Pancreatic Ductal Adenocarcinoma

- Findings underscore that the combination of onvansertib with FOLFIRI and bevacizumab demonstrates clinical activity and is well tolerated in second-line KRAS-mutant mCRC - - Post hoc analysis resulted in a 7.7-fold higher clinical benefit in bev-naïve patients with an ORR of 77% compared to 10% in bev-exposed patients - - Results from this trial, along with translational studies, supported the transition of clinical development of onvansertib to first-line RAS-mutant mCRC - - Initial readout from first-line RAS-mutant mCRC CRDF-004 trial expected in H2 2024 - SAN DIEGO, Oct. 30, 2024 (GLOBE NEWSWIRE) -- Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, today announced the publication of data from our Phase 2 trial evaluating onvansertib in combination with FOLFIRI and bevacizumab (bev) for the second-line treatment of KRAS mutant metastatic colorectal cancer (mCRC) in the peer-reviewed Journal of Clinical Oncology, the flagship publication of the American Society of Clinical Oncology (ASCO). “It is exciting to see novel therapies in development that are well tolerated and demonstrate clinical activity in KRAS mutant mCRC, a cancer indication that has lacked new treatment options for decades,” said Heinz-Josef Lenz, MD, Professor of Medicine, J. Terrence Lanni Chair in Cancer Research, Deputy Cancer Center Director USC Norris Comprehensive Cancer Center, USC Keck School of Medicine and the national principal investigator on this trial. “The 77% objective response rate observed with onvansertib in combination with standard of care in bev-naïve patients is remarkable, and we look forward to determining the impact that onvansertib can make in the first-line setting.” “We are proud to be recognized by this prestigious oncology journal for our groundbreaking clinical and preclinical findings observed when adding onvansertib to the standard of care for KRAS mutant mCRC,” added Fairooz Kabbinavar, MD, FACP, Chief Medical Officer of Cardiff Oncology. We are highly encouraged by the clinical results demonstrating a 7.7x higher objective response rate (ORR) in patients who were not previously exposed to bev, and our subsequent discovery of a novel mechanism for onvansertib through our translational work. Collectively, these findings and the support of the FDA led us to shift our clinical development program for onvansertib to the first-line setting where all patients are bev-naïve.” The results of the published Phase 2 clinical trial treating patients with KRAS-mutant mCRC (NCT03829410) demonstrated that onvansertib combined with FOLFIRI and bev was well-tolerated and revealed a greater clinical benefit in bev-naïve patients (ORR of 77%, mPFS of 14.9 months) compared to bev-exposed patients (ORR of 10%, mPFS of 6.6 months). In addition, the company showed the underpinnings of this clinical finding using preclinical models which demonstrated onvansertib inhibited the hypoxia pathway and exhibited robust antitumor activity in combination with bev through the inhibition of angiogenesis. Based on these findings, Cardiff Oncology initiated CRDF-004, a Phase 2 randomized clinical trial of onvansertib in combination with SoC (FOLFIRI and bev or FOLFOX and bev) for the first-line treatment of patients with RAS mutant mCRC. The company anticipates releasing initial data from the CRDF-004 trial in the second half of 2024. About Cardiff Oncology, Inc. Cardiff Oncology is a clinical-stage biotechnology company leveraging PLK1 inhibition, a well-validated oncology drug target, to develop novel therapies across a range of cancers. The Company's lead asset is onvansertib, a PLK1 inhibitor being evaluated in combination with standard of care (SoC) therapeutics in clinical programs targeting indications such as RAS-mutated metastatic colorectal cancer (mCRC), as well as in ongoing and planned investigator-initiated trials in metastatic pancreatic ductal adenocarcinoma (mPDAC), small cell lung cancer (SCLC) and triple negative breast cancer (TNBC). These programs and the Company's broader development strategy are designed to target tumor vulnerabilities in order to overcome treatment resistance and deliver superior clinical benefit compared to SoC alone. For more information, please visit https://www.cardiffoncology.com. Forward-Looking Statements Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified using words such as "anticipate," "believe," "forecast," "estimated" and "intend" or other similar terms or expressions that concern Cardiff Oncology's expectations, strategy, plans or intentions. These forward-looking statements are based on Cardiff Oncology's current expectations and actual results could differ materially. There are several factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, clinical trials involve a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not be predictive