBest ORRBest CBRAll ADC Resistant231712% (2 / 17)53% (9 / 17)ER/PR + / HER2 low or -8813% (1 / 8)63% (5 / 8)HER2+3250% (1 / 2)100% (2 / 2)TNBC127029% (2 / 7) Bria-IMT™ showed potential survival advantage over penultimate treatment in 48% of patients, likely by reversing immune exhaustion in patients irrespective of specific prior ADC. Safety profile Absence of both interstitial lung disease (ILD), a common serious adverse event with ADCs, and Bria-IMT™-related treatment discontinuations underscore Bria-IMT™'s excellent tolerability and favorable safety profile. In summary, the data to date shows that Bria-IMT™ offers extended progression-free survival and clinical benefit in heavily pre-treated, ADC resistant breast cancer patients versus those in other similar studies. BriaCell is closely monitoring ADC resistant patients in its ongoing pivotal Phase 3 study of Bria-IMT™ and CPI in advanced metastatic breast cancer. Title: Differential efficacy of SV-BR-1-GM in inducing intracranial metastasis regression. Superior clinical benefit of Bria-IMT™ regimen - alone or combined with an immune check point inhibitor (CPI) in advanced breast cancer patients with CNS metastatic disease Central nervous system (CNS) metastases, including brain metastases and other intracranial metastases, is a dire clinical situation with very poor survival. Very few therapies have shown any effect on CNS or intracranial metastases in breast cancer and it is a serious unmet medical need. Clinical efficacy: 83% (5/6) intracranial objective response rate (iORR) was reported in evaluable patients with central nervous system (CNS) metastases treated with the Bria-IMT™ regimen, either alone or in combination with an immune checkpoint inhibitor (i.e. PD-1 inhibitor pembrolizumab or retifanlimab). These patients failed multiple prior treatments including 2 antibody-drug conjugates in one case. This is illustrated in Figure 3. Figure 3. Intracranial Tumor Responses in Patients with Intracranial Metastases Treated with Bria-IMT™ Tumor reductions (≥30% reduction in the sum of diameters) were observed in heavily pretreated patients highlighting potential clinical benefit of Bria-IMT™ in managing CNS metastasesThis is a pre-planned subgroup analysis in the pivotal Phase 3 study of Bria-IMT™ providing another opportunity for approval Safety profile: No treatment related discontinuation was reported. In summary, Bria-IMT™’s tumor reductions observed in patients with intracranial disease underlines its potential clinical effectiveness in managing CNS metastatic disease in advanced breast cancer. BriaCell will continue to monitor the data in this subgroup of patients in its ongoing pivotal Phase 3 study in advanced metastatic breast cancer. Treatment of patients with CNS metastatic disease represents a potential additional indication for market approval of Bria-IMT™. Copies of the poster presentations and abstracts are posted on https://briacell.com/scientific-publications/. References Bardia A, et al. Final Results From the Randomized Phase III ASCENT Clinical Trial in Metastatic Triple-Negative Breast Cancer and Association of Outcomes by Human Epidermal Growth Factor Receptor 2 and Trophoblast Cell Surface Antigen 2 Expression. J Clin Oncol. 