Axitinib

引 言特瑞普利单抗作为首个国产PD-1抑制剂，自2018年首次获批以来，凭借其卓越的疗效与安全性，已成为国内黑色素瘤免疫治疗的中坚力量。最近，特瑞普利单抗一线治疗适应症再次获得获批，有望进一步重塑国内晚期黑色素瘤的治疗格局，开启黑色素瘤诊疗新篇章。基于此，医脉通特邀福建省肿瘤医院陈誉教授分享免疫治疗对黑色素瘤治疗格局的影响，解析特瑞普利单抗一线适应症获批的价值，并展望未来黑色素瘤治疗的发展趋势。专家简介陈誉 教授肿瘤学博士、主任医师、博士研究生导师、博士后导师福建省肿瘤医院党委委员、副院长福建医科大学肿瘤临床医学院副院长、内科学教研室主任福建省五四青年奖章获得者中华医学会肿瘤学分会肿瘤内科专家委员会委员中国临床肿瘤学会理事中国临床肿瘤学会黑色素瘤专家委员会副主任委员中国临床肿瘤学会免疫治疗专家委员会常务委员中国抗癌协会第一/二届青年理事会常务理事中国抗癌协会多原发和不明原发性肿瘤专业委员会常务委员福建省抗癌协会第一届青年理事会常务副会长福建省抗癌协会第一届黑色素瘤专业委员会主任委员福建省抗癌协会第二届肿瘤内科专业委员会副主任委员医脉通：自2018年12月特瑞普利单抗获批用于黑色素瘤二线及后线治疗，至今已有7年时间。作为福建省肿瘤医院的副院长，同时也是黑色素瘤领域著名的中青年专家，请您以贵中心为例，分享一下免疫治疗对黑色素瘤治疗格局的影响？陈誉教授在黑色素瘤领域，免疫治疗备受关注，这主要源于其在黑色素瘤治疗中的开创性探索与应用。2011年，首个免疫检查点抑制剂CTLA-4抑制剂被获批用于黑色素瘤的治疗，随后在2014年，PD-1抑制剂帕博利珠单抗和纳武利尤单抗也相继在美国获批治疗黑色素瘤。对于中国而言，真正的免疫治疗突破是在2018年，尤其是国产PD-1抑制剂特瑞普利单抗的问世，使得黑色素瘤患者终于有了可供选择的免疫治疗药物。免疫治疗药物在国内的获批极大地改善了中国黑色素瘤患者的治疗现状，从“无药可用”到“有药可选”，这是一个质的飞跃。众所周知，中国黑色素瘤的特征与欧美地区存在很大差异。欧美地区以皮肤型黑色素瘤为主，而中国则以肢端型和黏膜型为主。虽然不同亚型黑色素瘤对免疫治疗的响应率存在一定差异，但这并不妨碍免疫治疗成为黑色素瘤的基础性治疗手段。免疫治疗为患者提供了切实可用的治疗方案，这对于改善患者预后至关重要。随着免疫治疗的不断发展与深入研究，特别是多种免疫检查点抑制剂的联合应用，以及免疫检查点抑制剂与其他治疗手段（如细胞疗法）的结合使用，有望进一步提升黑色素瘤的治疗效果。相信随着更多免疫治疗策略的落地实施，将极大地改善黑色素瘤患者的生存预后，为患者带来更多的希望和可能。医脉通：请您谈谈，此次特瑞普利单抗黑色素瘤一线适应症的获批，将为我国黑色素瘤患者带来哪些价值？陈誉教授2018年，特瑞普利单抗的获批打破了我国黑色素瘤治疗的困境，为晚期黑色素瘤患者提供了全新的二线及后线治疗选择，显著提高了免疫治疗的可及性。最近，特瑞普利单抗获批用于不可切除或转移性黑色素瘤的一线治疗，进一步扩大了其针对黑色素瘤患者的治疗范围，为国内晚期黑色素瘤患者的一线免疫治疗带来了新的选择。此次特瑞普利单抗获批一线治疗适应症，主要基于其核心III期临床研究MELATORCH1。该研究是全球首个真正实现PD-1抑制剂与化疗药物达卡巴嗪头对头对照并取得阳性结果的研究，具有里程碑式的意义，对于中国黑色素瘤患者尤其重要。因为在中国黑色素瘤治疗中，化疗一直占据重要地位。而这项高质量的临床研究1证实，特瑞普利单抗一线治疗黑色素瘤相比化疗更具优势。基于该研究的卓越成果，特瑞普利单抗获得了国家药品监督管理局药品审评中心（CDE）的批准，这为其后续进入医保谈判提供了重要依据。一旦纳入医保，有望解决患者一线治疗医保支付的问题，从而大大减轻患者的经济负担，惠及更多黑色素瘤患者。此外，随着特瑞普利单抗一线治疗适应症的获批，黑色素瘤的临床研究也因此有了标杆性的对照标准。在此基础上，未来可以开展更多的免疫联合治疗研究以及其他治疗策略的探索，为黑色素瘤治疗提供更具针对性和有效性的方案。总之，特瑞普利单抗此次获批不仅是中国黑色素瘤治疗领域的重要突破，也为广大患者带来了切实的治疗价值和新的希望。医脉通：对于黑色素瘤的临床治疗，您认为还存在哪些难点及未满足的需求？从免疫治疗的角度来看，您认为当前有哪些进展值得期待？陈誉教授黑色素瘤作为一种恶性肿瘤，始终存在诸多未满足的临床需求。在我国，肢端型黑色素瘤约占总患病人群的50%，黏膜型约占25%。这两种亚型的治疗需求与欧美国家存在显著差异，因此，我们需要探索具有中国特色的治疗模式。目前，我国在黑色素瘤治疗方面已取得一定进展：针对肢端型黑色素瘤，探索了三药联合方案2；对于黏膜型黑色素瘤，则尝试了抗血管联合免疫检查点抑制剂的治疗策略，如阿昔替尼联合特瑞普利单抗3-5。随着相关研究的不断推进，我们期望通过大规模III期注册研究来改变临床实践，使更多创新药物或方案能够应用于临床。在此，我们诚挚地呼吁更多的创新药企关注黑色素瘤这一疾病，关注其独特的临床需求，推动更多创新药物的研发与应用。同时，我们也期待诸如细胞治疗、溶瘤病毒等在国外黑色素瘤治疗中已取得良好应用效果的策略，能够在国内得到更广泛的关注和推广。展望未来，在郭军教授的带领下，我国黑色素瘤专委会将在临床研究和实践方面持续发力，推动更多新药研发与突破，探索具有中国特色的黑色素瘤治疗模式，以更好地满足患者的临床需求，最终造福广大黑色素瘤患者。小 结特瑞普利单抗新适应症的获批不仅标志着中国黑色素瘤治疗进入了一个新的阶段，更体现了国产创新药物在肿瘤治疗领域的巨大潜力。在高质量临床研究的支持下，特瑞普利单抗从二线及后线治疗拓展至一线治疗，实现了对晚期黑色素瘤患者的全面覆盖，为更多患者提供了有效的治疗选择。我们期待其一线治疗适应症顺利通过医保谈判，进一步减轻患者的经济负担，让更多的患者能够用得起、用得上这一创新药物。我们相信，未来在众多专家的不懈努力与积极探索下，黑色素瘤的治疗将迎来更多创新治疗策略的突破，为患者带来更多希望。「参考文献」1. 盛锡楠, 黄钢, 方美玉等. 特瑞普利单抗对比达卡巴嗪一线治疗晚期黑色素瘤：一项多中心、随机、对照、开放标签的III期临床研究（MELATORCH研究）. 2024 CSCO.2. Mao L, Lian B, Li C, et al. Camrelizumab Plus Apatinib and Temozolomide as First-Line Treatment in Patients With Advanced Acral Melanoma: The CAP 03 Phase 2 Nonrandomized Clinical Trial. JAMA Oncol. 2023 Aug 1;9(8):1099-1107.3. Sheng XN, Yan XQ, Chi ZH, et al. Axitinib in Combination With Toripalimab, a Humanized Immunoglobulin G4 Monoclonal Antibody Against Programmed Cell Death-1, in Patients With Metastatic Mucosal Melanoma: An Open-Label Phase IB Trial[J]. J Clin Oncol. 2019 Nov 10;37(32):2987-2999. 4. Li SM, Wu XW, Yan XQ, et al. Toripalimab plus axitinib in patients with metastatic mucosal melanoma: 3-year survival update and biomarker analysis[J]. J Immunother Cancer. 2022 Feb;10(2):e004036. 5. Lian B, Li Z, Wu N, et al. Phase II clinical trial of neoadjuvant anti-PD-1 (toripalimab) combined with axitinib in resectable mucosal melanoma. Ann Oncol. 2024 Feb;35(2):211-220.撰写：Max审校：Max排版：Pan执行：Atai-THE END-本平台旨在为医疗卫生专业人士传递更多医学信息。本平台发布的内容，不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议。如该等信息被用于了解医学信息以外的目的，本平台不承担相关责任。本平台对发布的内容，并不代表同意其描述和观点。若涉及版权问题，烦请权利人与我们联系，我们将尽快处理。

