At the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, antibody–drug conjugates (ADCs) took center stage, not merely as incremental innovations but as a therapeutic class on the verge of redefining modern oncology. Across multiple sessions — from AstraZeneca’s presidential symposium to Merck’s and Bristol Myers Squibb’s early-phase showcases — ADCs demonstrated efficacy levels once reserved for targeted therapies or immuno-oncology breakthroughs. Response rates exceeding 50% in refractory populations, survival curves separating within months, and even signs of curative potential in early-stage disease signaled that the modality had reached a new clinical and technological maturity.
What distinguished ESMO 2025 was not only the number of ADC presentations, but also the consistency of their outcomes and the global scope of their development. Western pharmaceutical leaders and Chinese biotech innovators now appear in the same datasets, their compounds competing and collaborating on equal footing. From Enhertu’s paradigm-shifting success in curative-intent breast cancer, to SystImmune and BMS’s bispecific breakthrough in lung cancer, to Merck’s data-driven transformation of its post-Keytruda pipeline, the message was clear: the ADC field has entered a phase of clinical validation, industrial consolidation, and global convergence.
1. From Control to Cure – The Enhertu Turning Point
At the ESMO 2025 in Berlin, ADCs made a decisive leap from disease control to potential cure.
The defining moment came when AstraZeneca and Daiichi Sankyo presented late-phase data for trastuzumab deruxtecan (Enhertu) in early-stage HER2-positive breast cancer. These studies did not simply add another efficacy metric — they redefined what is clinically possible for ADCs.
In the Phase 3 DESTINY-Breast05 trial, Enhertu reduced the risk of invasive disease recurrence or death by 53% compared with Roche’s Kadcyla, marking a significant efficacy difference between two active ADCs in the adjuvant setting.
This improvement in invasive disease–free survival means that Enhertu achieved roughly another 50% reduction in recurrences beyond what Kadcyla had already prevented — a clinically transformative difference in a population previously considered “post-curative.”
The companion DESTINY-Breast11 trial confirmed that efficacy extends even earlier, before surgery.
Among approximately 640 high-risk, HER2-positive patients in the interim analysis of the Phase 3 DESTINY-Breast11 trial, the treatment regimen consisting of Enhertu followed by taxane plus Herceptin and Perjeta achieved a pCR rate of 67% versus 56% with standard anthracycline-based therapy.
Because pCR correlates strongly with long-term survival in HER2-positive disease, this 11% gain signals that the ADC may not only delay relapse but increase the proportion of patients functionally cured after neoadjuvant therapy. Two-year event-free survival already favored Enhertu (97% vs 93%) despite data still maturing.
2. Dual-Target Innovation – The Rise of Iza-bren
While Enhertu redefined ADC outcomes, iza-bren illustrated how next-generation engineering and cross-border collaboration are transforming their design logic. Developed jointly by SystImmune and Bristol Myers Squibb, the bispecific ADC simultaneously targets EGFR and HER3, two receptors that frequently drive resistance in lung and other epithelial cancers.
The global Phase 1 US-Lung-101 study enrolled 107 patients with refractory solid tumors.
At the 2.5 mg/kg dose administered on Days 1 and 8 of a three-week cycle, the trial achieved a 55% confirmed overall response rate (cORR) and a median progression-free survival (PFS) of 5.4 months. In heavily pre-treated populations where typical response rates fall below 20%, such figures indicate that bispecific targeting can overcome both oncogenic escape and prior TKI resistance, and the drug may transcend genotypic boundaries.
Equally important was the absence of interstitial lung disease (ILD) — a toxicity that has limited earlier DXd-based ADCs. By achieving high activity without pulmonary compromise, iza-bren provided proof that rational linker and payload design can decouple efficacy from dose-limiting toxicity.
These findings secured Breakthrough Therapy Designation from the FDA in August 2025.
For BMS, which paid $800 million upfront and up to $8.4 billion in milestones for global rights outside China, the dataset validated its long-term bet that multi-target ADCs could maintain therapeutic breadth as the PD-1 era plateaus.
Three registrational trials are under way in triple-negative breast cancer, EGFR-mutant NSCLC, and urothelial carcinoma — each testing whether the 55% response rate observed in Phase 1 can translate into survival benefit.
3. Platform Competition and Corporate Renewal
Merck’s ADC Gambit – Turning Data into Strategy
For Merck & Co., ESMO 2025 crystallized a dual narrative: the enduring strength of Keytruda, and the emergence of ADCs as its successor portfolio.
