Camonsertib

CAMBRIDGE, MA, USA & MONTREAL, Canada I October 14, 2024 I Repare Therapeutics Inc. (“Repare” or the “Company”) (Nasdaq: RPTX), a leading clinical-stage precision oncology company, today announced the first patient has been dosed in the Company’s Phase 1 (POLAR) clinical trial evaluating RP-3467, a Polθ ATPase inhibitor, alone and in combination with the poly-ADP ribose polymerase (PARP) inhibitor, olaparib. RP-3467 is Repare’s fourth clinical program. “RP-3467, our potential best-in-class Polθ ATPase inhibitor, has demonstrated highly compelling preclinical results, including complete and durable tumor regressions in combination with olaparib, the leading PARP inhibitor, with no additive toxicities. This combination is designed to meaningfully improve patient outcomes by mitigating PARP inhibitor resistance, a significant area of high unmet medical need,” said Maria Koehler, MD, PhD, Executive Vice President and Chief Medical Officer of Repare. “In addition, Repare’s previously reported data established the potential for RP-3467 to improve efficacy and limit toxicity in combination with radioligand therapy and chemotherapy-bearing antibody drug conjugates (ADCs), and we look forward to exploring those areas.” The POLAR clinical trial ( NCT06560632 ) is a multicenter, open-label, dose-escalation Phase 1 clinical trial to investigate the safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of RP-3467 alone or in combination with the PARP inhibitor, olaparib, in adults with molecularly selected advanced solid tumors. The study is expected to enroll approximately 52 patients with locally advanced or metastatic epithelial ovarian cancer, metastatic breast cancer, metastatic castration-resistant prostate cancer, or pancreatic adenocarcinoma. The primary objectives of the study are to assess the safety and tolerability of RP-3467 alone and in combination with olaparib, and to define a preliminary recommended Phase 2 dose of RP-3467 in combination with olaparib. About Repare Therapeutics, Inc. Repare Therapeutics is a leading clinical-stage precision oncology company enabled by its proprietary synthetic lethality approach to the discovery and development of novel therapeutics. The Company utilizes its genome-wide, CRISPR-enabled SNIPRx® platform to systematically discover and develop highly targeted cancer therapies focused on genomic instability, including DNA damage repair. The Company’s pipeline includes lunresertib (also known as RP-6306), a PKMYT1 inhibitor currently in Phase 1/2 clinical development; camonsertib (also known as RP-3500), a potential leading ATR inhibitor currently in Phase 1/2 clinical development; RP-1664, a Phase 1 PLK4 inhibitor; RP-3467, a Phase 1 Polθ ATPase inhibitor; as well as additional, undisclosed preclinical programs. For more information, please visit reparerx.com and follow @Reparerx on X (formerly Twitter) and LinkedIn. SOURCE: Repare Therapeutics