Enrollment for SOL-R, the largest retinal TKI trial to date, supports randomization of at least 555 subjects SOL-1, Ocular’s first registrational trial in wet AMD, completed randomization in December 2024 and retention remains exceptional as the trial continues on track for top-line readout in 1Q 2026 These two complementary trials are intended to form the basis of an NDA submission of AXPAXLI in wet AMD BEDFORD, Mass., May 28, 2025 (GLOBE NEWSWIRE) -- Ocular Therapeutix, Inc. (NASDAQ: OCUL, “Ocular”), a fully-integrated biopharmaceutical company committed to redefining the retina experience, today announced that enrollment in the SOL-R registrational trial of its product candidate AXPAXLI™ in wet age-related macular degeneration (wet AMD) will close this week. “Completing enrollment in SOL-R – the largest retinal TKI trial to date – one year after the study was conceptualized reflects an extraordinary pace of execution and underscores our commitment to advancing innovation for patients with wet AMD,” said Pravin U. Dugel, MD, Executive Chairman, President and Chief Executive Officer. “Together with SOL-1, these two complementary, FDA-aligned registrational trials have the potential to form a robust clinical foundation to support an AXPAXLI label with a distinct superiority claim and unprecedented 6- to 12-month dosing. With recruitment ending, we are focused on disciplined trial execution, and we are encouraged by the remarkable retention and adherence to protocol we’ve observed to date in both SOL-1 and SOL-R. We’re immensely grateful to the patients, investigators, and study sites whose partnership brings us one step closer to introducing a potential new standard of care in retinal disease.” Based on current and projected screening, loading, and randomization failure rates observed in SOL-R to date, Ocular believes it has enrolled enough subjects to ensure the Company’s target randomization of at least 555 subjects in SOL-R. Subjects for SOL-R are enrolled across approximately 100 sites in the U.S., Argentina, India, and Australia. SOL-R is Ocular’s second registrational study for AXPAXLI in wet AMD. The trial is evaluating the safety and efficacy of AXPAXLI dosed every 6 months versus aflibercept (2 mg) every 8 weeks. Subjects who have been screened and enrolled will now be treated with standard of care anti-VEGF treatment and evaluated during a loading phase with the goal of randomizing at least 555 subjects. The primary endpoint of SOL-R is to demonstrate non-inferiority in mean change in best corrected visual acuity (BCVA) from baseline between the AXPAXLI and on-label aflibercept (2 mg) arms at Week 56. The trial is 90% powered to detect a non-inferiority margin of -4.5 letters of mean BCVA when compared to aflibercept (2 mg) dosed every 8 weeks. “Wet AMD continues to be a leading cause of blindness in the U.S., underscoring the need for more durable and sustainable treatments that offer improved long-term outcomes,” said Arshad M. Khanani, MD, MA, FASRS, Director of Clinical Research at Sierra Eye Associates in Reno, Nevada. “The rapid enrollment in the SOL trials highlights the retina community’s strong enthusiasm for AXPAXLI and its potential to fulfill this unmet need. The complementary SOL-1 and SOL-R trials are designed to answer key questions about AXPAXLI’s durability, flexibility, and repeatability, and build on existing monotherapy data to provide further insights into the drug’s activity. If approved, AXPAXLI could significantly reduce the treatment burden for patients with wet AMD and potentially improve long-term vision outcomes.” The FDA has agreed that together, SOL-1 and SOL-R could constitute two adequate and well-controlled trials to support a potential New Drug Application (NDA) and label for AXPAXLI in wet AMD. These complementary trials were designed in alignment with FDA guidance and validated through a Special Protocol Assessment (SPA) agreement for