Darolutamide

REVTORPYK™ (gedatolisib) approved by the U.S. FDA for the treatment of HR+/HER2- PIK3CA Wild-Type locally advanced or metastatic breast cancer on July 14, 2026; on track for commercial launch late third quarter 2026 NCCN® Clinical Practice Guidelines recommended REVTORPYK in combination with fulvestrant, with or without palbociclib, as a preferred Category 1 option for second-line therapy in HR+/HER2- advanced breast cancer The Phase 3 PIK3CA mutant cohort of the VIKTORIA-1 trial achieved its primary endpoint by doubling the likelihood of survival without disease progression or death compared to alpelisib plus fulvestrant; a supplemental New Drug Application (“sNDA”) is planned for submission in the third quarter of 2026 The Phase 3 VIKTORIA-2 trial was expanded to include a second study evaluating gedatolisib as first-line treatment in patients with endocrine-sensitive HR+/HER2- advanced breast cancer Completed issuance of $575.0 million convertible note offering, with net proceeds of $557.2 million Management to host webcast and conference call today, August 13, 2026, at 4:30 p.m. EDT MINNEAPOLIS, Aug. 13, 2026 (GLOBE NEWSWIRE) -- Celcuity Inc. (Nasdaq: CELC), a biotechnology company focused on developing and commercializing targeted therapies for the treatment of multiple solid tumor indications, today announced financial results for the second quarter ended June 30, 2026 and other recent business developments. “Celcuity made monumental progress these past few months, achieving critical clinical and regulatory milestones related to gedatolisib. With the FDA approval of REVTORPYK, positive results from the PIK3CA MT cohort of the pivotal VIKTORIA-1 study, and a preferred Category 1 recommendation in the NCCN Guidelines®, we are well positioned to address a significant unmet need for the tens of thousands of patients affected each year by HR+/HER2-, locally advanced or metastatic breast cancer whose disease has progressed after endocrine therapy,” said Brian Sullivan, CEO and co-founder of Celcuity. “We are on track to begin shipping REVTORPYK late in the third quarter of 2026, and we look forward to making this important therapy available to patients with locally advanced or metastatic breast cancer.” Mr. Sullivan added, “Based on the positive data from the PIK3CA mutant cohort of the Phase 3 VIKTORIA-1 study, we plan to submit an sNDA to FDA in the third quarter of 2026. Additionally, our VIKTORIA-2 study was expanded to enable evaluation of treatment-naive patients who have endocrine-sensitive breast cancer, positioning gedatolisib regimens to potentially be available for nearly all patients in the first- and second-line setting, irrespective of their endocrine sensitivity or PIK3CA mutation status.” Clinical Highlights HR+/HER2- Advanced Breast Cancer 2 nd Line Setting – PIK3CA Wild-Type Following the unprecedented results from the PIK3CA WT cohort of the VIKTORIA-1 Phase 3 clinical trial, on July 14, 2026 Celcuity announced that the U.S. Food and Drug Administration (“FDA”) had approved REVTORPYK, the company’s pan-PI3K, mTORC1/2 inhibitor, for the treatment of patients with hormone receptor positive (“HR+”), human epidermal growth factor 2 receptor negative (”HER2-“), locally advanced or metastatic breast cancer (“ABC”) without a PIK3CA mutation detected following progression on or after treatment with at least one line of endocrine therapy in the metastatic setting. Celcuity subsequently announced that REVTORPYK in combination with fulvestrant, with or without palbociclib, was recommended by the National Comprehensive Cancer Network® (“NCCN®”) as a preferred Category 1 second-line and/or subsequent-line therapy for the treatment of