of future trial results; our clinical trials may be suspended or discontinued due to unexpected side effects or other safety risks that could preclude approval of our product candidate; results of preclinical studies or clinical trials for our product candidate could be unfavorable or delayed; our need for additional financing; risks related to business interruptions, including the outbreak of an epidemic or pandemic such as the COVID-19 coronavirus and cyber-attacks on our information technology infrastructure, which could seriously harm our financial condition and increase our costs and expenses; uncertainties of government or third party payer reimbursement; dependence on key personnel; limited experience in marketing and sales; substantial competition; uncertainties of patent protection and litigation; dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. There are no guarantees that our product candidate will be utilized or prove to be commercially successful. Additionally, there are no guarantees that future clinical trials will be completed or successful or that our product candidate will receive regulatory approval for any indication or prove to be commercially successful. Investors should read the risk factors set forth in Cardiff Oncology's Form 10-K for the year ended December 31, 2023, and other periodic reports filed with the Securities and Exchange Commission. While the list of factors presented here is considered representative, no such list should be considered to be a complete statement of all potential risks and uncertainties. Unlisted factors may present significant additional obstacles to the realization of forward-looking statements. Forward-looking statements included herein are made as of the date hereof, and Cardiff Oncology does not undertake any obligation to update publicly such statements to reflect subsequent events or circumstances. Cardiff Oncology Contact:James LevineChief Financial Officer858-952-7670jlevine@cardiffoncology.com Investor Contact:Kiki Patel, PharmDGilmartin Group332-895-3225Kiki@gilmartinir.com Media Contact:Grace SpencerTaft Communications609-583-1151grace@taftcommunications.com

KRAS G12D是癌症中最常见的KRAS突变，在胰腺导管腺癌(PDAC)、结直肠癌(CRC)、非小细胞肺癌(NSCLC)中广泛存在，尤其在胰腺癌中较为常见，而且目前尚无针对这些患者的有效靶向疗法。 不过值得欣慰的是，近期美国一款针对KRAS G12D突变的抗癌新药，在治疗胰腺癌的早期临床研究中，获得了高达80%的疾病控制率，具有里程碑式的重大进展！ 一、新型KRAS G12D抑制剂——RMC-9805取得里程碑式进展，胰腺癌控制率高达80% RMC-9805是一款新型口服的 RAS(ON) G12D 选择性共价抑制剂，其在治疗实体瘤领域表现出令人鼓舞的抗肿瘤活性、初始安全性、耐受性。无论作为单一疗法还是联合疗法，RMC-9805在胰腺癌的治疗中，均展现出了惊艳的疗效。 RMC-9805治疗胰腺癌的1/1b 期 RMC-9805-001临床研究（NCT06040541），纳入存在KRAS G12D突变的局部晚期或转移性实体瘤，且既往接受过标准治疗的患者。截至数据截止，单药治疗组共有179例患者接受了递增剂量的 RMC-9805治疗。 结果显示，RMC-9805在 KRAS G12D 突变的胰腺导管腺癌（PDAC）患者中， 客观缓解率（ORR）达到 30% （n = 12）。 疾病控制率（DCR）更是高达80% （n = 32）， 这也意味着80%的胰腺癌患者，在接受RMC-9805治疗后，疾病得到有效控制 （详见下图）！ ▲图源“OneLive”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 二、案例分析 值得一提的是，一位70岁的KRAS G12D突变转移性胰腺癌女性患者，既往曾接受过放化疗、吉西他滨、紫杉醇等治疗，但效果不理想，患者伴肝转移、腹腔动脉及肠系膜上动脉受累，入组接受治疗RMC-9805治疗。 结果显示：ctDNA 基线检测到的KRAS G12D 突变，在治疗第 2 周期， 清除率达到100% ； 肿瘤标志物CA 19-9及CEA 和 急剧下降 ；并最终在 治疗3个周期后，达到部分缓解（PR） （详见下图）。 ▼该患者在RMC-9805治疗前后影像学对比 ▲图源“OneLive”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 三、小编寄语 综上，RMC-9805的初步数据显示，该药对接受过治疗的KRAS G12D 突变型胰腺导管腺癌安全且有效，为胰腺癌患者带来了新的曙光！ 做了基因检测的患者，可立即拿出检测报告查看是否存在KRAS或KRAS G12D突变，看不懂基因检测报告的病友，也可将治疗经历、近期病理及基因检测报告，提交至 全球肿瘤医生网医学部 ，进行初步评估或详细解读报告。 四、参考资料 [1]Jiang L,et al.RMC-9805, a first-in-class, mutant-selective, covalent and oral KRASG12D (ON) inhibitor that induces apoptosis and drives tumor regression in preclinical models of KRASG12D cancers[J]. Cancer research, 2023, 83(7_Supplement): 526-526. https://aacrjournals.org/cancerres/article/83/7_Supplement/526/721097/Abstract-526-RMC-9805-a-first-in-class-mutant [2]https://www.onclive.com/view/rmc-9805-triggers-tumor-regressions-in-kras-g12d-mutant-pancreatic-cancer 本文为全球肿瘤医生网原创，未经授权严禁转载

First clinical results for RMC-9805, a RAS(ON) G12D-selective inhibitor, demonstrate encouraging tolerability and antitumor activity in patients with PDAC Investor webcast to be held Friday, October 25 at 12:00 p.m. Eastern Time (ET) Oct. 25, 2024 -- Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage oncology company developing targeted therapies for RAS-addicted cancers, today announced preliminary safety and antitumor data for RMC-9805, its RAS(ON) G12D-selective inhibitor, in patients with previously treated pancreatic ductal adenocarcinoma (PDAC). These initial results were presented during the late-breaking oral session at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona on October 25, 2024. “We are pleased to report the first clinical data for RMC-9805, our novel, oral RAS(ON) G12D-selective covalent inhibitor, which demonstrate encouraging initial safety, tolerability and antitumor activity evidenced by tumor regressions,” said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. “While preliminary, these data bolster