創(chuàng)新放射性偶聯(lián)藥物有望今年獲批，新一代ADC迎來多項進展 | Bilingual

編者按：偶聯(lián)藥物通過將與靶蛋白結(jié)合的配體與功能性載荷連接，實現(xiàn)向特定組織或細胞精準遞送載荷的效果。近年來，這一領域快速發(fā)展，2025年，共有4款創(chuàng)新抗體偶聯(lián)藥物（ADC）獲得監(jiān)管機構批準上市。ADC之外，放射性偶聯(lián)藥物（RDC）、多肽偶聯(lián)藥物（PDC）等新興偶聯(lián)模式也不斷涌現(xiàn)。本文將盤點2026年第一季度偶聯(lián)領域的重要進展，并介紹藥明康德一體化CRDMO平臺賦能抗體偶聯(lián)藥物開發(fā)的能力。

兩款療法獲FDA優(yōu)先審評資格，ADC領域創(chuàng)新不斷

在2026年第一季度，由阿斯利康（AstraZeneca）和第一三共（Daiichi Sankyo）共同開發(fā)的兩款ADC的補充生物制品許可申請（sBLA）獲得美國FDA授予的優(yōu)先審評資格。其中，Trop2靶向抗體偶聯(lián)藥物Datroway（datopotamab deruxtecan）旨在用于治療不可切除或轉(zhuǎn)移性三陰性乳腺癌（TNBC）成人患者，這些患者不適合接受PD-1/PD-L1抑制劑治療。HER2靶向ADC Enhertu（trastuzumab deruxtecan）旨在作為手術之后的輔助療法，用于治療在接受新輔助治療之后，乳房和/或淋巴結(jié)仍存在殘留侵襲性疾病的HER2陽性早期乳腺癌患者。

此外，禮來（Eli Lilly and Company）開發(fā)的葉酸受體α（FRα）靶向ADC sofetabart mipitecan獲得FDA授予，用于治療既往接受過貝伐珠單抗和ADC療法mirvetuximab soravtansine的鉑耐藥性上皮性卵巢癌、輸卵管癌或原發(fā)性腹膜癌成年患者。

百利天恒與百時美施貴寶（Bristol Myers Squibb）聯(lián)合開發(fā)的靶向EGFR和HER3的潛在“first-in-class”雙特異性ADC izalontamab brengitecan（iza-bren），在既往接受過紫杉烷類藥物治療后疾病出現(xiàn)進展的三陰性乳腺癌患者中進行的3期臨床試驗獲得積極頂線結(jié)果。期中分析結(jié)果顯示，iza-bren達到了無進展生存期（PFS）和總生存期（OS）的雙重主要終點。

PDS Biotechnology公布了其在研白細胞介素-12（IL-12）腫瘤靶向免疫細胞因子PDS01ADC在一項2期臨床試驗中的研究結(jié)果。PDS01ADC將能夠與腫瘤內(nèi)壞死DNA結(jié)合的抗體與IL-12偶聯(lián)。該抗體能夠特異性靶向并將IL-12遞送至腫瘤內(nèi)部微環(huán)境，從而抑制腫瘤抵御T細胞攻擊的能力。同時，IL-12還可促進T細胞向腫瘤浸潤并激活T細胞。研究顯示，在晚期去勢抵抗性前列腺癌患者中，接受PDS01ADC與多西他賽聯(lián)合治療的患者的中位無進展生存期為9.6個月。此外，還觀察到具有潛力的前列腺特異性抗原（PSA）中位下降幅度為40%，在16名患者中，有6名患者PSA下降超過50%。

在這些臨床進展之外，多家開發(fā)新一代ADC的新銳公司完成融資或者達成研發(fā)合作。這些公司致力于通過不同策略，進一步改進ADC的安全性、有效性和腫瘤選擇性。例如，InduPro公司與禮來公司達成戰(zhàn)略研發(fā)合作，基于其專有平臺開發(fā)雙特異性或三特異性ADC或T細胞銜接器。InduPro的技術平臺能夠發(fā)現(xiàn)在腫瘤細胞表面與腫瘤相關抗原共同表達的腫瘤相關鄰近抗原（TAPA）。利用這一技術可以發(fā)現(xiàn)具有腫瘤特異性的創(chuàng)新靶點蛋白對，用于設計雙特異性ADC或多特異性T細胞銜接器，提高療法的安全性、效力和腫瘤選擇性。