patients with HR+/HER2- breast cancer without a PIK3CA mutation following progression on or after treatment with at least one line of endocrine therapy. The build-out of the commercialization infrastructure needed to support a successful launch of REVTORPYK is complete and commercial launch activities for REVTORPYK commenced immediately after approval. Shipments of REVTORPYK are expected to begin late in the third quarter of 2026. To make gedatolisib available to patients prior to commercial availability of REVTORPYK, last week Celcuity opened an Expanded Access Program (EAP) to participating physicians on behalf of eligible patients, and we have begun to distribute gedatolisib to those physicians. 2 nd Line Setting – PIK3CA Mutant-Type Gedatolisib continued to demonstrate a differentiated clinical pro different patient populations when combined with fulvestrant, with or without palbociclib. At the 2026 American Society of Clinical Oncology (“ASCO”) Annual Meeting, detailed results from the PIK3CA MT cohort of the global VIKTORIA-1 Phase 3 study were presented at a late-breaking abstract Oral Session. The study demonstrated statistically significant and clinically meaningful improvements in the primary endpoint of progression-free survival (“PFS”) compared with alpelisib plus fulvestrant, with a manageable safety profile. Gedatolisib plus fulvestrant and palbociclib (the “gedatolisib-triplet”) reduced the risk of disease progression or death by 50% vs. alpelisib plus fulvestrant (HR=0.50; 95% CI: 0.37–0.68; p<0.0001). Median PFS was 11.1 months with the gedatolisib triplet versus 5.6 months with alpelisib plus fulvestrant. Gedatolisib plus fulvestrant (the “gedatolisib-doublet”) reduced the risk of disease progression or death by 49% vs. alpelisib plus fulvestrant (HR=0.51; 95% CI: 0.33–0.79; descriptive p=0.0013). Median PFS was 11.3 months with the gedatolisib-doublet versus 5.6 months with alpelisib plus fulvestrant. Gedatolisib regimens demonstrated robust and durable responses: 49% objective response rate (“ORR”) and median duration of response (“DoR”) of 15.7 months for the gedatolisib-triplet and 36% ORR and median DoR of 24.2 months for the gedatolisib-doublet. The safety data for the gedatolisib-triplet and -doublet were consistent with previously reported data from the PIK3CA wild-type cohort of VIKTORIA-1. Analyses of the treatment discontinuation rate due to an adverse event for gedatolisib and alpelisib in the PIK3CA MT cohort were updated using the same methodology that determined the discontinuation rate due to an adverse event for the PIK3CA WT cohort presented in the REVTORPYK label. For patients who received the gedatolisib triplet and gedatolisib doublet, 5.2% and 3.8% of patients discontinued gedatolisib due to an adverse event, respectively. For patients who received alpelisib, 19.1% discontinued treatment with alpelisib due to an adverse event. Celcuity intends to submit these data to the FDA in the third quarter as an sNDA and to submit VIKTORIA-1 data to other regulatory authorities outside the U.S. following the sNDA submission. Analyses of the mean number of gedatolisib treatment cycles patients received in the PIK3CA WT and MT cohorts of the VIKTORIA-1 Phase 3 trial were also updated as of August 2, 2026, with a median follow-up period of approximately 21 months and 17 months for the PIK3CA WT and MT cohorts, respectively. For patients who received the gedatolisib-triplet, the mean number of treatment cycles on gedatolisib was 9.0 and 10.0 cycles in the PIK3CA WT and MT cohorts, respectively, with 12% (16) and 22% (34) of patients still receiving gedatolisib therapy in each cohort, respectively. For patients who received the gedatolisib-doublet, the mean number of treatment cycles on gedatolisib was 9.7 and 11.3 cycles in the PIK3CA WT and MT cohorts, respectively, with 12% (15) and 19% (10) of patients still receiving gedatolisib therapy in each cohort, respectively. Celcuity expects to provide further updates to results from both the PIK3CA MT and WT cohorts of VIKTORIA-1 at medical conferences in the fourth quarter. 