▎药明康德内容团队编辑 本期看点 1. T细胞受体T细胞（TCR-T）疗法IMA203在一项1b期临床试验中令92%转移性黑色素瘤患者的疾病获得控制，且患者的中位缓解持续时间（DOR）超过一年。 2. B细胞成熟抗原（BCMA）靶向自体嵌合抗原受体（CAR）-T细胞疗法Ribrecabtagene autoleucel（DRL-1801）用于治疗复发/难治性多发性骨髓瘤患者的1期临床试验结果亮眼，首批8名接受治疗的患者均获得了临床缓解。 3. 用于治疗胶质母细胞瘤（GBM）的树突状细胞疫苗DOC1021相比于标准治疗（SOC）有望大幅延长患者的中位总生存期（OS）。 药明康德内容团队整理 IMA203：公布1b期临床试验数据 Immatics公布了其在研TCR-T疗法IMA203用以治疗转移性黑色素瘤患者的最新1b期临床数据，这些患者先前接受过大量治疗。IMA203是由Immatics专有的ACTengine平台所开发的TCR-T细胞疗法，靶向由HLA-A*02呈递的黑素瘤抗原PRAME。PRAME是一种在各种实体瘤中经常表达的蛋白质，因此IMA203具潜力治疗广泛的癌症患者群体。 此次公布的结果显示，92%患者的疾病获得控制且患者的中位DOR超过一年。根据此积极数据，Immatics预定在今年12月启动SUPRAME注册性3期试验，预计病患招募将于2026年完成，并在2026年初进行预定的中期分析。 Ribrecabtagene autoleucel（DRL-1801）：公布1期临床试验数据 Aurigene Oncology公司宣布其新型BCMA靶向自体CAR-T细胞疗法Ribrecabtagene autoleucel（DRL-1801）用于治疗复发/难治性多发性骨髓瘤的1期临床试验中首批8名患者的初步结果。所有患者都接受过大量的前期治疗，中位治疗线数为5.5线。大多数患者此前也曾接受过移植手术，并在移植后出现疾病进展。结果显示，100%的患者获得了临床缓解，其中有5名（62.5%）患者获得了严格的完全缓解（CR）。安全性方面，所有患者均未出现高级别的细胞因子释放综合征（CRS）或神经毒性。 DOC1021：公布1期临床试验的中期数据 Diakonos Oncology公司公布了其树突状细胞疫苗DOC1021用于治疗胶质母细胞瘤患者的1期开放标签试验的中期分析结果。该公司的树突状细胞疫苗由患者自身的免疫细胞与从肿瘤样本中提取的RNA和蛋白质结合制成。这种独特的方法可以靶向完整的癌症抗原谱，而无需进行任何基因修饰。通过利用天然的免疫信号通路，这种策略使免疫系统能将癌细胞视同受病毒感染的细胞一样进行识别和清除。 此次公布的结果显示，15例患有挑战性肿瘤、MGMT未甲基化（通常预后不良）患者中有14例存活超过12个月。目前，中位随访时间为16个月，中位OS尚未达到。Kaplan-Meier（KM）分析将接受DOC1021治疗的患者与接受完整SOC的年龄匹配历史对照组患者进行比较，两组在统计学上具有差异（p=0.03）。KM预测接受DOC1021治疗的患者的OS为19.7个月，而接受SOC的未甲基化GBM患者的预期OS为12.7个月。安全性方面，没有剂量限制性毒性或令人担忧的严重不良事件（SAE）。 VIP943：公布1期临床试验数据 Vincerx Pharma公司公布了其抗体偶联药物（ADC）VIP943治疗复发/难治性急性髓系白血病（AML）、高危骨髓增生异常综合征（HR-MDS）和B细胞急性淋巴细胞白血病（B-ALL）的1期临床试验的结果。VIP943由抗CD123抗体、一种在细胞内切割的独特连接子和一种新型驱动蛋白纺锤体蛋白抑制剂（KSPi）有效载荷组成。Vincerx的CellTrapper技术可确保KSPi有效载荷积聚在靶细胞中，限制非靶细胞、非分裂细胞的吸收，从而减少非特异性释放。 该1期剂量递增研究共招募了22名患者，他们很少对单一疗法产生应答。9名患者（6名AML患者和3名HR-MDS患者）至少接受了3次有效剂量的VIP943治疗。截至目前，1名复发性AML患者获得了完全缓解伴血液学不完全恢复（CRi），1名HR-MDS患者获得了完全缓解伴较少血液学恢复（CRL）。截至2024年8月的数据，VIP943显示出良好的安全性和耐受性，没有报告剂量限制性毒性，SAE与预期一致。 VK0214：公布1b期临床试验数据 Viking Therapeutics公司公布了其新型甲状腺激素受体β（TRβ）小分子激动剂VK0214在X-连锁肾上腺白质营养不良（X-ALD）患者中进行的1b期临床试验的积极数据。X-ALD是一种罕见的致命代谢性疾病，由ABCD1基因突变引起，这种突变会导致肾上腺脑白质营养不良蛋白（ALDP）功能障碍，从而引起脂肪酸的异常累积。临床前研究表明，甲状腺激素受体β型可以调节ABCD2相关基因的表达，ABCD2能够编码一种称为肾上腺脑白质营养不良相关蛋白（ADLRP）的代偿转运体，通过增加ABCD2表达可以使特定脂肪酸水平恢复正常。 此次公布的研究结果表明，在为期28天的研究期间，VK0214每天用药一次的安全性和耐受性良好。此外，与安慰剂相比，接受VK0214治疗患者血浆中的超长链脂肪酸（VLCFAs）和其他血脂水平明显降低。 ▲VK0214治疗28天后患者的VLCFA与基线相比的变化（图片来源：参考资料[5]） ▲VK0214治疗28天后患者的其他血脂与基线相比的变化（图片来源：参考资料[5]） Paxalisib：公布1期临床试验的新数据 Kazia Therapeutics公司公布其口服PI3K/mTOR双抑制剂paxalisib联用放射疗法治疗PI3K通路突变实体瘤脑转移（BM）或软脑膜转移（LM）患者的1期临床试验的数据。此次公布的结果显示，paxalisib联用放疗总体耐受性良好。研究中最常报告的不良反应是恶心、呕吐和高血糖。接受45 mg paxalisib联用放疗患者中有67%获得了部分缓解（PR），接受最大耐受剂量治疗的患者中有超过三分之二的人获得了颅内缓解，这与单独使用全脑放疗的历史缓解率相比毫不逊色。 ELVN-001：公布1期临床试验的新数据 Enliven Therapeutics公司公布其小分子激酶抑制剂ELVN-001治疗复发/难治性或对现有酪氨酸激酶抑制剂（TKI）不耐受的慢性髓系白血病（CML）患者的1期临床试验的积极数据。ELVN-001是一种强效、高选择性、潜在“best-in-class”的小分子激酶抑制剂，专门针对CML患者的致癌驱动因子BCR-ABL融合蛋白。ELVN-001还具有针对耐药性最强的BCR-ABL1耐药突变体T315I和其他已知耐药突变体的活性。 