新型組合療法讓100%這類肺癌患者腫瘤明顯縮小或消退！今年第三季度，這類創(chuàng)新療法還有哪些新進(jìn)展？

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(xì)胞精準(zhǔn)遞送載荷的效果。近年來，這一領(lǐng)域快速發(fā)展，據(jù)統(tǒng)計，2024年全球啟動了284項抗體偶聯(lián)藥物（ADC）臨床試驗，比2023年增加了100多項，彰顯了偶聯(lián)藥物領(lǐng)域的迅猛增長。ADC之外，放射性偶聯(lián)藥物（RDC）、多肽偶聯(lián)藥物（PDC）以及寡核苷酸偶聯(lián)藥物等新興偶聯(lián)模式也不斷涌現(xiàn)。藥明康德旗下WuXi TIDES搭建了為寡核苷酸、多肽及復(fù)雜化學(xué)偶聯(lián)藥物開發(fā)提供一體化服務(wù)的CRDMO平臺，覆蓋從藥物發(fā)現(xiàn)、CMC開發(fā)及商業(yè)化生產(chǎn)的全生命周期，尤其借助藥明康德在化學(xué)業(yè)務(wù)方面的豐富經(jīng)驗，為賦能新一代偶聯(lián)療法奠定了堅實基礎(chǔ)。本文將盤點2025年第三季度（Q3）偶聯(lián)領(lǐng)域的最新進(jìn)展，并介紹WuXi TIDES一體化CRDMO平臺賦能多肽偶聯(lián)藥物開發(fā)的能力。

抗體偶聯(lián)藥物：多款療法獲FDA突破性療法認(rèn)定，雙特異性ADC嶄露頭角

2025年第三季度，多款創(chuàng)新ADC獲得FDA授予的突破性療法認(rèn)定，這一認(rèn)定旨在加快治療嚴(yán)重疾病創(chuàng)新療法的開發(fā)和審評，初步臨床證據(jù)顯示它們與已有療法相比在具有臨床意義的終點方面提供顯著改善。

獲得突破性療法認(rèn)定的ADCs既包括已獲批的重磅藥物，也涵蓋靶向新靶點的潛在“first-in-class”療法，還包括一款雙特異性ADC。這也是雙特異性ADCs首次獲得FDA授予的突破性療法認(rèn)定。

▲2025年第三季度獲得FDA突破性療法認(rèn)定的ADCs（數(shù)據(jù)來源：公開資料，截至9月22日）

雙特異性ADCs通過靶向兩個不同靶點，或者同一靶點上的兩個不同表位，與只與單個靶點接合的ADCs相比，可能增加與靶細(xì)胞接合的特異性，從而提高療效并降低脫靶效應(yīng)帶來的潛在毒性。此外，靶向不同靶點蛋白可能讓雙特異性ADCs與更為廣泛的細(xì)胞群體結(jié)合，從而克服腫瘤的異質(zhì)性。

這一領(lǐng)域正在得到業(yè)界越來越多的關(guān)注，在2025年Q3，多家公司在雙特異性ADC領(lǐng)域取得進(jìn)展。例如，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在治療鼻咽癌的3期臨床試驗中，中期分析達(dá)到主要終點。在今年9月的世界肺癌大會（WCLC）上公布的數(shù)據(jù)顯示，劑量為2.5 mg/kg的izalontamab brengitecan與EGFR抑制劑Tagrisso作為一線組合療法，在治療攜帶EGFR突變的非小細(xì)胞肺癌（NSCLC）患者的2期臨床試驗中，達(dá)到100%的客觀緩解率（ORR）和95%的確認(rèn)ORR，12個月無進(jìn)展生存率為92.1%。

圖片來源： 123RF

康方生物的AK146D1是一款靶向Trop2和Nectin4的雙特異性ADC，它在今年7月完成1a期臨床試驗的首例患者給藥。Avenzo Therapeutics和映恩生物聯(lián)合開發(fā)的EGFR/HER3靶向ADC AVZO-1418也完成1/2期臨床試驗的首位患者給藥，用于治療晚期實體瘤。