1 s t Line Setting Celcuity continues to advance gedatolisib combined with palbociclib and endocrine therapy in the first-line setting for patients with HR+/HER2- ABC through its ongoing Phase 3 VIKTORIA-2 clinical trial. The VIKTORIA-2 trial was expanded in the second quarter 2026 to include a second study (Study 2) evaluating the efficacy and safety of gedatolisib in combination with palbociclib and letrozole in patients with treatment-naive endocrine-sensitive HR+/HER2- ABC. Study 1 of the VIKTORIA-2 trial is evaluating gedatolisib in combination with palbociclib and fulvestrant in patients with treatment-naive endocrine-resistant HR+/HER2- ABC. Metastatic Castration-Resistant Prostate Cancer (“mCRPC”) Development of gedatolisib in combination with darolutamide continues to advance. In the dose finding portion of Celcuity’s Phase 1b study, evaluation of a 240 mg dose of gedatolisib was completed. No adverse events led to treatment discontinuation of gedatolisib and dose limiting toxicity criteria for dose reduction were not met. Evaluation of a 300 mg dose is ongoing. Once the Phase 1/1b portion of the study is completed, Celcuity expects to select the recommended phase 2 dose level(s) and control arm options for the randomized Phase 2 portion of the study. The company expects to provide updated clinical data and additional visibility into its mCRPC development strategy during the fourth quarter of 2026. Other Recent Developments In June 2026, the Company conducted a public offering of 0.250% convertible senior notes due 2032. The net proceeds from the offering were $557.2 million, after deducting underwriting discounts and commissions and the Company’s estimated offering expenses. The Company utilized $137.0 million of the net proceeds to prepay term loan debt. Celcuity’s advancement of a subcutaneous gedatolisib formulation is ongoing with the goal of demonstrating clinical equivalence to the current intravenous formulation of gedatolisib. The subcutaneous formulation is aimed to support potential future indications for gedatolisib regimens that may result in duration of treatment periods greater than several years. Second Quarter 2026 Financial Results Unless otherwise stated, all comparisons are for the second quarter ended June 30, 2026, compared to the second quarter ended June 30, 2025. Net loss for the second quarter of 2026 was $78.9 million, or $1.44 per share, compared to a net loss of $45.3 million, or $1.04 per share, for the prior year period. Non-GAAP adjusted net loss for the second quarter of 2026 was $58.7 million, or $1.07 per share, compared to non-GAAP adjusted net loss of $40.5 million, or $0.93 per share, for the prior year period. Non-GAAP adjusted net loss excludes stock-based compensation expense, non-cash interest expense, non-cash investment (income) expense and loss on debt extinguishment. Because these items have no impact on Celcuity’s cash position, management believes non-GAAP adjusted net loss better enables Celcuity to focus on cash used in operations. For a reconciliation of financial measures calculated in accordance with generally accepted accounting principles in the United States (“GAAP”) to non-GAAP financial measures, please see the financial tables at the end of this press release. Total operating expenses were $66.1 