截至2024年6月25日的数据，ELVN-001的耐受性保持良好，没有患者减少剂量，未报告≥3级治疗相关的非血液学毒性反应。第24周时，患者的初始累积主要分子缓解（MMR）率为44%（8/18），与已获批的BCR-ABL1酪氨酸激酶抑制剂在1期临床试验中的数据相比具有优势。 Camonsertib：公布1期联合治疗试验数据 Repare Therapeutics公司公布了潜在”best-in-class”口服小分子ATR抑制剂camonsertib结合姑息性放疗，治疗携带ATM突变转移性肿瘤的1期临床试验数据。该试验纳入了17例携带ATM突变的转移性肿瘤患者，其中12人携带致病性ATM基因突变，5人携带ATM基因突变的意义不明变异（VUS）。这些患者的原发性癌症组织学来源包括胃肠道（n=5）、胰腺（n=5）、乳腺癌（n=2）、肺（n=2）、膀胱（n=2）和甲状腺（n=1）。 此次公布的结果显示，2个月时，致病性ATM突变组有2例CR、5例PR和4例疾病稳定（SD）患者，而VUS组有1例PR和4例SD患者。6个月时，在9名可评估患者中，致病性ATM突变组有2例CR、4例PR和1例SD患者，而VUS组有1例SD和1例疾病进展患者。该早期临床数据表明camonsertib联合放疗治疗有可能对携带致病性ATM突变的肿瘤患者进行放射增敏，从而获得更高的临床益处。 Misetionamide：公布1期临床试验的中期数据 Panavance Therapeutics公司公布了其小分子疗法misetionamide（GP-2250）联用吉西他滨治疗晚期不可切除或转移性胰腺导管腺癌患者1期临床试验的中期数据。Misetionamide具有独特的作用机制，可抑制两种致癌转录因子c-MYC和NFκB。此次公布的结果显示，与单独使用吉西他滨的历史结果相比，接受misetionamide联用吉西他滨治疗患者的无进展生存期更长，约40%的患者达到PR或SD。此外，misetionamide联用吉西他滨的安全性良好。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放 参考资料（可上下滑动查看） [1] Vincerx Reports Positive Initial Clinical Data from Ongoing VIP943 Phase 1 Dose-Escalation Study and Provides Pipeline and Corporate Updates. Retrieved October 11, 2024, from https://www.globenewswire.com/news-release/2024/10/07/2959307/0/en/Vincerx-Reports-Positive-Initial-Clinical-Data-from-Ongoing-VIP943-Phase-1-Dose-Escalation-Study-and-Provides-Pipeline-and-Corporate-Updates.html [2] CNS 2024 Conference Presentation: Diakonos Oncology’s Autologous Dendritic Cell Vaccine (DOC1021) Yields 93% 12-Month Survival for Glioblastoma Patients. Retrieved October 11, 2024, from https://www.diakonosoncology.com/news/cns-2024-conference-presentation-diakonos-oncologys-autologous-dendritic-cell-vaccine-doc1021-yields-93-12-month-survival-for-glioblastoma-patients/ [3] Enliven Therapeutics Announces Positive Data Update from Phase 1 Clinical Trial of ELVN-001 in Chronic Myeloid Leukemia. Retrieved October 11, 2024, from https://www.globenewswire.com/news-release/2024/09/28/2954762/0/en/Enliven-Therapeutics-Announces-Positive-Data-Update-from-Phase-1-Clinical-Trial-of-ELVN-001-in-Chronic-Myeloid-Leukemia.html [4] Kazia Therapeutics Announces Presentation of Promising Phase I Data Evaluating Concurrent Paxalisib and Radiation Therapy in Patients with Solid Tumor Brain Metastases or Leptomeningeal Metastases Harboring PI3K Pathway Mutations at the American Society for Radiation Oncology 66th Annual Meeting. Retrieved October 11, 2024, from https://www.prnewswire.com/news-releases/kazia-therapeutics-announces-presentation-of-promising-phase-i-data-evaluating-concurrent-paxalisib-and-radiation-therapy-in-patients-with-solid-tumor-brain-metastases-or-leptomeningeal-metastases-harboring-pi3k-pathway-mutations--302265538.html [5] Viking Therapeutics Announces Results from Phase 1b Clinical Trial of VK0214 in Patients with X-ALD. Retrieved October 11, 2024, from https://www.prnewswire.com/news-releases/viking-therapeutics-announces-results-from-phase-1b-clinical-trial-of-vk0214-in-patients-with-x-ald-302270769.html [6] Repare Therapeutics Announces Phase 1 Data Highlighting Camonsertib in Combination with Radiotherapy Treatment Presented at the ASTRO Annual Meeting. Retrieved October 11, 2024, from https://ir.reparerx.com/news-releases/news-release-details/repare-therapeutics-announces-phase-1-data-highlighting [7] Panavance Therapeutics Provides Update on Phase 1 Clinical Trial of Misetionamide in Pancreatic Cancer at 2024 Visceral Medicine Congress. Retrieved October 11, 2024, from https://www.globenewswire.com/news-release/2024/10/09/2960394/0/en/Panavance-Therapeutics-Provides-Update-on-Phase-1-Clinical-Trial-of-Misetionamide-in-Pancreatic-Cancer-at-2024-Visceral-Medicine-Congress.html [8] Aurigene Oncology Limited Announces Promising Results of Phase 1 Study for India’s First Trial for Novel Autologous CAR-T Cell Therapy for Multiple Myeloma. Retrieved October 11, 2024, from https://www.businesswire.com/news/home/20241008755325/en/Aurigene-Oncology-Limited-Announces-Promising-Results-of-Phase-1-Study-for-India%E2%80%99s-First-Trial-for-Novel-Autologous-CAR-T-Cell-Therapy-for-Multiple-Myeloma/ [9] Immatics Announces Updated Phase 1b Clinical Data on ACTengine® IMA203 TCR-T Targeting PRAME in Melanoma Patients and Provides Update on Upcoming SUPRAME Phase 3 Trial. Retrieved October 10, 2024 from https://www.globenewswire.com/news-release/2024/10/10/2961129/0/en/Immatics-Announces-Updated-Phase-1b-Clinical-Data-on-ACTengine-IMA203-TCR-T-Targeting-PRAME-in-Melanoma-Patients-and-Provides-Update-on-Upcoming-SUPRAME-Phase-3-Trial.html [10] BlueRock Therapeutics’ investigational cell therapy bemdaneprocel for Parkinson’s disease shows positive data at 24-months. Retrieved October 11, 2024, from https://www.bayer.com/en/us/cell-therapy-bemdaneprocel [11] Estrella Immunopharma Achieves Complete Response in First Patient Treated with CD19- Redirected ARTEMIS® T-cells. Retrieved October 11, 2024, from https://www.estrellabio.com/news/estrella-immunopharma-achieves-complete-response-in-first-patient-treated-with-cd19--redirected-artemis%C2%AE-t-cells [12] INKmune Demonstrates Excellent Safety and Increased NK-Cell Activity in First Dosing Cohort. Retrieved October 11, 2024, from https://inmunebio.com/index.php/newsroom/2024-news/muneemonstratesxcellentafetyandncreasede20240926050502 [13] Theriva Biologics Announces Positive Outcome of Data and Safety Monitoring Committee (DSMC) Review in Phase 1b/2a Clinical Trial of SYN-004 (ribaxamase) in Allogeneic Hematopoietic Cell Transplant Recipients. Retrieved October 11, 2024, from https://www.globenewswire.com/news-release/2024/10/03/2957647/0/en/Theriva-Biologics-Announces-Positive-Outcome-of-Data-and-Safety-Monitoring-Committee-DSMC-Review-in-Phase-1b-2a-Clinical-Trial-of-SYN-004-ribaxamase-in-Allogeneic-Hematopoietic-Cel.html [14] Alentis Therapeutics Receives