今年完成1300萬美元種子輪融資的Fortitude Biomedicines專注于開發(fā)攜帶創(chuàng)新載荷的ADC。該公司的GLUE-DAC平臺將抗體與其獨有的分子膠載荷偶聯(lián)，整合ADC的精準靶向能力與分子膠的靶向蛋白降解能力，具有克服耐藥機制，解鎖創(chuàng)新靶點，以及擴展ADC治療窗口的潛力。

放射性偶聯(lián)藥物：創(chuàng)新療法有望今年獲批

ITM Isotope Technologies公布了在研放射性偶聯(lián)藥物（RDC）177Lu-edotreotide在3期臨床試驗COMPETE中的亞組分析結(jié)果。在生長抑素受體（SSTR）陽性的胰腺神經(jīng)內(nèi)分泌瘤患者（P-NETs）中，177Lu-edotreotide治療組的中位PFS為24.5個月，活性對照組為14.7個月。177Lu-edotreotide治療組的客觀緩解率為33.3%，活性對照組為3.6%。FDA已經(jīng)接受177Lu-edotreotide用于治療胃腸胰神經(jīng)內(nèi)分泌腫瘤的新藥申請，預計在今年8月28日之前完成審評。

ITM公司之外，Aktis Oncology公司今年通過IPO募集約3.65億美元，用于進一步推進其放射性偶聯(lián)藥物研發(fā)。公司擬將募集資金用于支持核心候選藥物AKY-1189（以錒-225為放射同位素）的1b期臨床研究，該藥物主要針對表達nectin-4的腫瘤患者。

Starget Pharma公司完成1800萬美元的A輪融資，加速基于其AI驅(qū)動藥物發(fā)現(xiàn)平臺設計的多肽放射性偶聯(lián)藥物的開發(fā)。

Curium Group、PeptiDream和PDRadiopharma公司共同宣布，在研療法177Lu-PSMA-I&T在日本進行的注冊性2期臨床試驗已經(jīng)完成首例患者給藥。177Lu-PSMA-I&T是一款靶向前列腺特異性膜蛋白（PSMA）的多肽放射性偶聯(lián)藥物，用于治療PSMA陽性轉(zhuǎn)移性去勢抵抗性前列腺癌患者。

一體化平臺助力創(chuàng)新抗體偶聯(lián)藥物開發(fā)

在抗體偶聯(lián)藥物持續(xù)迭代的過程中，開發(fā)具有更高效力和差異化作用機制的創(chuàng)新載荷已成為推動下一代ADC突破的重要方向。然而，創(chuàng)新載荷往往具有高活性、復雜代謝路徑以及獨特體內(nèi)行為，對藥物代謝與藥代動力學（DMPK）研究提出了更高要求。依托完善的DMPK研究體系與豐富的ADC研究經(jīng)驗，藥明康德DMPK可在早期階段開展針對創(chuàng)新載荷開發(fā)的一系列關鍵體外與體內(nèi)研究，以全面解析載荷的ADME特征并降低后續(xù)開發(fā)風險。

例如，在體外研究方面，可開展低濃度條件下的血漿蛋白結(jié)合（PPB）評估、代謝穩(wěn)定性與代謝物鑒定、藥物代謝酶表型研究以及轉(zhuǎn)運體相關研究，從而系統(tǒng)解析載荷在體內(nèi)的代謝途徑、潛在藥物相互作用風險及組織分布機制。在體內(nèi)研究方面，通過放射性標記技術結(jié)合定量全身放射自顯影（QWBA）等方法，可深入研究載荷的組織分布、排泄路徑及質(zhì)量平衡特征，并評估其在體內(nèi)的清除能力。此外，針對ADC療效主要由載荷在腫瘤組織中的暴露驅(qū)動的特點，藥明康德還可開展腫瘤組織藥代與PK/PD研究，系統(tǒng)評估腫瘤內(nèi)載荷暴露與抗腫瘤活性之間的關系。