million for the second quarter of 2026, compared to $44.0 million for the prior year period. Research and development (“R&D”) expenses were $31.1 million for the second quarter of 2026, compared to $36.4 million for the prior year period. The $5.3 million decrease in R&D expenses was primarily due to a $7.0 million decrease in clinical trial costs, which was primarily driven by decreased costs for the VIKTORIA-1 Phase 3 clinical trial, and a $5.0 million decrease in license milestone costs. These decreases were partially offset by a $3.8 million increase in employee-related and consulting expenses, of which $0.9 million related to stock-based compensation, and a $2.9 million increase in manufacturing and other costs. Selling, general and administrative (“SG&A”) expenses were $35.0 million for the second quarter of 2026, compared to $7.6 million for the prior year period. The $27.4 million increase in SG&A expenses was primarily due to a $14.5 million increase in employee-related expenses, of which $3.3 million related to stock-based compensation. The increase in employee-related expenses was primarily driven by the hiring of additional personnel within our commercial function to support the anticipated launch of REVTORPYK. The remaining $12.9 million increase was primarily due to a $10.8 million increase in costs to support pre-commercial launch activities, including consulting expenses, professional fees and expanding infrastructure costs, and a $2.1 million increase in other administrative expenses. In the aggregate, $23.4 million of the $27.4 million SG&A increase related to commercial headcount additions and other launch-related activities. Net cash used in operating activities for the second quarter of 2026 was $55.4 million, compared to $36.2 million for the prior year period. Cash, cash equivalents and short-term investments were $754.0 million at the end of the second quarter of 2026. We expect that our current cash, cash equivalents and short-term investments will finance our operations at least into 2029. Webcast and Conference Call Information To participate in the teleconference, domestic callers should dial 1-800-717-1738 and international callers should dial 1-646-307-1865. A live webcast presentation can also be accessed using this weblink: . A replay of the webcast will be available on the Celcuity website following the live event. About REVTORPYK (gedatolisib) REVTORPYK (gedatolisib) is a kinase inhibitor indicated in combination with fulvestrant, with or without palbociclib, for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer without a PIK3CA mutation detected following progression on or after treatment with at least one line of endocrine therapy in the metastatic setting. Please click here for Important Safety Information and Full Prescribing Information for REVTORPYK. About Celcuity We are a biotechnology company focused on developing and commercializing targeted therapies for the treatment of multiple solid tumor indications. Our first FDA-approved product is REVTORPYK TM (gedatolisib), a potent, pan-PI3K and mTORC1/2 inhibitor that comprehensively blockades the PAM pathway. Its mechanism of action and pharmacokinetic properties are differentiated from other currently approved and investigational therapies that target PI3Kα, AKT or mTORC1 alone or together. Our Phase 3 clinical trial, VIKTORIA-1, evaluated gedatolisib in combination with fulvestrant, with or without palbociclib, for the treatment of patients with HR+/HER2- ABC. Data from this trial is the basis for FDA approval of REVTORPYK for use in adult patients with HR+/HER2- ABC without a PIK3CA mutation detected following progression on or after treatment with at least