2024 May 20;42(15):1738-1744. doi: 10.1200/JCO.23.01409. Epub 2024 Feb 29. PMID: 38422473.Tripathy D, et al. Treatment with etirinotecan pegol for patients with metastatic breast cancer and brain metastases: final results from the Phase 3 ATTAIN randomized clinical trial. JAMA Oncol. 2022;8(7):1047-1052. doi:10.1001/jamaoncol.2022.0514.O'Shaughnessy J et al. Analysis of patients without and with an initial triple-negative breast cancer diagnosis in the Phase 3 randomized ASCENT study of sacituzumab govitecan in metastatic triple-negative breast cancer. Breast Cancer Res Treat. 2022 Sep;195(2):127-139. doi: 10.1007/s10549-022-06602-7. Epub 2022 May 11. PMID: 35545724; PMCID: PMC9374646. About BriaCell Therapeutics Corp. BriaCell is a clinical-stage biotechnology company that develops novel immunotherapies to transform cancer care. More information is available at https://briacell.com/. Safe Harbor This press release contains “forward-looking statements” that are subject to substantial risks and uncertainties. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. Forward-looking statements contained in this press release may be identified by the use of words such as “anticipate,” “believe,” “contemplate,” “could,” “estimate,” “expect,” “intend,” “seek,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “target,” “aim,” “should,” “will,” “would,” or the negative of these words or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements, including those about the presentation at the 2024 ASCO of two poster sessions, one abstract, and the delivery of an oral presentation by Dr. Saranya Chumsri, and the contents of all such materials and presentations; BriaCell's novel immunotherapy offering a well-tolerated treatment option for patients beyond the currently approved drugs; Bria-IMT™ having the potential to become a breakthrough novel treatment option for patients in advanced metastatic breast cancer; “Treatment of Physician’s Choice” (TPC) being the comparator in the Phase 3 study of Bria-IMT™; monotherapy becoming another arm of the Bria-IMT™ regimen; the potential clinical benefit of Bria-IMT™ in managing CNS metastases disease in advanced breast cancer; BriaCell continuing to monitor the data in the intracranial disease subgroup of patients in its ongoing pivotal Phase 3 study in advanced metastatic breast cancer; and the treatment of patients with CNS metastatic disease representing a potential additional indication for market approval of Bria-IMT™, are based on BriaCell’s current expectations and are subject to inherent uncertainties, risks, and assumptions that are difficult to predict. Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. These and other risks and uncertainties are described more fully under the heading “Risks and Uncertainties” in the Company’s most recent Management’s Discussion and Analysis, under the heading “Risk Factors” in the Company’s most recent Annual Information Form, and under “Risks and Uncertainties” in the Company's other filings with the Canadian securities regulatory authorities and the U.S. Securities and Exchange Commission, all of which are available under the Company's profiles on SEDAR+ at www.sedarplus.ca and on EDGAR at