通過整合多維度生物分析技術與體內(nèi)外研究體系，藥明康德DMPK團隊能夠為創(chuàng)新ADC載荷的篩選、結(jié)構優(yōu)化及安全性評價提供關鍵數(shù)據(jù)支持，加速具有新機制載荷的開發(fā)與轉(zhuǎn)化，并持續(xù)賦能下一代ADC藥物的創(chuàng)新研發(fā)。

Innovative Radiopharmaceutical Conjugates May Gain Approval This Year; Next-Generation ADCs See Multiple Advances

Conjugated therapeutics achieve targeted delivery of functional payloads to specific tissues or cells by linking ligands that bind target proteins with therapeutic cargos. In recent years, this field has advanced rapidly. In 2025, four innovative antibody-drug conjugates (ADCs) received regulatory approval. Beyond ADCs, emerging conjugate modalities such as radiopharmaceutical drug conjugates (RDCs), peptide-drug conjugates (PDCs), and oligonucleotide conjugates have also continued to emerge. This article reviews key developments in the conjugate therapeutics field in the first quarter of 2026 and introduces how WuXi AppTec’s integrated CRDMO platform enables the development of antibody-drug conjugates.

Two therapies receive FDA Priority Review as ADC innovation continues

In the first quarter of 2026,supplemental biologics license applications (sBLAs) for two ADCs jointly developed by AstraZeneca and Daiichi Sankyo were granted Priority Review by the U.S. Food and Drug Administration (FDA).

Among them, the TROP2-targeting ADC Datroway (datopotamab deruxtecan) is intended for the treatment of adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who are not eligible to receive PD-1/PD-L1 inhibitor therapy. The HER2-targeted ADC Enhertu (trastuzumab deruxtecan) is intended as an adjuvant therapy after surgery for patients with HER2-positive early breast cancer who have residual invasive disease in the breast and/or lymph nodes following neoadjuvant treatment.

In addition,the folate receptor-alpha (FRα)-targeting ADC sofetabart mipitecan developed by Eli Lilly and Company received Breakthrough Therapy Designation from the FDAfor the treatment of adult patients with platinum-resistant epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who have previously received bevacizumab and the ADC mirvetuximab soravtansine.

The potential first-in-class bispecific ADC izalontamab brengitecan (iza-bren), targeting EGFR and HER3 and jointly developed by SystImmune and Bristol Myers Squibb, achieved positive topline results in a Phase 3 clinical trial in patients with triple-negative breast cancer whose disease progressed after prior taxane therapy. An interim analysis showed that iza-bren met its dual primary endpoints of progression-free survival (PFS) and overall survival (OS).

PDS Biotechnology Corporation announced results from a Phase 2 clinical study of its investigational Interleukin-12 (IL-12) tumor-targeted immunocytokine PDS01ADC.PDS01ADC conjugates IL-12 with an antibody capable of binding to necrotic DNA within tumors. This antibody can specifically target and deliver IL-12 into the inner tumor microenvironment, thereby suppressing the tumor’s ability to protect itself from T-cell attack.At the same time, IL-12 also promotes T-cell infiltration into the tumor and activates T cells.

The study showed that in patients with advanced castration-resistant prostate cancer, the median progression-free survival for patients receiving the combination of PDS01ADC and docetaxel was 9.6 months. In addition, a promising median decline in prostate-specific antigen (PSA) of 40% was observed, with 6 of 16 patients achieving a PSA reduction of more than 50%.

Beyond these clinical advances, several emerging companies focused on developing next-generation ADCs completed financing rounds or established R&D collaborations. These companies aim to further improve the safety, efficacy, and tumor selectivity of ADCs through various strategies. For example, InduPro entered into a strategic research collaboration with Eli Lilly to develop bispecific or trispecific ADCs or T-cell engagers based on its proprietary platform. InduPro’s technology platform identifies tumor-associated proximity antigens (TAPAs) that are co-expressed with tumor-associated antigens on tumor cell surfaces. This approach enables the discovery of tumor-specific target protein pairs for the design of bispecific ADCs or multispecific T-cell engagers, improving the safety, potency, and tumor selectivity of therapies.