one line of endocrine therapy in the metastatic setting. Results for the PIK3CA mutant cohort of the VIKTORIA-1 study have been released. Our Phase 3 clinical trial, VIKTORIA-2, is an ongoing trial incorporating two independent studies, Study 1 and Study 2, in two separate cohorts of patients with ABC who are treatment-naive in the advanced setting. Study 1 is evaluating gedatolisib in combination with palbociclib and fulvestrant as first-line treatment for patients with endocrine-resistant HR+/HER2- ABC. Study 2 is evaluating gedatolisib in combination with palbociclib and letrozole as first-line treatment for patients with endocrine-sensitive HR+/HER2- ABC. A Phase 1b/2 clinical trial, CELC-G-201, evaluating gedatolisib in combination with darolutamide in patients with metastatic castration-resistant prostate cancer, is ongoing. More detailed information about Celcuity’s active clinical trials can be found at ClinicalTrials.gov . Celcuity is headquartered in Minneapolis. Further information about Celcuity and its products, including important safety information and full prescribing information can be found at . Follow us on LinkedIn and X . Forward Looking Statements This press release contains statements that constitute “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 including statements relating to REVTORPYK and the potential therapeutic benefits of gedatolisib; the size, design and timing of the Company’s clinical trials; the Company’s interpretation of clinical trial data; the status and timing of the submission, and the FDA’s review, of the Company’s sNDA for gedatolisib, and for making comparable filings with other regulatory authorities outside the U.S.; the market opportunity for gedatolisib; the Company’s expectations regarding the timing of and its ability to commercialize REVTORPYK; the Company’s strategy, marketing and commercialization plans, including the benefits of strategic decisions regarding studies and trials; other expectations with respect to gedatolisib, including subcutaneous formulations to support potential future indications for gedatolisib regimens; the Company’s anticipated use of cash; and the strength of its balance sheet. Words such as, but not limited to, “look forward to,” “believe,” “expect,” “anticipate,” “estimate,” “intend,” “confidence,” “encouraged,” “potential,” “plan,” “targets,” “likely,” “may,” “will,” “would,” “should” and “could,” and similar expressions or words identify forward-looking statements. The forward-looking statements included in this press release are based on management’s current expectations and beliefs which are subject to a number of risks, uncertainties and factors, including that the Company’s topline clinical results are based on an ongoing analysis of efficacy and safety data and such data may change following a more comprehensive review of the data related to the clinical trial; unforeseen delays in the Company’s clinical trials or the submission, and FDA’s review of, its sNDA for gedatolisib; the Company’s ability to obtain regulatory approval of its sNDA and maintain regulatory approvals to commercialize REVTORPYK in the U.S. and obtain regulatory approval of gedatolisib outside the U.S., and the market acceptance of REVTORPYK; the development of therapies and tools competitive with gedatolisib; and the Company’s ability to access capital upon favorable terms. In addition, all forward-looking statements are subject to other risks detailed in the Company’s Annual Report on Form 10-K for the year ended December 31, 2025, as such risks may be updated in its subsequent filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by these cautionary statements, and the Company undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof. References: 1. Internal estimates using data from National Cancer Institute, SEER, 2024; Pan, H, NEJM, 2017;377:1836-46; Dowsett, M 2009; Salvo, E. M. et al. 2021 © 2026 Celcuity Inc. All rights reserved. REVTORPYK and the Celcuity logo are trademarks of Celcuity Inc. Contacts: Celcuity Inc. Brian Sullivan, bsullivan@celcuity.com Vicky Hahne, vhahne@celcuity.com (763) 392-0123 Jodi Sievers, jsievers@celcuity.com (415) 494-9924 Celcuity Inc. Condensed Balance Sheets (in thousands) June 30, 2026 December 31, 2025 (unaudited) Assets Current assets: Cash and cash equivalents $ 182,049 $ 165,703 Investments 571,995 275,794 Prepaid clinical trial costs 12,996 18,896 Other current assets 8,801 5,266 Total current assets 775,841 465,659 Property and equipment, net 611 499 Intangible assets, net 50,000 — Operating lease right-of-use assets 1,107 51 Other non-current assets 661 349 Total assets $ 828,220 $ 466,558 Liabilities and stockholders' equity (deficit) Current liabilities: Accounts payable $ 8,093 $ 6,407 Accrued clinical trial costs 7,942 16,826 Accrued license milestone 50,000 5,000 Other accrued expenses 20,581 15,865 Operating lease liabilities, current 257 54 Total current liabilities 86,873 44,152 Operating lease liabilities, non-current 893 — Convertible notes 753,235 195,324 Note payable — 126,527 Total liabilities 841,001 366,003 Total stockholders' equity (deficit) (12,781 ) 100,555 Total liabilities and stockholders' equity (deficit) $ 828,220 $ 466,558 Celcuity Inc. Condensed Statements of Operations (unaudited) (in thousands, except share and per share amounts) Three Months Ended June 30, Six Months Ended June 30, 2026 2025 2026 2025 Operating expenses: Research and development (1) $ 31,077 $ 36,415 $ 64,140 $ 66,174 Selling, general and administrative (1) 35,041 7,594 52,485 13,968 Total operating expenses 66,118 44,009 116,625 80,142 Loss from operations (66,118 ) (44,009 ) (116,625 ) (80,142 ) Other (expense) income: Interest expense (5,423 ) (3,204 ) (11,508 ) (6,387 ) Interest income 4,154 1,945 7,905 4,264 Loss on debt extinguishment (11,477 ) — (11,477 ) — Other expense, net (12,746 ) (1,259 ) (15,080 ) (2,123 ) Net loss before income taxes (78,864 ) (45,268 ) (131,705 ) (82,265 ) Income taxes — — — — Net loss $ (78,864 ) $ (45,268 ) $ (131,705 ) $ (82,265 ) Net loss per share, basic and diluted $ (1.44 ) $ (1.04 ) $ (2.41 ) $ (1.90 ) Weighted average common shares outstanding, basic and diluted 54,816,437 43,663,364 54,640,608 43,359,748 (1 ) Certain prior period amounts have been reclassified from research and development expenses to selling, general and administrative expenses to conform to the current period presentation. Cautionary Statement Regarding Non-GAAP Financial Measures This press release contains references to non-GAAP adjusted net loss and non-GAAP adjusted net loss per share. Management believes these non-GAAP financial measures are useful supplemental measures for planning, monitoring, and evaluating operational performance as they exclude stock-based compensation expense, non-cash interest expense, non-cash investment (income) expense and loss on debt extinguishment from net loss and net loss per share. Management excludes these items because they do not impact Celcuity’s cash position, which management believes better enables Celcuity to focus on cash used in operations. However, non-GAAP adjusted net loss and non-GAAP adjusted net loss per share are not recognized measures under GAAP and do not have a standardized meaning prescribed by GAAP. As a result, management’s method of calculating non-GAAP adjusted net loss and non-GAAP adjusted net loss per share may