FDA IND Clearance for ALE.P02, a Novel CLDN1-ADC for the Treatment of Squamous Cancers. Retrieved October 11, 2024, from https://pipelinereview.com/alentis-therapeutics-receives-fda-ind-clearance-for-ale-p02-a-novel-cldn1-adc-for-the-treatment-of-squamous-cancers/ [15] NeuroBo Pharmaceuticals Announces Positive Top-Line Data From the SAD Part 1 of Its Phase 1 Clinical Trial Evaluating DA-1726 for the Treatment of Obesity. Retrieved October 11, 2024, from https://www.prnewswire.com/news-releases/neurobo-pharmaceuticals-announces-positive-top-line-data-from-the-sad-part-1-of-its-phase-1-clinical-trial-evaluating-da-1726-for-the-treatment-of-obesity-302261698.html [16] Calidi Biotherapeutics Announces FDA Clearance of the Northwestern University IND Application for CLD-101 Clinical Trial in High-Grade Glioma. Retrieved October 11, 2024, from https://www.globenewswire.com/news-release/2024/09/30/2955149/0/en/Calidi-Biotherapeutics-Announces-FDA-Clearance-of-the-Northwestern-University-IND-Application-for-CLD-101-Clinical-Trial-in-High-Grade-Glioma.html [17] Adcendo Announces US FDA Clearance of IND Application for Phase I/II First-in-Human ADCElerate-01 Trial of ADCE-D01 (uPARAP Receptor Targeting ADC) Trial in Patients With Metastatic and/or Unresectable Soft Tissue Sarcoma (STS). Retrieved October 11, 2024, from https://pipelinereview.com/adcendo-announces-us-fda-clearance-of-ind-application-for-phase-i-ii-first-in-human-adcelerate-01-trial-of-adce-d01-uparap-receptor-targeting-adc-trial-in-patients-with-metastatic-and-or-unresectabl/ [18] Safety and immunogenicity of CD40.HIVRI.Env, a dendritic cell-based HIV vaccine, in healthy HIV-uninfected adults: a first-in-human randomized, placebo-controlled, dose-escalation study (ANRS VRI06). Retrieved October 11, 2024, from https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00424-3/fulltext [19] Myrtelle Announces Significant Reduction in N-Acetylaspartate (NAA), a Key Biomarker, in Patients Treated in Its Phase 1/2 Clinical Trial of the Investigational Gene Therapy rAAV-Olig001-ASPA for Canavan Disease. Retrieved October 11, 2024, from https://www.prnewswire.com/news-releases/myrtelle-announces-significant-reduction-in-n-acetylaspartate-naa-a-key-biomarker-in-patients-treated-in-its-phase-12-clinical-trial-of-the-investigational-gene-therapy-raav-olig001-aspa-for-canavan-disease-302263264.html [20] Kiromic BioPharma Reports Favorable 10-Month Follow-Up Results for the First Patient Treated in its Deltacel-01 Clinical Trial. Retrieved October 11, 2024, from https://www.businesswire.com/news/home/20241001186898/en/Kiromic-BioPharma-Reports-Favorable-10-Month-Follow-Up-Results-for-the-First-Patient-Treated-in-its-Deltacel-01-Clinical-Trial [21] Recursion Announces FDA Clearance of Investigational New Drug Application for REC-1245, a Potential First-In-Class RBM39 Degrader for Biomarker-Enriched