Fortitude Biomedicines, which recently completed a $13 million seed financing round, is focused on developing ADCs carrying novel payloads. Its GLUE-DAC platform conjugates antibodies with proprietary molecular-glue payloads, integrating the precise targeting capability of ADCs with the targeted protein degradation capability of molecular glues. This approach has the potential to overcome resistance mechanisms, unlock novel targets, and expand the therapeutic window of ADCs.

Radiopharmaceutical drug conjugates: innovative therapies may gain approval this year

ITM Isotope Technologies Munich reported subgroup analysis results from the Phase 3 COMPETE trial of the investigational radiopharmaceutical drug conjugate (RDC) 177Lu-edotreotide. In patients with somatostatin receptor (SSTR)-positive pancreatic neuroendocrine tumors (P-NETs), the median PFS was 24.5 months in the 177Lu-edotreotide treatment group compared with 14.7 months in the active control group. The objective response rate was 33.3% in the treatment group versus 3.6% in the active control group.The FDA has accepted the new drug application for 177Lu-edotreotide for the treatment of gastroenteropancreatic neuroendocrine tumors, with a review decision expected by August 28 this year.

In addition to ITM, Aktis Oncology raised approximately $365 million through an IPO this year to further advance its radiopharmaceutical drug development programs. The company plans to use the proceeds to support the Phase 1b clinical study of its lead candidate AKY-1189, which uses actinium-225 as the radioisotope and targets tumors expressing nectin-4.

Starget Pharma completed an $18 million Series A financing to accelerate the development of peptide radiopharmaceutical drug conjugates designed using its AI-driven drug discovery platform.

Curium Group, PeptiDream, and PDRadiopharma jointly announced that the first patient has been dosed in a registrational Phase 2 clinical trial in Japan evaluating the investigational therapy 177Lu-PSMA-I&T. This peptide radiopharmaceutical drug conjugate targets prostate-specific membrane antigen (PSMA) and is intended for the treatment of patients with PSMA-positive metastatic castration-resistant prostate cancer.

Integrated Platform Enables the Development of Innovative ADCs

As ADCs continue to evolve, the development of novel payloads with greater potency and differentiated mechanisms of action has become a key driver for next-generation ADC innovation. However, these innovative payloads often exhibit high biological activity, complex metabolic pathways, and unique in vivo behaviors, placing greater demands on drug metabolism and pharmacokinetics (DMPK) evaluation. Leveraging its comprehensive DMPK research platform and extensive experience in ADC development, WuXi AppTec provides a range of critical in vitro and in vivo studies to support the early development of novel ADC payloads and to systematically characterize their ADME properties while mitigating downstream development risks.

For in vitro studies, WuXi AppTec DMPK can conduct plasma protein binding (PPB) assays at low payload concentrations that better reflect in vivo exposure levels, along with metabolic stability assessment, metabolite identification, drug-metabolizing enzyme phenotyping, and transporter interaction studies. These evaluations help elucidate payload metabolic pathways, potential drug–drug interaction risks, and mechanisms governing tissue distribution. For in vivo studies, radiolabeled payload approaches combined with techniques such as quantitative whole-body autoradiography (QWBA) can be applied to investigate tissue distribution, excretion pathways, and mass balance, providing a comprehensive understanding of payload disposition and clearance. In addition, given that ADC efficacy is largely driven by payload exposure within tumor tissues, WuXi AppTec can perform tumor pharmacokinetics and PK/PD studies in relevant animal models to evaluate the relationship between intratumoral payload exposure and antitumor activity.

By integrating multidimensional bioanalytical capabilities with robust in vitro and in vivo DMPK study systems, WuXi AppTec enables partners to generate critical insights for payload screening, structural optimization, and safety evaluation, ultimately accelerating the development and translation of next-generation ADCs with innovative payload mechanisms.