While Keytruda’s combination with Astellas and Pfizer’s Padcev drew ovations for practice-changing bladder-cancer survival curves, investors looked to Merck’s Trop2-targeted ADC sacituzumab tirumotecan (sac-TMT) for evidence of a sustainable post-Keytruda engine.
The clinical evidence was unambiguous. In the OptiTROP-Lung04 Phase 3 trial in China, sac-TMT reduced the risk of death by 40 percent versus chemotherapy in EGFR-mutant NSCLC, doubling median PFS (8.3 months vs 4.3 months).
For comparison, most second-line regimens in this setting yield median survivals near one year; sac-TMT’s hazard ratio implies an extension well beyond that threshold. The magnitude of benefit was maintained across mutation types and even in patients with brain metastases — a subgroup historically resistant to cytotoxics.
In HR-positive/HER2-negative breast cancer (OptiTROP-Breast02), the ADC lowered the risk of progression or death by 65 percent, again doubling PFS from 4.1 to 8.3 months. Given that the control arm received active chemotherapy, these improvements suggest the agent could replace—not merely complement—existing cytotoxics. The safety profile was manageable: grade ≥3 toxicities similar to chemotherapy, and stomatitis, though common, rarely severe.
China’s approval of sac-TMT in October 2025 marked the first regulatory endorsement of a Trop2 ADC developed domestically and globally licensed to a Western major.
Marjorie Green, Merck’s oncology head, interpreted the results not as isolated wins but as validation of a modular ADC platform capable of spanning tumor types. Leerink Partners analysts agreed, labeling the outcome “exemplary” and predicting global uptake if efficacy persists with the slightly lower 4 mg/kg dose chosen for Western trials.
Merck’s second ADC pillar, raludotatug deruxtecan (R-DXd) co-developed with Daiichi Sankyo, extended the company’s reach into gynecologic cancers.
In platinum-resistant ovarian cancer, R-DXd produced a 50.5 percent confirmed ORR across 107 patients, including three complete and 51 partial responses — extraordinary for a population where modern chemotherapy achieves 10–15 percent.
Low-grade ILD in only four cases confirmed that Daiichi’s iterative control of the DXd payload is achieving the safety balance that first-generation ADCs lacked. These quantitative signals explain why the partners swiftly advanced the agent into Phase 3, comparing it directly to investigator’s-choice chemotherapy and exploring Keytruda combinations for earlier lines.
Collectively, sac-TMT and R-DXd turn Merck’s ADC ambitions from abstract diversification into a data-driven portfolio strategy — leveraging statistical superiority to build clinical credibility and investor confidence simultaneously.
Roche’s Partnership Model – Capitalizing on Chinese Innovation
Roche’s ESMO announcements underscored a different calculus: acquiring innovation rather than internalizing it. Its $1.45 billion partnership with Hansoh Pharmaceutical for the CDH17-targeted ADC HS-20110 secured global rights beyond Greater China, extending Roche’s early-stage presence into colorectal cancer. This followed deals with MediLink Therapeutics (c-Met ADC) and Innovent Biologics (DLL3 ADC), alongside a $300 million manufacturing expansion in China.
For Roche, which pioneered Polivy but then lost momentum in solid tumors, these agreements constitute a pragmatic response: invest where proof of concept already exists, and let regional expertise compress development timelines. By integrating mature Chinese ADC programs into its global pipeline, Roche transformed regional clinical data into a competitive advantage.
4. The ADC “Roller Coaster” – Technology 2.0 and Industry Consensus
Observers described ESMO 2025 as the moment ADCs “stole the show.”
Roche’s oncology chief Charles Fuchs compared the field’s evolution to a roller coaster — from euphoria to disillusionment and back — but emphasized that this time the ascent is grounded in data.
Unlike the speculative enthusiasm of a decade ago, today’s optimism is anchored in reproducible efficacy and maturing safety profiles.
GSK’s Hesham Abdullah credited this stability to “second-iteration” engineering: precise antigen selection, refined linkers, and balanced drug-to-antibody ratios. Such control is translating into consistent response rates across tumor types — a milestone that earlier ADCs never achieved.
These refinements also allow dual-targeting constructs and combinations with checkpoint inhibitors, expanding therapeutic geometry beyond monotherapy.
At the symposium, AstraZeneca’s Matt Hellmann stated plainly that ADCs are now capable of displacing chemotherapy in early disease — a prediction supported by Enhertu’s 53 percent relative risk reduction versus Kadcyla.
Not all agree. Moderna’s oncology lead Kyle Holen countered that ADCs remain “just another way to deliver chemotherapy,” arguing that mRNA-based vaccines could reach cancers at stage 1, far earlier than cytotoxic conjugates.