www.sec.gov. Forward-looking statements contained in this announcement are made as of this date, and BriaCell Therapeutics Corp. undertakes no duty to update such information except as required under applicable law. Neither the Toronto Stock Exchange nor its Regulation Services Provider (as that term is defined in the policies of the Toronto Stock Exchange) accepts responsibility for the adequacy or accuracy of this release. Contact Information Company Contact:William V. Williams, MDPresident & CEO1-888-485-6340info@briacell.com Media Relations:Jules AbrahamCORE IRjulesa@coreir.com Investor Relations Contact:CORE IRinvestors@briacell.com Photos accompanying this announcement are available at https://www.globenewswire.com/NewsRoom/AttachmentNg/6fff10ca-4660-4c6f-bb46-719f0f21887dhttps://www.globenewswire.com/NewsRoom/AttachmentNg/2b7cbddb-da76-486d-b6c3-22894a42933ahttps://www.globenewswire.com/NewsRoom/AttachmentNg/66f03119-a4b3-4d2d-a998-ab355aefdeac

关注并星标CPHI制药在线胰腺癌，号称癌王，2020 年全球约有 49.6 万人被确诊为胰腺导管腺癌，是导致癌症相关死亡的第七大原因。因发病隐匿，容易复发转移，早期症状不明显，许多患者发现确诊时已是晚期，无法手术治疗，大部分患者存在转移性病灶，导致临床治疗效果及预后极差，患者5年生存率（<8%），远低于其他恶性肿瘤。由于早期发现和治疗策略没有真正改善，预计到 2040 年，胰腺导管腺癌将成为西方国家癌症相关死亡的第二大原因。       胰腺癌治疗手段不外乎手术切除、化学治疗（化疗）、放射治疗（放疗）和介入治疗等。其中化疗是复发或转移性胰腺癌的治疗基石，但药物进展缓慢。以吉西他滨为基础的治疗方案是目前胰腺癌一线治疗的标准方案。新近的脂质体伊立替康的开发与上市为胰腺癌的治疗提供了新选择。脂质体伊立替康是第一个被FDA批准用于治疗前期接受过基于吉西他滨化疗方案的转移性胰腺癌的药物，在美国由 IPSEN 公司生产，在欧洲市场由 SERVIER 公司生产，是唯一一种在多项大型随机对照试验中证明可改善晚期胰腺导管癌患者生存率的药物。       脂质体伊立替康将伊立替康以活性内酯结构包封于脂质体中，避免被过早激活或失活，给药24h后体内仍能检测到23.2%的脂质体伊立替康，且并未转化为SN-38或羧酸盐形式，脂质体伊立替康可以促使肿瘤血管正常化和改善肿瘤组织缺氧微环境。全球多中心Ⅲ期临床试验研究（NAPOLI-1），探讨了脂质体伊立替康联合5-FU/亚叶酸方案在以吉西他滨为基础的方案治疗后进展的转移性胰腺癌患者的疗效。研究表明，脂质体伊立替康单药治疗组的生存优势与5-FU/亚叶酸治疗组无显著差异；但脂质体伊立替康与5-FU/亚叶酸联合用药组较5-FU/亚叶酸组具有显著的生存优势，中位OS分别为6.1个月和4.2个月，中位PFS分别为3.1个月和1.5个月，ORR分别为16%和1%。       2022年11月9日，Ipsen宣布胰腺癌一线治疗NALIRIFOX方案（Onivyde+5-氟尿嘧啶/亚叶酸+奥沙利铂）的III期NAPOLI 3研究。这是一项多中心、随机、开放标签的III期临床试验，共纳入770例患者，旨在评估NALIRIFOX方案对比白蛋白结合型紫杉醇+吉西他滨治疗初诊初治的转移性胰腺导管腺癌（mPDAC）患者的疗效和安全性。NALIRIFOX 还被纳入了最新的美国国家综合癌症网络指南，列为治疗不可切除的胰腺导管腺癌的推荐方案之一。将脂质体伊立替康纳入一线治疗的临床实验是NAPOLI 3试验，最初的 I/II 期试验评估了其安全性和有效性，最初脂质体伊立替康剂量为 70 毫克/平方米，奥沙利铂的剂量为 60 毫克/平方米。由于骨髓毒性随后的MTD 确定为50mg/m2的脂质体伊立替康和60mg/m2的奥沙利铂，NALIRIFOX具有可控的安全性和良好的活性，奥沙利铂的推荐剂量在NALIRIFOX 的推荐剂量（60 mg/m2）低于 FOLFIRINOX 方案中使用的剂量（85 mg/m2）。中位 PFS 和 OS 分别为 9.2 个月（95% CI：7.69-11.96）和 12.6 个月（8.74-18.69）。NAPOLI3 试验的意向治疗人群包括来自全球 19 个国家的 770 名患者。入组患者中 约 31% 来自北美，3% 来自亚洲，66% 来自东欧和西欧、南美洲和澳大利亚。两组患者的基线特征非常均衡，其中NALIFIROX 组 Ca199升高的患者比例略高，在 OS 数据分析中中位随访期为 16.1 个月，NALIRIFOX 组中位OS11.1个月（95% CI 10.0-12.1） 明显高于       白蛋白-紫杉醇加吉西他滨组的中位OS（9.2个月）。同样，NALIFIROX 组的中位 PFS 更长，为 7.4 个月，而白蛋白结合型-紫杉醇加吉西他滨组的中位 PFS 为 5.6 个月。NALIFIROX或白蛋白紫杉醇加吉西他滨组12个月和18个月的PFS率分别为 27.4%、13.9% 和 11.4%、3.6%。这项结果支持将 NALIRIFOX 方案作为一线治疗的潜在新标准。 在 NAPOLI3 试验中，NALIRIFOX 的安全性是可控的，并且与单个疗法的安全性一致。在决定使用FOLFIRINOX 和白蛋白-紫杉醇加吉西他滨哪一种作为一线疗法时，需要考虑基因突变、病人状态、年龄和潜在的合并症等因素。还要考虑药物毒性的影响，两药联合治疗比三药联合治疗更安全。脂质体伊立替康在传统伊立替康不耐受的情况下显示出显著优势，最近已经获得美国和欧洲药品机构的批准，NALIRIFOX 有可能成为转移性胰腺导管腺癌患者治疗方案中新的希望。       参考文献：       1. Buckley CW, O'Reilly EM. Next-generation therapies for pancreatic cancer. Expert Rev Gastroenterol Hepatol. 2024 Jan-Feb;18(1-3):55-72.       2.米秀芳,丁海樱,宋俞,等. 脂质体伊立替康治疗转移性胰腺癌临床研究进展[J]. 中国药业,2023,32(1):124-128. DOI:10.3969/j.issn.1006-4931.2023.01.030.来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~