參考資料：

[1] CrossPoint, pre-A 3.6 billion... FC Cyclizing 'EGFR ADC' Development. Retrieved March 25, 2026, from https://www.biospectator.com/news/view/27973

[2] MediLink Has Signed an Additional Exclusive Licensing Agreement with Roche. Retrieved January 9, 2026, from https://www.prnewswire.com/news-releases/medilink-has-signed-an-additional-exclusive-licensing-agreement-with-roche-302656495.html

[3] Aktis Oncology Announces Closing of Upsized Initial Public Offering and Full Exercise of Underwriters’ Option to Purchase Additional Shares. Retrieved March 25, 2026, from https://investors.aktisoncology.com/news-releases/news-release-details/aktis-oncology-announces-closing-upsized-initial-public-offering

[4] PDS Biotech Announces Presentation of Preliminary Results from Phase 2 Study of IL-12 Tumor Targeted Immunocytokine (PDS01ADC) in 3rd Line Metastatic Castration Resistant Prostate Cancer by the NCI. Retrieved March 25, 2026, from https://www.globenewswire.com/news-release/2026/01/28/3227632/37149/en/PDS-Biotech-Announces-Presentation-of-Preliminary-Results-from-Phase-2-Study-of-IL-12-Tumor-Targeted-Immunocytokine-PDS01ADC-in-3rd-Line-Metastatic-Castration-Resistant-Prostate-Ca.html

[5] Lilly's sofetabart mipitecan receives U.S. FDA's Breakthrough Therapy designation for the treatment of certain patients with platinum-resistant ovarian cancer. Retrieved March 25, 2026, from https://www.prnewswire.com/news-releases/lillys-sofetabart-mipitecan-receives-us-fdas-breakthrough-therapy-designation-for-the-treatment-of-certain-patients-with-platinum-resistant-ovarian-cancer-302665319.html

[6] GlycoNex Inc. and Nippon Kayaku Co., Ltd. Enter Collaboration to Advance Next-Generation ADC Candidate GNX201-ADC. Retrieved March 25, 2026, from https://www.prnewswire.com/news-releases/glyconex-inc-and-nippon-kayaku-co-ltd-enter-collaboration-to-advance-next-generation-adc-candidate-gnx201-adc-302721456.html

[7] ENHERTU? (fam-trastuzumab deruxtecan-nxki) granted Priority Review in the US as post-neoadjuvant treatment for patients with HER2-positive early breast cancer. Retrieved March 25, 2026, from https://www.biospace.com/press-releases/enhertu-fam-trastuzumab-deruxtecan-nxki-granted-priority-review-in-the-us-as-post-neoadjuvant-treatment-for-patients-with-her2-positive-early-breast-cancer

[8] SystImmune and Bristol Myers Squibb Highlight Positive Phase III Interim Topline Results for izalontamab brengitecan (Iza-bren) in Previously Treated Unresectable Locally Advanced or Metastatic Triple-Negative Breast Cancer. Retrieved March 25, 2026, from https://www.biospace.com/press-releases/systimmune-and-bristol-myers-squibb-highlight-positive-phase-iii-interim-topline-results-for-izalontamab-brengitecan-iza-bren-in-previously-treated-unresectable-locally-advanced-or-metastatic-triple-negative-breast-cancer

[9] DATROWAY? (datopotamab deruxtecan-dlnk) granted Priority Review in the US as 1st-line treatment for patients with metastatic triple-negative breast cancer who are not candidates for immunotherapy. Retrieved March 25, 2026, from https://www.biospace.com/press-releases/datroway-datopotamab-deruxtecan-dlnk-granted-priority-review-in-the-us-as-1st-line-treatment-for-patients-with-metastatic-triple-negative-breast-cancer-who-are-not-candidates-for-immunotherapy

[10] Blue Earth Diagnostics Announces Positive Results from Head-to-Head Comparator Study of POSLUMA? (Flotufolastat F 18) and Piflufolastat F 18 Urinary Bladder Radioactivity in Men with Biochemical Recurrence of Prostate Cancer. Retrieved March 25, 2026, from https://www.prnewswire.com/news-releases/blue-earth-diagnostics-announces-positive-results-from-head-to-head-comparator-study-of-posluma-flotufolastat-f-18-and-piflufolastat-f-18-urinary-bladder-radioactivity-in-men-with-biochemical-recurrence-of-prostate-cancer-302699152.html

[11] Curium Group, PeptiDream and PDRadiopharma Enroll First Patient to Registrational Clinical Trial of Lu-PSMA-I&T for Prostate Cancer in Japan. Retrieved March 25, 2026, from https://www.globenewswire.com/news-release/2026/02/04/3231755/0/en/Curium-Group-PeptiDream-and-PDRadiopharma-Enroll-First-Patient-to-Registrational-Clinical-Trial-of-Lu-PSMA-I-T-for-Prostate-Cancer-in-Japan.html