Solid Tumors and Lymphoma. Retrieved October 11, 2024, from https://www.globenewswire.com/news-release/2024/10/02/2956875/0/en/Recursion-Announces-FDA-Clearance-of-Investigational-New-Drug-Application-for-REC-1245-a-Potential-First-In-Class-RBM39-Degrader-for-Biomarker-Enriched-Solid-Tumors-and-Lymphoma.html [22] Kymera Therapeutics Announces FDA Clearance of Investigational New Drug Application for KT-621, a First-in-Class, Oral STAT6 Degrader. Retrieved October 11, 2024, from https://investors.kymeratx.com/news-releases/news-release-details/kymera-therapeutics-announces-fda-clearance-investigational-0 [23] Vanqua Bio Announces Positive Interim Results from Phase 1 Clinical Trial of VQ-101, an Orally Administered, Brain-Penetrant, Allosteric Activator of GCase for the Treatment of GBA-Parkinson’s and Related Disorders. Retrieved October 11, 2024, from https://www.globenewswire.com/news-release/2024/10/09/2960411/0/en/Vanqua-Bio-Announces-Positive-Interim-Results-from-Phase-1-Clinical-Trial-of-VQ-101-an-Orally-Administered-Brain-Penetrant-Allosteric-Activator-of-GCase-for-the-Treatment-of-GBA-Pa.html [24] Traws Pharma Announces Positive Topline Phase 1 Data for Flu Candidate, Tivoxavir Marboxil. Retrieved October 11, 2024, from https://www.globenewswire.com/news-release/2024/10/08/2959584/0/en/Traws-Pharma-Announces-Positive-Topline-Phase-1-Data-for-Flu-Candidate-Tivoxavir-Marboxil.html [25] Gain Therapeutics Presents Phase 1 GT-02287 Data at International Congress of Parkinson’s Disease and Movement Disorders Demonstrating Increase in GCase Activity in Healthy Volunteers. Retrieved October 11, 2024, from https://www.globenewswire.com/news-release/2024/09/30/2955049/0/en/Gain-Therapeutics-Presents-Phase-1-GT-02287-Data-at-International-Congress-of-Parkinson-s-Disease-and-Movement-Disorders-Demonstrating-Increase-in-GCase-Activity-in-Healthy-Volunte.html [26] Kura Oncology Announces Publication of Ziftomenib Phase 1 Results in The Lancet Oncology. Retrieved October 11, 2024, from https://www.globenewswire.com/news-release/2024/09/30/2955703/35186/en/Kura-Oncology-Announces-Publication-of-Ziftomenib-Phase-1-Results-in-The-Lancet-Oncology.html [27] Allakos Announces Phase 1 Trial Results of Subcutaneous AK006 in Healthy Volunteers. Retrieved October 11, 2024, from https://investor.allakos.com/news-releases/news-release-details/allakos-announces-phase-1-trial-results-subcutaneous-ak006 [28] Ultragenyx Provides Update on Stage 1 Cohorts in Pivotal Phase 1/2/3 Cyprus2+ Study Evaluating UX701 Gene Therapy for the Treatment of Wilson Disease. Retrieved October 4, 2024, from https://www.globenewswire.com/news-release/2024/10/03/2958032/0/en/Ultragenyx-Provides-Update-on-Stage-1-Cohorts-in-Pivotal-Phase-1-2-3-Cyprus2-Study-Evaluating-UX701-Gene-Therapy-for-the-Treatment-of-Wilson-Disease.html 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新