Valrubicin

Patient Reported Outcomes (PROs) based on a May 16, 2022 data cutoff in the QUILT 3.032 trial indicate stability of physical function and global health in patients who completed PRO questionnaires and reached month 24 on-study Overall, participants with complete responses (CRs) to combination therapy with the novel interleukin-15 (IL-15) superagonist N-803 and bacillus Calmette-Guerin (BCG) reported better physical function than those who did not achieve a CR at month 6 Stability of these PROs supports the safety and tolerability of the potential new treatment combination Taken together with the positive durable 71% response and 89.2% cystectomy avoidance rates in cohort A and a favorable safety pro the May 16, 2022 data cutoff, along with the available PROs, support a favorable risk-benefit ratio for N-803 plus BCG in this patient population The Food and Drug Administration (FDA) is currently reviewing the Biologics License Application (BLA) for N-803 plus BCG for the treatment of NMIBC CIS with a Prescription Drug User Fee Act (PDUFA) date of April 23, 2024 CULVER CITY, Calif.--(BUSINESS WIRE)-- ImmunityBio, Inc. (NASDAQ: IBRX), a clinical-stage immunotherapy company, today announced that findings from Patient-Reported Outcomes (PROs) of participants in the phase 2/3 QUILT 3.032 study of N-803 plus BCG in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) were published by the peer-reviewed journal Urology Practice. These PROs support the positive interim results from the study published in NEJM Evidence, wherein 71% of patients in cohort A with CIS with or without Ta/T1 disease achieved a complete response. The published PROs based on a May 16, 2022 data cutoff indicate that both physical function and global health as self-reported by QUILT 3.032 participants with BCG-unresponsive NMIBC CIS (cohort A) or papillary disease (cohort B), remained stable over the 2-year course of the study for patients who completed the PRO questionnaires and reached 24 months on-study. In addition, overall both cohort A and B participants who reached month 24 on-study and also completed an NMIBC-specific questionnaire focusing on the challenges of bladder cancer, also reported no decline of their health or urinary tract-related symptoms while in the study. Overall, participants who achieved a complete response with the novel combination therapy reported better physical function by month six of the study than those who did not achieve a complete response. “The self-reported stability of health and physical function over the course of the study by the participants reflect another aspect of safety and tolerability of this new combination therapy,” said Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer at ImmunityBio. “Taken together with the positive response rate in cohort A of over 70%, the persistence of responses and cystectomy avoidance, these QoL findings suggest a favorable risk-benefit ratio for this potential new therapeutic option for patients with BCG-unresponsive bladder cancer.” The finding of relative stability of global health and physical function during the course of the study is similar to that reported by others for BCG monotherapy, suggesting the novel combination is as tolerable as treatment with BCG alone. “Many current therapies for bladder cancer slow disease progression but can cause debilitating side effects,” said Principal Investigator Karim Chamie, M.D., Associate Professor of Urology at UCLA. “The data from the QUILT 3.032 Quality of Life study suggest that many patients not only have a durable response but also report no decline in physical function, which is very important for these patients.” QUILT 3.032 Study Details The ongoing phase 2/3 open-label multicenter registrational study QUILT 3.032 (NCT03022825) is evaluating the safety and efficacy of the investigational interleukin-15 superagonist N-803 (also known as Anktiva® and nogapendekin alfa inbakicept, NAI) in combination with a standard therapy for NMIBC, bacillus Calmette-Guerin (BCG), in patients who failed or in whom cancer returned after BCG monotherapy, and thus were diagnosed as BCG-unresponsive. The study comprises three cohorts, with cohort A enrolling patients with carcinoma in situ (CIS) with or without Ta/T1 disease and cohort B enrolling patients with high grade Ta/T1 papillary disease. Both cohorts A and B received combination N-803 plus BCG therapy. Cohort C patients, with CIS +/- Ta/T1 disease received N-803 monotherapy. The primary end point is the incidence of CR at the 3- or 6-month assessment visit for cohorts A and C, and the disease-free survival (DFS) rate at 12 months for cohort B. Durability, cystectomy avoidance, progression-free survival, disease-specific survival (DSS), and overall survival are secondary end points for cohort A. Cohort C was discontinued due to a low response rate with N-803 monotherapy, per study design. The FDA has accepted for review ImmunityBio’s resubmission of its biologics license application (BLA) for N-803 plus BCG for the treatment of BCG-unresponsive NMIBC CIS with or without Ta or T1 disease, and has set a user fee goal date (PDUFA date) of April 23, 2024. Bladder cancer is the 10th most-commonly diagnosed cancer, with approximately 80% of newly diagnosed cases being NMIBC. Intravesical (directly to the bladder) instillation of BCG after removal of cancer tissue from the lining of the bladder (transurethral resection of the bladder tumor; TURBT) is Standard-of-Care (SoC) for intermediate and high-risk NMIBC patients, but up to 40% of patients will fail BCG therapy and ~50% will relapse after an initial response and given a diagnosis of being BCG-unresponsive. Therapies approved by the FDA for this indication include pembrolizumab, nadofaragene, combined gemcitabine and docetaxel, and valrubicin. Radical cystectomy – surgical removal of the bladder - is also an option for these patients. QUILT 3.032 is being conducted to address the need for a safe, effective therapeutic option for BCG-unresponsive NMIBC patients that provides an opportunity for avoidance of radical cystectomy. N-803 is investigational. Safety and efficacy have not been established by any Health Authority or Agency, including the FDA. About ImmunityBio ImmunityBio is a vertically-integrated, clinical-stage biotechnology company developing next-generation therapies and vaccines that bolster the natural immune system to defeat cancers and infectious diseases. The Company’s range of immunotherapy and cell therapy platforms, alone and together, act to drive and sustain an immune response with the goal of creating durable and safe protection against disease. ImmunityBio is applying its science and platforms to treating cancers, including the development of potential cancer vaccines, as well as developing immunotherapies and cell therapies that ImmunityBio believes sharply reduce or eliminates the need for standard high-dose chemotherapy. These platforms and their associated product candidates are designed to be more effective, accessible, and easily administered than current standards of care in oncology and infectious diseases. For more information, please visit Immunitybio.com. 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More details about these and other risks that may impact ImmunityBio’s business are described under the heading “Risk Factors” in the Company’s Form 10-K filed with the U.S. Securities and Exchange Commission (“SEC”) on March 1, 2023 and the Company’s Form 10-Q filed with the SEC on November 9, 2023, and in subsequent filings made by ImmunityBio with the SEC, which are available on the SEC’s website at . ImmunityBio cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date hereof. ImmunityBio does not undertake any duty to update any forward-looking statement or other information in this press release, except to the extent required by law.