天演藥業(yè)與ConjugateBio公司在今年7月達(dá)成研發(fā)合作，ConjugateBio將利用天演藥業(yè)開發(fā)的獨有雙特異性抗體進(jìn)行雙特異性ADC項目的開發(fā)。Radiance Biopharma則在9月與科弈藥業(yè)達(dá)成研發(fā)和許可合作，共同開發(fā)潛在“first-in-class”靶向c-MET和EGFR的在研ADC RB-601（KY-0301）。

在Q3 2025，多款靶向單一靶點的創(chuàng)新ADC也獲得積極臨床進(jìn)展。例如，默沙東（MSD）與第一三共（Daiichi Sankyo）聯(lián)合開發(fā)的B7-H3靶向ADC ifinatamab deruxtecan在治療廣泛期小細(xì)胞肺癌（ES-SCLC）的2期臨床試驗中表現(xiàn)出48%的確認(rèn)ORR和87.6%的疾病控制率（DCR）。

由PD-1抑制劑Keytruda與抗體偶聯(lián)藥物Padcev構(gòu)成的組合療法，作為圍手術(shù)治療方案，在治療患有肌層浸潤性膀胱癌（MIBC）且不適合使用以順鉑為基礎(chǔ)化療的患者的3期臨床試驗中，與單純手術(shù)相比，在主要終點無事件生存期（EFS），以及關(guān)鍵次要終點總生存期（OS）和完全病理學(xué)緩解率（pCR）方面均取得了具有統(tǒng)計學(xué)意義和臨床意義的改善。

BioNTech和映恩生物聯(lián)合開發(fā)的HER2靶向ADC trastuzumab pamirtecan在治療經(jīng)治HER2陽性乳腺癌的關(guān)鍵性3期臨床試驗中，與活性對照ADC相比，在預(yù)定的期中分析中達(dá)到無進(jìn)展生存期的主要終點。

多家偶聯(lián)藥物新銳完成融資，放射性偶聯(lián)藥物備受關(guān)注

2025年第三季度，偶聯(lián)藥物領(lǐng)域的多家新銳陸續(xù)完成融資，為持續(xù)推動這一治療模式的創(chuàng)新提供了強(qiáng)勁動力。其中，放射性偶聯(lián)藥物公司的表現(xiàn)尤其亮眼，在第三季度至少有7家專注于RDC藥物開發(fā)的公司完成融資。例如ARTBIO在7月底宣布完成1.32億美元B輪融資，獲得資金將用于加速公司α粒子放射性配體療法的開發(fā)進(jìn)程。其針對轉(zhuǎn)移性去勢抵抗性前列腺癌的候選藥物AB001已進(jìn)入臨床開發(fā)階段。

▲2025年第三季度偶聯(lián)藥物領(lǐng)域部分投融資活動（數(shù)據(jù)來源：公開資料，截至9月22日）

雖然RDC在早期腫瘤成像和治療方面均展現(xiàn)巨大潛力，但其藥物結(jié)構(gòu)復(fù)雜，通常由靶向配體、連接子、螯合劑和放射性同位素組成。其生產(chǎn)過程需要多學(xué)科的專業(yè)技術(shù)支持。藥明康德綜合性的放射性藥物發(fā)現(xiàn)平臺整合了多肽發(fā)現(xiàn)和放射性藥物開發(fā)能力，提供包括多肽合成、螯合劑合成、放射性標(biāo)記、成像、藥理學(xué)研究和監(jiān)管申報支持等完善的服務(wù)。一體化平臺讓多個團(tuán)隊并行攻堅、高度協(xié)作，幫助合作伙伴快速推動RDC項目，節(jié)省寶貴的開發(fā)時間。藥明康德旗下WuXi TIDES CRDMO平臺目前正在賦能各類偶聯(lián)藥物開發(fā)，覆蓋多種疾病領(lǐng)域。