SOL-1, and written responses for SOL-R received in 2024. Pending positive results from SOL-1 and SOL-R, Ocular plans to submit an NDA for FDA review following 56-week data from SOL-R. “SOL-1 and SOL-R were intentionally designed as complementary trials to provide a comprehensive evaluation of AXPAXLI, while strictly adhering to FDA guidance,” said Peter K. Kaiser, MD, Chief Development Officer of Ocular Therapeutix. “Consistent with FDA recommendations for adequately masked and controlled trials, neither trial uses sham injections, and this mitigates the potential for bias from inadequate masking. Through thoughtful and innovative patient selection criteria and complementary trial designs, we aimed to de-risk each study population. Given the rigorous enrollment criteria, we’re especially pleased with the rapid pace of enrollment across both trials. We are confident that this strategic approach not only positions us strongly for potential regulatory approval but also sets the stage for AXPAXLI to become a differentiated treatment in retinal disease.” About AXPAXLI AXPAXLI™ (also known as OTX-TKI) is an investigational, bioresorbable, intravitreal hydrogel incorporating axitinib, a small molecule, multi-target, tyrosine kinase inhibitor (TKI) with anti-angiogenic properties, being evaluated for the treatment of wet AMD, diabetic retinopathy, diabetic macular edema, and other retinal diseases. About the SOL-R Study The registrational Phase 3 SOL-R trial (NCT06495918) is designed to evaluate the safety and efficacy of AXPAXLI in a multi-center, double-masked, randomized (2:2:1), three-arm study that involves approximately 100 sites located in the U.S., Argentina, India, and Australia. The trial is intended to randomize approximately 555 subjects who are treatment-naïve or were newly diagnosed with wet AMD in the study eye within about four months prior to enrollment. This non-inferiority trial reflects a patient enrichment strategy over the six months prior to randomization that includes three screening doses of any anti-VEGF therapy, excluding brolucizumab-dbll, and monitoring to exclude those subjects with significant retinal fluid fluctuations. Subjects that continue to meet eligibility criteria will enter a run-in period and receive two loading doses of aflibercept (2 mg) prior to Day 1. Subjects in the first arm receive a single dose of AXPAXLI at Day 1 and are re-dosed at Weeks 24, 48, and 72. Subjects in the second arm receive aflibercept (2 mg) on-label every eight weeks. Subjects in the third arm receive a single dose of aflibercept (8 mg) at Day 1 and are re-dosed at Weeks 24, 48, and 72, aligned with the AXPAXLI treatment arm for adequate masking. Subjects will be followed for safety until the end of Year 2. Throughout the study, subjects are assessed monthly. Trial subjects and designated study personnel will remain masked through the end of Year 2. Subjects in any arm that meet pre-specified rescue criteria will receive a supplemental dose of aflibercept (2 mg). The pre-specified rescue criteria include loss of ≥ 10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters of BCVA from baseline or a combination of worsening anatomical measures and BCVA loss. The primary endpoint of SOL-R is to demonstrate non-inferiority in mean BCVA change from baseline between the AXPAXLI and on-label aflibercept (2 mg) arms at Week 56. As per the protocol agreed to by the FDA, the non-inferiority margin for the lower bound is -4.5 letters of mean BCVA when compared to aflibercept (2 mg) dosed every eight weeks. In a written Type C response received in August 2024, and a subsequent written response received in December 2024, the FDA agreed that the SOL-R repeat dosing wet AMD study, with a primary endpoint at Week 56, should be appropriate as an adequate and well-controlled