扫描文末二维码，申请药渡数据3天免费试用2022年7月28日，ImmunityBio宣布，FDA受理公司膀胱内卡介苗（BCG）联合新型IL-15超级激动剂复合物Anktiva（N-803）的BLA，进入审查阶段，该疗法用于治疗伴或不伴有Ta或T1疾病、对BCG无应答的非肌层浸润性膀胱癌(NMIBC)原位癌(CIS)。处方药使用者费用法案（PDUFA）的目标行动日期为2023年5月23日。N-803联用BCG是ImmunityBio第一个达到FDA受理审查阶段的BLA。 此次BLA递交是基于QUILT 3.032（NCT03022825）的研究结果，并且该试验的结果已在2022年美国临床肿瘤学会年会（ASCO 2022）上公布。QUILT 3.032是一项开放标签、三队列、多中心II/III期研究。结果显示，与FDA批准的Valrubicin和Pembrolizumab相比，N-803联用BCG疗法，有71% 既往治疗失败的患者在反应和中位持续时间方面均增加了50%以上，中位反应持续时间为26.6个月。在24个月时，应答者避免了96%的膀胱癌进展。此外，QUILT 3.032研究中，患者的膀胱切除术避免率为91%，膀胱癌在24个月时的总生存率为100%，并且严重不良反应事件（SAE）的发生率为0%。来源：药渡数据库   关于NMIBC根据国际癌症研究基金会统计，2020年大约有573,000例新确诊的膀胱癌患者，当年因膀胱癌死亡的患者大约有212,000。膀胱癌在世界范围内的发病率较高，而大约75-85%的膀胱癌存在局限于粘膜（Ta期，原位癌[CIS]）或粘膜下层（T1期）疾病，这些类别被归类为非肌肉浸润性膀胱癌（NMIBC），其中约70%为Ta期，20%为T1期，10%为CIS。大约90%的NMIBC病例为乳头状（Ta和T1期）。多年来，膀胱内BCG治疗一直是非侵袭性乳头状肿瘤患者的标准治疗方法，但不幸的是，无应答率在40%左右。 关于N-803白细胞介素-15（IL-15）通过影响自然杀伤（NK）和T细胞的发育，维持和功能在免疫系统中起着至关重要的作用。N-803是一种新型的IL-15超级激动剂复合物，由IL-15突变体（IL-15N72D）与IL-15受体α/IgG1 Fc融合蛋白结合而成。通过βγ-T细胞受体结合（非α）直接特异性激活CD8+T细胞和NK细胞，同时避免T-reg刺激。N-803具有独特的作用机制，可导致NK和T细胞的增殖。将N-803和BCG直接进行膀胱内灌注，通过N-803特有的作用机制，为卡介苗对膀胱癌产生的免疫反应或检查点抑制剂对其他适应症产生的免疫反应提供了二次增强。因此，N-803在体内具有优越的药代动力学性质，在淋巴组织中的持久性更长，抗肿瘤活性更强。来源：参考来源2根据药渡数据库不完全统计，N-803针对多种其他适应症正在开展临床研究。进展较快的还有针对非小细胞肺癌的临床研究，目前处于III期临床，另外N-803在国内正在进行针对血液系统疾病的II期临床研究。来源：药渡数据库 期待N-803联用BCG疗法的上市申请早日获批。一旦获批，它将成为将是23年来治疗NMIBC的第一个免疫疗法，也将极大地改善NMIBC患者目前的治疗困境。参考来源1.https://www.businesswire.com/2.ASCO 2022: Final Clinical Results of Pivotal Trial of IL-15RαFc Superagonist N-803 With BCG in BCG-Unresponsive CIS and Papillary Nonmuscle-Invasive Bladder Cancer (urotoday.com)3.药渡数据库4.Cancer Prevention Organisation | World Cancer Research Fund International - WCRF International扫描二维码，申请药渡数据免费试用