回顧2025年第三季度，偶聯(lián)藥物領(lǐng)域在臨床進(jìn)展以及投融資方面都取得了可圈可點的進(jìn)展。期待隨著偶聯(lián)技術(shù)的持續(xù)創(chuàng)新和優(yōu)化，催生更多造福患者的突破。WuXi TIDES團(tuán)隊將繼續(xù)利用其一體化的CRDMO平臺賦能偶聯(lián)藥物的開發(fā)，幫助合作伙伴將科學(xué)創(chuàng)新早日轉(zhuǎn)化成讓全球患者獲益的療法。

CRDMO: Q3 2025 Review of Conjugated Therapeutics

Conjugated drugs enable the precise delivery of therapeutic payloads to specific tissues or cells by linking target-binding ligands with functional payloads. In recent years, this field has advanced rapidly. According to a recent report, 284 antibody-drug conjugate (ADC) clinical trials were initiated globally in 2024—over 100 more than in 2023. Alongside ADCs, new conjugated modalities have also gained momentum, including radionuclide drug conjugates (RDCs), peptide-drug conjugates (PDCs), and oligonucleotide-drug conjugates. This growing momentum underscores the expanding potential of conjugated therapeutics in addressing a broad range of diseases.

Backed by extensive experience in chemistry and integrated drug development expertise, WuXi TIDES is supporting next-generation conjugated therapies. As an integral part of WuXi AppTec, WuXi TIDES has built an integrated CRDMO platform focused on oligonucleotides, peptides and related synthetic conjugates. This platform simplifies TIDES drug development by providing all discovery, CMC development and the entire manufacturing supply chain under one roof.

Antibody-Drug Conjugates: Multiple Therapies Receive FDA Breakthrough Therapy Designation

In the third quarter of 2025, several innovative ADCs received Breakthrough Therapy designation (BTD). This designation is intended to expedite the development and review of treatments for serious diseases when preliminary clinical evidence indicates a substantial improvement on clinically meaningful endpoints over available therapies.

Among the ADCs granted BTD are an approved blockbuster medicine, potential "first-in-class" therapies that target novel antigens, and one ADC designed to engage two antigens. Notably, this quarter marks the first time the FDA has awarded BTD to a bispecific ADC.

Bispecific ADCs can engage two distinct targets—or two different epitopes on the same target—thereby increasing tumor-cell binding specificity relative to single-target ADCs. This enhanced selectivity may translate into improved efficacy and reduced off-target toxicity. In addition, by recognizing different antigens, bispecific ADCs may address a broader spectrum of tumor cells, helping to overcome intratumoral heterogeneity.

Reflecting the growing interest in this modality, several bispecific ADC programs reported progress during Q3 2025. For example, izalontamab brengitecan, a potential "first-in-class" EGFR/HER3-targeting bispecific ADC, met the primary endpoint at interim analysis in a Phase 3 trial for nasopharyngeal carcinoma. Data presented at the World Conference on Lung Cancer (WCLC) in September also showed that izalontamab brengitecan at a dose of 2.5 mg/kg, combined with Tagrisso as a first-line therapy, achieved an objective response rate (ORR) of 100% and a confirmed ORR of 95% in a Phase 2 trial for patients with EGFR-mutant non-small cell lung cancer (NSCLC), with a 12-month progression-free survival (PFS) rate of 92.1%.

In addition, a Trop2/Nectin-4 bispecific ADC and an EGFR/HER3-targeting ADC both completed the dosing of first patients in their first-in-human clinical trials.