study in support of a potential New Drug Application and product label for wet AMD. About the SOL-1 Study The registrational Phase 3 SOL-1 trial (NCT06223958) is designed to evaluate the safety and efficacy of AXPAXLI in a multi-center, double-masked, randomized (1:1), parallel group study that involves more than 100 clinical trial sites located in the U.S. and Argentina. In December 2024, the trial completed randomization of 344 evaluable treatment-naïve subjects with a diagnosis of wet AMD in the study eye. The superiority study has an eight-week loading segment prior to randomization. During the loading segment, subjects who have 20/80 vision or better and who satisfy other enrollment criteria receive two doses of aflibercept (2 mg) at Week -8 and Week -4. Eligible subjects who achieve best corrected visual acuity (BCVA) of 20/20 at Day 1 or gain at least 10 ETDRS letters at Day 1 are then randomized to receive a single dose of AXPAXLI or a single dose of aflibercept (2 mg). At Week 52 and at Week 76, all subjects are re-dosed with their respective initial treatment of AXPAXLI or aflibercept (2 mg). Subjects will be followed for safety until the end of Year 2. Throughout the study, subjects are assessed monthly. Trial subjects and designated study personnel will remain masked through the end of Year 2. The clinical trial protocol requires that, during the study, subjects in either arm meeting pre-specified rescue criteria will receive a supplemental dose of aflibercept (2 mg). The primary endpoint of SOL-1 is the proportion of subjects who maintain visual acuity, defined as a loss of <15 ETDRS letters of BCVA, at Week 36. Subjects will continue to be evaluated for durability up to Week 52. The study is being conducted under a Special Protocol Assessment (SPA) agreement with the FDA. About Wet AMD Wet age-related macular degeneration (wet AMD) is a leading cause of severe, irreversible vision loss affecting approximately 14.5 million individuals globally and 1.7 million in the United States alone (2024 Market Scope® Retinal Pharmaceuticals Market Report). Wet AMD causes vision loss due to abnormal new blood vessel growth and hyperpermeability and associated retinal vascularity in the macula, which is primarily stimulated by local upregulation of vascular endothelial growth factor (VEGF). Without prompt and continuous treatment to control this exudative activity, patients develop irreversible vision loss. With proper treatment, patients may maintain visual function for a period of time and may temporarily regain lost vision. Challenges with current therapies include pulsatile, repeated intraocular injections, treatment-related adverse events and up to 40% patient discontinuation within one year of initiating treatment with continued disease progression. Taken together, these factors lead to undertreatment and a lack of long-term vision improvement for patients. About Ocular Therapeutix, Inc. Ocular Therapeutix, Inc. is a fully-integrated biopharmaceutical company committed to redefining the retina experience. AXPAXLI™ (also known as OTX-TKI), Ocular’s investigational product candidate for retinal disease, is an axitinib intravitreal hydrogel based on its ELUTYX™ proprietary bioresorbable hydrogel-based formulation technology. AXPAXLI is currently in Phase 3 clinical trials for wet age-related macular degeneration (wet AMD). Ocular’s pipeline also leverages the ELUTYX technology in its commercial product DEXTENZA®, an FDA-approved corticosteroid for the treatment of ocular inflammation and pain following ophthalmic surgery in adults and pediatric patients and ocular itching associated with allergic conjunctivitis in adults and pediatric patients aged two years or older, and in its investigational product candidate PAXTRAVA™ (also known as OTX-TIC), which is a travoprost