differ materially from the method used by other companies. Therefore, non-GAAP adjusted net loss and non-GAAP adjusted net loss per share may not be comparable to similarly titled measures presented by other companies. Investors are cautioned that non-GAAP adjusted net loss and non-GAAP adjusted net loss per share should not be construed as alternatives to net loss, net loss per share or other statements of operations data (which are determined in accordance with GAAP) as an indicator of Celcuity’s performance or as a measure of liquidity and cash flows. Celcuity Inc. Reconciliation of GAAP Net Loss to Non-GAAP Adjusted Net Loss and GAAP Net Loss Per Share to Non-GAAP Adjusted Net Loss Per Share (unaudited) (in thousands, except share and per share amounts) Three Months Ended June 30, Six Months Ended June 30, 2026 2025 2026 2025 GAAP net loss $ (78,864 ) $ (45,268 ) $ (131,705 ) $ (82,265 ) Adjustments to net loss: Stock-based compensation Research and development (1), (2) 2,240 1,261 4,352 2,425 Selling, general and administrative (1), (3) 4,664 1,443 7,877 2,723 Non-cash interest expense (4) 1,471 789 3,048 1,589 Non-cash investment (income) expense (5) 332 1,286 (551 ) 340 Loss on debt extinguishment (6) 11,477 — 11,477 — Non-GAAP adjusted net loss $ (58,680 ) $ (40,489 ) $ (105,502 ) $ (75,188 ) GAAP net loss per share - basic and diluted $ (1.44 ) $ (1.04 ) $ (2.41 ) $ (1.90 ) Adjustments to net loss: Stock-based compensation Research and development (1), (2) 0.04 0.03 0.08 0.06 Selling, general and administrative (1), (3) 0.08 0.03 0.14 0.06 Non-cash interest expense (4) 0.03 0.02 0.06 0.04 Non-cash investment (income) expense (5) 0.01 0.03 (0.01 ) 0.01 Loss on debt extinguishment (6) 0.21 — 0.21 — Non-GAAP adjusted net loss per share - basic and diluted $ (1.07 ) $ (0.93 ) $ (1.93 ) $ (1.73 ) Weighted average common shares outstanding, basic and diluted 54,816,437 43,663,364 54,640,608 43,359,748 (1 ) Certain prior period amounts have been reclassified from research and development expenses to selling, general and administrative expenses to conform to the current period presentation. (2 ) To reflect a non-cash adjustment to operating expenses for research and development stock-based compensation. (3 ) To reflect a non-cash adjustment to operating expenses for selling, general and administrative stock-based compensation. (4 ) To reflect a non-cash adjustment to other (expense) income for amortization of debt issuance costs and discount and payment-in-kind interest related to the issuance of the convertible notes and note payable. (5 ) To reflect a non-cash adjustment to other (expense) income for accretion on investments and change in accrued interest income. (6 ) To reflect a non-cash adjustment to other (expense) income for loss on extinguishment related to the repayment of the note payable.

点击蓝字 关注我们 编者按 唾液腺癌是一类小众但高度异质的头颈部恶性肿瘤，其中唾液导管癌恶性程度高、极易远处转移，晚期阶段长期缺乏标准化全身治疗手段。传统化疗毒副反应重，HER2靶向治疗仅能覆盖少数基因扩增患者，临床亟需低毒、高效、可长期维持的非化疗方案。雄激素受体（AR）在绝大多数唾液导管癌中高表达，是极具潜力的治疗靶点，但既往单用AR抑制剂或单纯LHRH激动剂临床获益有限，联合雄激素阻断（CAB）的价值一直缺少高质量前瞻性证据支撑。 近日，Journal of Clinical Oncology（JCO）发表的DISCOVARY Ⅱ期研究，是全球首个前瞻性评估新一代AR抑制剂达罗他胺单药、联合戈舍瑞林用于AR阳性晚期唾液腺癌的多中心临床试验。研究清晰证实：单纯达罗他胺抗肿瘤作用微弱，而达罗他胺联合戈舍瑞林的全通路雄激素阻断策略可实现近45%客观缓解率，中位无进展生存期较单药延长一倍，且不良反应更轻、患者生活质量稳定维持。 该研究填补了晚期AR阳性唾液腺癌内分泌治疗的高级别证据空白，为不耐受化疗、HER2阴性、老年体弱患者提供了全新的免化疗治疗选择，也为临床建立“AR常规检测+内分泌靶向优先”的诊疗思路提供了关键依据，值得头颈肿瘤、内分泌肿瘤临床医生重点关注。 一、研究背景 唾液腺癌（SGC）占全部头颈部恶性肿瘤的5%～7%，属于罕见上皮源性肿瘤，病理亚型繁杂；其中唾液导管癌（SDC）侵袭性最强，一旦进展至不可切除局部晚期（LA）或复发/转移（R/M）阶段，患者中位总生存期通常不足2年，全球尚无统一标准全身治疗方案。 当前临床困境十分突出： 1.细胞毒性化疗是晚期患者主要姑息手段，但有效率偏低、骨髓抑制、消化道反应等毒性显著，老年、基础疾病多患者耐受差； 2.HER2靶向药物仅适用于HER2过表达/扩增人群，覆盖患者比例有限； 3.免疫单药在唾液腺癌中整体应答率低，获益人群难以筛选。 AR在70%～90%唾液导管癌中呈阳性表达，是公认的核心驱动靶点。