[12] AdvanCell Announces Collaboration and Exclusive Licensing Agreement with 48Hour Discovery to Develop a Novel Peptide-Based Lead-212 Radiotherapeutic for a Gastrointestinal Cancer with Significant Medical Need. Retrieved March 25, 2026, from https://www.biospace.com/press-releases/advancell-announces-collaboration-and-exclusive-licensing-agreement-with-48hour-discovery-to-develop-a-novel-peptide-based-lead-212-radiotherapeutic-for-a-gastrointestinal-cancer-with-significant-medical-need

[13] Avacta Announces U.S. Food and Drug Administration Clearance of the Investigational New Drug (IND) Application for the Second pre|CISION? Medicine, FAP-Exatecan (AVA6103). Retrieved March 25, 2026, from https://www.globenewswire.com/news-release/2026/01/21/3222755/0/en/Avacta-Announces-U-S-Food-and-Drug-Administration-Clearance-of-the-Investigational-New-Drug-IND-Application-for-the-Second-pre-CISION-Medicine-FAP-Exatecan-AVA6103.html

[14] Rakuten Medical Raises $100 Million in Oversubscribed Series F to Accelerate Development Toward U.S. Regulatory Approval. Retrieved March 25, 2026, from https://www.prnewswire.com/news-releases/rakuten-medical-raises-100-million-in-oversubscribed-series-f-to-accelerate-development-toward-us-regulatory-approval-302655158.html

[15] InduPro Therapeutics Announces Strategic Collaboration with Lilly to Develop First-in-Class Bispecific/Multispecific Oncology Therapeutics Using InduPro’s Proximity-Guided Platform. Retrieved March 25, 2026, from https://www.businesswire.com/news/home/20260107870601/en/InduPro-Therapeutics-Announces-Strategic-Collaboration-with-Lilly-to-Develop-First-in-Class-BispecificMultispecific-Oncology-Therapeutics-Using-InduPros-Proximity-Guided-Platform

[16] TwoStep Therapeutics to Present at the Novel Conjugates Summit 2026. Retrieved March 25, 2026, from https://twosteptx.com/news/twostep-therapeutics-to-present-at-the-novel-conjugates-summit-2026/

[17] Fortitude Biomedicines Launches With $13M in Financing to Advance Novel Antibody-based Therapies for Treatment of Autoimmune Diseases and Cancer. Retrieved March 25, 2026, from https://www.biospace.com/press-releases/fortitude-biomedicines-launches-with-13m-in-financing-to-advance-novel-antibody-based-therapies-for-treatment-of-autoimmune-diseases-and-cancer

[18] Starget Pharma Closes $18M Series A Financing and Announces Strategic Collaboration with Center for Molecular Imaging and Therapy in Louisiana. Retrieved March 25, 2026, from https://www.prnewswire.com/news-releases/starget-pharma-closes-18m-series-a-financing-and-announces-strategic-collaboration-with-center-for-molecular-imaging-and-therapy-in-louisiana-302691872.html

[19] Kodiak Sciences Announces Positive Topline Results in GLOW2, the Second Phase 3 Study in Diabetic Retinopathy, Demonstrating Superiority of Zenkuda? (tarcocimab tedromer) Over Sham. Retrieved April 6, 2026, from https://www.prnewswire.com/news-releases/kodiak-sciences-announces-positive-topline-results-in-glow2-the-second-phase-3-study-in-diabetic-retinopathy-demonstrating-superiority-of-zenkuda-tarcocimab-tedromer-over-sham-302725841.html

免責聲明：本文僅作信息交流之目的，文中觀點不代表藥明康德立場，亦不代表藥明康德支持或反對文中觀點。本文也不是治療方案推薦。如需獲得治療方案指導，請前往正規(guī)醫(yī)院就診。

版權說明：歡迎個人轉(zhuǎn)發(fā)至朋友圈，謝絕媒體或機構未經(jīng)授權以任何形式轉(zhuǎn)載至其他平臺。轉(zhuǎn)載授權請在「藥明康德」微信公眾號回復“轉(zhuǎn)載”，獲取轉(zhuǎn)載須知。