Yet the numbers presented in Berlin suggested that this “different way” of delivering chemotherapy has fundamentally altered its therapeutic index: by concentrating the drug precisely within malignant tissue, ADCs are achieving both higher response rates and longer survival at tolerable toxicity.
5. The Expanding Horizon – Second-Wave Targets and Persistent Challenges
Beyond the marquee results, ESMO 2025 offered a glimpse into the next wave of targets that may sustain the ADC renaissance.
AstraZeneca presented AZD5335, a folate-receptor-α ADC, with a 56 percent objective response rate in platinum-resistant ovarian cancer — performance that rivals early Enhertu benchmarks in HER2-low tumors.
AbbVie’s c-Met-directed ADC telisotuzumab adizutecan (Temab-A) demonstrated meaningful clinical activity across multiple advanced solid tumors at ESMO 2025, with objective response rates of 46 percent in MET-amplified tumors, 26.7 percent in heavily pre-treated colorectal cancer when combined with bevacizumab, and 24 percent in pancreatic ductal adenocarcinoma. These results underscore that even moderate responses across diverse tumor types support continued optimization of linker–payload chemistry within AbbVie’s expanding ADC portfolio.
Together, these findings indicate a broadening ADC ecosystem, where multiple payloads and targets are converging toward the same therapeutic ideal: cytotoxic precision without systemic sacrifice.
Still, key challenges persist. Interstitial lung disease (ILD), though reduced, remains a signature liability of topoisomerase-I ADCs and demands vigilant monitoring. The absence of robust predictive biomarkers limits clinicians’ ability to pre-select patients who will benefit most, potentially blunting the impact of otherwise potent agents.
As such, the next frontier of clinical value will depend less on higher response rates and more on identifying who truly needs these therapies and when. The numbers presented at ESMO demonstrate efficacy; the challenge now is to translate that efficacy into reproducible, safe, and durable benefit across global populations.
6. From Data to Destiny
ESMO 2025 was not merely another oncology conference; it was the inflection point where data coalesced into direction.
Enhertu’s curative-intent trials proved that ADCs can prevent recurrence rather than merely delay it.
Iza-bren’s 55 percent response rate in refractory tumors validated bispecific design as more than theoretical. Merck’s sac-TMT and R-DXd converted statistical superiority into strategic leverage, while Roche’s and Hansoh’s billion-dollar partnership confirmed that innovation geography itself is globalizing.
The numerical signals — hazard ratios halved, response rates doubled, toxicities halved again — collectively reveal an oncology modality entering maturity. If immunotherapy defined the last decade by unleashing the immune system, ESMO 2025 defined the next by mastering cytotoxic precision.
ADCs have crossed the line from pharmacologic experiment to a curative technology — and, for the first time, the data make that claim credible.
Ref.
SystImmune, Inc. and Bristol Myers Squibb Announce First Global Phase I Results of Iza-bren, an EGFR x HER3 Bispecific Antibody-Drug Conjugate, in Patients with Advanced Solid Tumors at ESMO 2025. SystImmune Press Release. 17. 10. 2025.
Waldron, J. ESMO: BMS looks to 'stay ahead of the competition' with ADC's 55% response rate in early-stage trial. Fierce Biotech. 17. 10. 2025.
New Generation of Antibody-Drug Conjugates (ADCs) Shows Unprecedented Promise in Early-Stage Disease. ESMO. 18. 10. 2025.
Manalac, T. Roche Inks Another China ADC Pact With $1.5B Hansoh Bet. Biospace. 17. 10. 2025.
Joseph, A. Merck rolls out some showstoppers at a major cancer conference. Its future may depend on them. STAT. 20. 10. 2025.
Waldron, J. ESMO: The ADC 'rollercoaster' rides on with new generation of therapies. Fierce Biotech. 21. 10. 2025.
Taylor, N. P. ESMO: Daiichi, Merck power ovarian cancer ADC toward pivotal test after passing phase 2. Fierce Biotech. 20. 10. 2025.
Liu, A. Merck grows more ambitious about 'workhorse' TROP2 ADC as partner Kelun posts phase 3 wins. Fierce Pharma. 20. 10. 2025.
Sharma, A. Enhertu could move into 'curative' breast cancer setting on the strength of Phase 3 data. Endpoints News. 18. 10. 2025.
AbbVie to Present New Data at ESMO 2025 Reinforcing Leadership in Advancing Targeted Therapies for Solid Tumors. AbbVie Press Release. 13. 10. 2025.
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