既往临床探索显示：一代抗雄药物、恩扎卢胺单药、LHRH激动剂单用均疗效欠佳；而小样本回顾性与Ⅱ期研究提示，AR抑制剂联合LHRH激动剂的联合雄激素阻断（CAB）能更全面抑制雄激素信号，抗肿瘤活性更强。 达罗他胺为第二代非甾体AR信号抑制剂，拥有AR结合亲和力，血脑屏障穿透率极低，在前列腺癌Ⅲ期研究中已证实联合雄激素剥夺治疗（ADT）疗效与安全性优异。但此前尚无前瞻性试验验证其在唾液腺癌中的价值。为此日本12家中心联合开展DISCOVARY序贯双队列Ⅱ期研究（NCT05694819），头对头探索达罗他胺单药、达罗他胺联合戈舍瑞林两种内分泌方案的临床价值。 二、研究设计与入组人群 DISCOVARY为开放标签、多中心、序贯非随机双队列Ⅱ期研究，两个队列分阶段入组，仅做描述性探索对比，未预设统计学优效性检验： 1.单药队列（2020.4~2021.2）：达罗他胺600 mg口服，每日2次；累计入组30例，6例筛选失败，最终24例接受治疗； 2.联合CAB队列（2022.10~2023.8）：达罗他胺600 mg bid+戈舍瑞林3.6 mg皮下注射，每28天1次；累计入组34例，1例筛选失败，最终33例接受治疗。 核心入排标准 1.年龄≥20周岁，病理确诊不可切除局部晚期/复发转移性唾液腺癌，存在RECISTv1.1可测量病灶，ECOG PS 0~2分，肝肾功能、造血功能达标； 2.既往未接受任何AR抑制剂、GnRH激动剂、CYP17抑制剂等内分泌抗肿瘤治疗； 3.单药队列：中心病理免疫组化确认AR阳性（细胞核染色≥1%），仅纳入唾液导管癌、非特异性腺癌、多形性腺瘤癌变； 4.联合队列：初筛可采用本地病理AR检测，不限病理亚型；所有样本后续统一中心复核AR表达，2例中心判定AR阴性患者剔除疗效分析集（mFAS=31）。 基线人群特征 全部57例治疗患者以男性为主，多数ECOG 0分，伴远处转移（肺、远处淋巴结、骨为高发转移部位），原发肿瘤最常见于腮腺；约半数患者既往接受含铂系统化疗。联合队列唾液导管癌占比更高，两组基线特征仅做描述统计，未进行组间差异检验。 三、给药方案与评估标准 1 治疗给药 28天为1个治疗周期，持续用药直至疾病进展、不可耐受毒性、患者撤回知情同意或研究者评估终止；达罗他胺可依据毒性调整剂量，戈舍瑞林不允许减量。 2 疗效与安全评估 肿瘤影像学评估：每8周复查CT/MRI；单药队列由研究者评估疗效，联合队列采用盲态独立中心阅片（ICR）判定靶病灶缓解； 不良反应：全程监测至末次给药后28天，依据CTCAE v5.0分级； 生活质量：采用EQ-5D-5L、EQ-VAS量表，基线、每周期、治疗结束时评估。 研究终点 1.主要终点：客观缓解率（ORR）； 2.次要终点：无进展生存期（PFS）、总生存期（OS）、缓解持续时间（DOR）、临床获益率CBR（CR/PR/≥24周稳定SD）、疾病控制率DCR（CR/PR/≥6周SD）、安全性、患者生活质量； 3.探索终点：AR表达水平、Ki-67指数与治疗应答的相关性，本地与中心AR检测一致性。 四、核心疗效数据 1 ORR 达罗他胺单药队列（n=24，FAS集）：研究者评估ORR仅8.3%（90%CI：1.5~24.0），仅2例达到PR，无CR；DCR 为54.2%，CBR为41.7%； 达罗他胺+戈舍瑞林联合队列（n=31，mFAS集）：中心独立阅片ORR高达45.2%（90%CI：29.7~61.3），成功达到研究预设疗效终点；包含1例CR、13例PR；DCR 64.5%，CBR 51.6%。 图1. 两队列肿瘤缩小瀑布图 瀑布图直观可见：联合队列超半数患者靶病灶最大径缩小超过30%，满足PR判定标准；单药队列仅极少数患者出现显著肿瘤退缩，单药抑瘤活性十分有限（图1）。 3 生存获益数据 单药队列的中位PFS为5.7个月（95%CI：1.9~15.2）；而联合队列的中位PFS为13.1个月（95%CI：2.0～未达到），无进展生存实现翻倍（图2）。 图2. PFS生存曲线 两组中位OS均未达到；12个月OS率单药队列为91.3%、联合队列为87.0%，整体长期生存预后良好（图3）。 图3. OS生存曲线 单药队列中位DOR为14.7个月；联合队列中位DOR延长至18.2个月，肿瘤缓解更持久。数据截止时，联合队列仍有39.4%（13例）患者持续治疗；单药队列全部患者均终止用药，疾病进展为主要停药原因。 3 亚组探索结果 1.联合方案获益不受既往系统治疗影响：5例既往接受抗HER2治疗患者中，3例PR、1例SD、1例PD； 2.未发现ORR与AR表达强度、Ki-67增殖指数存在明确关联；仅小样本提示AR表达＜70%患者无客观缓解，需扩大样本验证； 3.本地病理与中心病理AR检测一致性93.9%，临床常规IHC检测AR状态可靠性高。 五、安全耐受性与患者生活质量 两种内分泌方案整体耐受性良好，无任何治疗相关死亡，不良反应以1~2级轻度毒性为主： 单药队列（n=24）中，≥3级不良反应发生率37.5%；3例发生严重治疗相关不良事件（过敏性休克、药物性皮炎、横纹肌溶解）；特征性内分泌不良反应为男性乳房发育（20.8%）；4例剂量下调、6例短暂停药、3例永久终止治疗。 联合队列（n=33）中，≥3级不良反应仅18.2%，毒性显著优于单药组；仅3例可控严重不良反应（达罗他胺相关过敏发热、双药相关弥散性血管内凝血），无4/5级重度毒性；内分泌不良反应仅乏力（9.1%）、潮热（6.1%），无男性乳房发育（戈舍瑞林抑制睾酮生成，规避该不良反应）；仅1例达罗他胺减量，永久停药仅2例。 研究全程还采用EQ-5D-5L、EQ-VAS评估乐患者生活质量：联合队列EQ-VAS评分出现小幅改善，达到临床最小重要差异阈值；单药队列评分小幅波动，无持续性显著下降；EQ-5D所有功能维度均未观察到有临床意义的持续恶化，两种内分泌方案均可稳定维持晚期肿瘤患者生活质量。 六、研究讨论与临床启示 1 联合雄激素阻断疗效显著优于单纯AR抑制剂 从机制上看，单用达罗他胺仅阻断肿瘤细胞AR受体，会通过负反馈升高循环睾酮，残留雄激素持续激活通路；戈舍瑞林抑制性腺雄激素合成，从源头切断配体，叠加达罗他胺高亲和力受体拮抗，实现雄激素信号全通路阻断，这也是联合方案缓解率、PFS大幅提升的核心原因。 2 填补免化疗治疗空白，适配多类临床人群 晚期唾液腺癌传统以化疗为基础，但骨髓、消化道毒性限制长期使用；抗HER2治疗仅覆盖小部分人群。达罗他胺联合戈舍瑞林给药便捷（口服+每月皮下注射）、低毒、可长期维持，可作为免化疗姑息优选方案，尤其适合HER2阴性、高龄、合并基础疾病不耐受化疗、化疗后进展的AR阳性唾液腺癌患者。 3 研究客观局限性（临床解读需谨慎） 序贯非随机双队列设计，无法通过统计学直接证实联合方案优于单药；两组入组时段、基线病理亚型、既往治疗存在混杂因素； 入组人群以唾液导管癌为主，结论难以直接推广至其他罕见唾液腺病理亚型； 未前瞻性收集HER2分层数据，无法明确内分泌治疗与抗HER2药物的最优治疗序贯； AR低表达亚组样本量极小，暂无法确定最佳AR阳性临界值。 编后语 Ⅱ期DISCOVARY试验是全球首项前瞻性证实达罗他胺联合戈舍瑞林在AR阳性不可切除/复发转移唾液腺癌具备强效抗肿瘤活性的临床试验。单纯达罗他胺单药缓解率不足10%，临床价值有限；而达罗他胺联合戈舍瑞林联合雄激素阻断方案客观缓解率达45.2%，中位PFS翻倍，缓解持续时间更长，重度不良反应发生率更低。总之，该方案或可为这类罕见难治恶性肿瘤提供低毒免化疗新选择，有望重塑AR阳性晚期唾液腺癌的全身治疗策略，亟待Ⅲ期临床试验进一步验证其长期生存获益。 参考文献Okano S, Tahara M, Tsukahara K, Otsuka T, Kano S, Nagaoka M, Uryu H, Sano D, Nishio N, Ono K, Ohkoshi A, Hanazawa T, Shinoda S, Takeda Y, Yamamoto K, Kiyota N. Darolutamide Alone and in Combination With Goserelin in Androgen Receptor-Positive Salivary Gland Carcinoma: Results From the Phase II DISCOVARY Trial. J Clin Oncol. 2026 Aug 3:JCO2503028.  （来源：《肿瘤瞭望》编辑部） 声 明 凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息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，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。