In July, Adagene entered into an R&D collaboration with ConjugateBio, under which ConjugateBio will leverage Adagene’s proprietary bispecific antibodies to develop bispecific ADC programs. In September, Radiance Biopharma reached a research and licensing collaboration with Novatim Immune Therapeutics to jointly develop RB-601 (KY-0301), a potential "first-in-class" investigational ADC targeting c-MET and EGFR.

In Q3 2025, several innovative single-target ADCs also achieved encouraging clinical progress. For example, ifinatamab deruxtecan, a B7-H3-targeted ADC, demonstrated a confirmed ORR of 48% and a disease control rate (DCR) of 87.6% in a Phase 2 trial for extensive-stage small cell lung cancer (ES-SCLC).

The combination therapy of the PD-1 inhibitor Keytruda with the ADC Padcev, as a perioperative treatment, showed statistically and clinically meaningful improvements compared with surgery alone in a Phase 3 trial in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-based chemotherapy. The improvements were seen in the primary endpoint event-free survival (EFS), as well as the key secondary endpoints overall survival (OS) and pathologic complete response (pCR).

Finally, trastuzumab pamirtecan, a HER2-targeted ADC, met the primary endpoint of progression-free survival in a pre-specified interim analysis of a pivotal Phase 3 trial in previously treated HER2-positive breast cancer, compared with an active control ADC.

Sustained Innovation: Emerging Players Secure New Financing

In Q3 2025, several emerging companies in the conjugate-therapy space completed new financing rounds, supporting continued innovation in this modality.

Financing activities in RDC developers were especially prominent during Q3 2025, with at least seven companies completing rounds ranging from seed to Series C+, reflecting investors’ interest in different stages of RDC companies. Targeted alpha-particle therapies (TAT) continue to emerge as a focal point. TAT leverages the unique properties of alpha particles—such as high linear energy transfer (LET) and short tissue penetration—to deliver potent cytotoxic effects to cancer cells while minimizing damage to surrounding healthy tissue.

Although RDCs have demonstrated potential in early tumor imaging and treatment, their complex drug structures—typically composed of a targeting ligand, linker, chelator, and radionuclide—require multidisciplinary technical expertise for development and manufacturing. WuXi AppTec offers a comprehensive radiopharmaceutical discovery platform that combines peptide discovery with radiopharmaceutical development, covering peptide synthesis, chelator synthesis, radiolabeling, imaging, pharmacology studies, and regulatory filing support. This integrated model enables parallel, highly collaborative efforts across multiple teams, helping partners accelerate RDC programs and save valuable development time.

In summary, Q3 2025 has seen remarkable progress in the conjugated drug field across clinical milestones and financing activities. As innovation and optimization in conjugation technologies advance, the field is poised for even more breakthroughs that promise to benefit patients worldwide.

WuXi TIDES remains committed to harnessing its fully integrated CRDMO platform to support the development of conjugated drugs—empowering partners to accelerate the translation of scientific innovation into transformative therapies.

參考資料：

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[18] BioNTech and DualityBio Announce Phase 3 Trial of ADC Candidate BNT323/DB-1303 Met Primary Endpoint of Progression Free Survival in HER2-Positive Metastatic or Unresectable Breast Cancer. Retrieved September 8, 2025, from https://investors.biontech.de/news-releases/news-release-details/biontech-and-dualitybio-announce-phase-3-trial-adc-candidate

[19] Radiance Biopharma Signs Exclusive License For ‘First In Class’ c-Met/EGFR Targeted Nano Antibody ADC. Retrieved September 8, 2025, from https://www.globenewswire.com/news-release/2025/09/03/3144055/0/en/Radiance-Biopharma-Signs-Exclusive-License-For-First-In-Class-c-Met-EGFR-Targeted-Nano-Antibody-ADC.html

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[21] Iza-bren and osimertinib combination shows 100% response rate in EGFR-mutated lung cancer. Retrieved September 8, 2025, from https://newsatw.com/iza-bren-and-osimertinib-combination-shows-100-response-rate-in-egfr-mutated-lung-cancer/

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