our belief that RMC-9805 has the potential to play a role in an emerging treatment paradigm for patients living with pancreatic cancer, both as monotherapy and in combinations. With today’s presentation, RMC-9805 becomes the third tri-complex compound from the Revolution Medicines pipeline to demonstrate clinical proof-of-concept, and it reaffirms our commitment to bringing novel RAS(ON) inhibitors to patients with RAS-addicted cancers.” The RMC-9805-001 Phase 1/1b study is a multicenter, open-label, dose-escalation and dose-expansion study designed to evaluate RMC-9805 in patients with advanced solid tumors harboring a KRAS G12D mutation. As of the September 2, 2024 data cutoff date, 179 patients were treated with escalating doses of RMC-9805 (ranging from 150-1200 mg once daily (QD) and 300-600 mg twice daily (BID)). Study patients had received a median of two prior therapies (range 0-9) and all had previously been treated with standard of care. As of the data cutoff date, RMC-9805 demonstrated an encouraging safety profile and was generally well tolerated across dose levels. For patients receiving 1200 mg of RMC-9805 daily (n = 99), the most common treatment-related adverse events (TRAEs) occurring in greater than 10% of patients were GI-related toxicities (nausea, diarrhea and vomiting) and rash that were primarily Grade 1 in severity and typically of limited duration. One Grade 3 TRAE of ALT elevation was reported, and no Grade 4 or 5 TRAEs were observed. Four patients (4%) experienced TRAEs that led to dose reduction and no patients discontinued treatment as a result of TRAEs. No dose limiting toxicities were observed and the maximum tolerated dose was not reached. Preliminary efficacy was assessed in PDAC patients. At a candidate recommended Phase 2 dose of 1200 mg daily (20 patients at 1200 mg QD and 20 patients at 600 mg BID), patients who received a first dose of RMC-9805 at least 14 weeks prior to the data cutoff date achieved a 30% (n = 12) objective response rate (confirmed or pending), with a disease control rate of 80% (n = 32). “Pancreatic cancer is the most RAS-addicted of all major cancers and the G12D variant is the most common RAS mutation in pancreatic cancer. No approved targeted therapies are available for these patients, making this an area of significant unmet need,” said David Hong, M.D. of MD Anderson Cancer Center, principal investigator and lead author for the RMC-9805-001 presentation. “This is a challenging disease, but we observed a promising level of antitumor activity at generally tolerable doses in this Phase 1 study." Revolution Medicines will host an investor webcast on Friday, October 25, 2024 at 12:00 p.m. Eastern Time / 6:00 p.m. Central European Standard Time to discuss the RMC-6236 and RMC-9805 monotherapy data in PDAC presented at the EORTC-NCI-AACR (“Triple”) meeting. To participate in the live webcast, participants may register in advance here. A live webcast of the call will be available on the Investors section of Revolution Medicines’ website at https://ir.revmed.com/events-and-presentations. Following the live webcast, a replay will be available on the company’s website for at least 14 days. Pancreatic cancer is one of the most lethal malignancies, characterized by its typically late-stage diagnosis, resistance to standard chemotherapy, and high mortality rate. In the U.S., recent estimates indicate that in 2024, approximately 60,000 people will be diagnosed with pancreatic cancer, and about 50,000 people will die from this aggressive disease. The most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC) and its variants, accounts for approximately 92% of all pancreatic cancer cases. Due to the lack of early symptoms and detection methods, approximately 80% of patients are diagnosed with PDAC at an advanced or metastatic stage. It is the most RAS-addicted of all major cancers, and more than 90% of patients have tumors that harbor RAS mutations. Metastatic PDAC remains one of the most common causes of cancer-related deaths in the U.S., with a five-year survival rate of approximately 3%. Revolution Medicines is a clinical-stage oncology company developing novel targeted therapies for RAS-addicted cancers. The company’s R&D pipeline comprises RAS(ON) inhibitors designed to suppress diverse oncogenic variants of RAS proteins. The company’s RAS(ON) inhibitors RMC-6236, a RAS(ON) multi-selective inhibitor, RMC-6291, a RAS(ON) G12C-selective inhibitor, and RMC-9805, a RAS(ON) G12D-selective inhibitor, are currently in clinical development. Additional development opportunities in the company’s pipeline focus on RAS(ON) mutant-selective inhibitors, including RMC-5127 (G12V), RMC-0708 (Q61H) and RMC-8839 (G13C), in addition to RAS companion inhibitors RMC-4630 and RMC-5552. The content above comes from the network. if any infringement, please contact us to modify.