intracameral hydrogel that is currently in a Phase 2 clinical trial for the treatment of open-angle glaucoma or ocular hypertension. Follow the Company on its website, LinkedIn, or X. The Ocular Therapeutix logo and DEXTENZA® are registered trademarks of Ocular Therapeutix, Inc. AXPAXLI™, PAXTRAVA™, ELUTYX™, and Ocular Therapeutix™ are trademarks of Ocular Therapeutix, Inc. Forward-Looking Statements Any statements in this press release about future expectations, plans, and prospects for the Company; the development, regulatory status of and regulatory submissions regarding the Company’s product candidates; the design of, and the timing of the screening, enrollment and randomization of patients in and the availability of data from the Company’s SOL-1 and SOL-R Phase 3 clinical trials of AXPAXLI (also known as OTX-TKI) for the treatment of wet AMD; the Company’s plans to advance the development of AXPAXLI; the potential utility or adoption, if approved, of any of the Company’s product candidates; and other statements containing the words “anticipate”, “believe”, “estimate”, “expect”, “intend”, “designed”, “goal”, “may”, “might”, “plan”, “predict”, “project”, “target”, “potential”, “will”, “would”, “could”, “should”, “continue”, and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors. Such forward-looking statements involve substantial risks and uncertainties that could cause the Company’s development programs, future results, performance, or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the timing and costs involved in commercializing any product or product candidate that receives regulatory approval; the ability to retain regulatory approval of any product or product candidate that receives regulatory approval; the initiation, design, timing, conduct and outcomes of ongoing and planned clinical trials; the risk that fewer enrolled patients than expected will ultimately be randomized into the SOL-R clinical trial; the risk that the FDA will not agree with the Company’s interpretation of the written agreement under the Special Protocol Assessment for the SOL-1 trial; the risk that the FDA may not agree that the protocol and statistical analysis plan of SOL-R or that the data generated by the SOL-1 and SOL-R trials support marketing approval, even if the trials are successful; the risk that the Company and the FDA may not agree on the registrational pathway for any of its product candidates; uncertainty as to whether the data from earlier clinical trials will be predictive of the data of later clinical trials, particularly later clinical trials that have a different design or utilize a different formulation than the earlier trials, whether preliminary or interim data from a clinical trial (including masked safety or masked rescue data from the Company’s SOL-1 trial) will be predictive of final data from such trial, or whether data from a clinical trial assessing a product candidate for one indication will be predictive of results in other indications; availability of data from clinical trials and expectations for regulatory submissions and approvals; the Company’s scientific approach and general development progress; and other factors discussed in the “Risk Factors” section contained in the Company’s quarterly and annual reports on file with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company’s views as of the date of this press release. The Company anticipates that subsequent events and developments may cause the Company’s views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so, whether as a result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing the Company’s views as of any date subsequent to the date of this press release. Investors & Media Ocular Therapeutix, Inc. Bill Slattery Vice President, Investor Relations bslattery@ocutx.com