Precision in Practice: How to Operationalize the Promise of ADCs in Oncology Pipelines
Our expert explores how advances in antibody-drug conjugate (ADC) linker-payload technology is shaping more efficient, clinically grounded oncology development strategies.
Antibody-drug conjugates (ADCs) are transforming some of the most promising modalities in oncology pipelines, thanks to advances in bioconjugation chemistry, linker-payload technologies and a growing track record of clinical success. But for teams overseeing oncology development, the real question is: how do you accelerate the path to market for these complex agents while mitigating their unique operational risks?
Looking to accelerate ADC development within your oncology pipeline? Contact our experts.
With more than a decade of experience in ADC studies, our experts Wouter Bartholomeus, MD, Executive Medical Director and Kin Woo, MD, Senior Medical Director at Syneos Health, offer an insider’s view into what’s driving success—and what still challenges sponsors—in this high-stakes therapeutic category.
From Breakthrough Science to Smart Strategy
The early struggles of ADCs are well-documented: antigen selection, off-target toxicity, linker instability and inefficient payload delivery limited their clinical viability. But the science has evolved. Innovations in payload selection and linker technologies are producing ADCs with better pharmacokinetics and more targeted activity, making them suitable for use across tumor types, including hematological indications and solid tumors such as HER2-positive breast, non-small cell lung and gastric cancers.
That scientific leap, however, doesn’t eliminate the strategic hurdles. As sponsors pursue approvals for single ADCs across multiple tumor types, a portfolio-level view of development becomes essential. “What we’re seeing is that success increasingly hinges on the ability of sponsors to effectively manage toxicity profiles, coordinate across multiple studies and collaborate with experienced partners who can navigate this complexity on a global scale,” notes Dr. Woo.
The New Standard in Clinical Trial Design
Successful ADC trials demand more than traditional study design—they require upfront planning that reflects the agent’s mechanism of action, toxicity and tumor biology. That includes:
- Indication sequencing based on differential expression of targets (e.g., HER2, TROP2, Nectin-4)
- Integrated biomarker strategies that link early phase exploratory endpoints with registrational trial planning
- Flexible protocol design that enables seamless transition from phase I dose-escalation to expansion cohorts
- Proactive adjudication pathways for known toxicities like interstitial lung disease (ILD), neuropathy or ocular adverse events (AEs)
“You can’t afford to treat each study as a standalone effort,” Dr. Bartholomeus explains. “The goal is to synergize during every step of development—so you’re not just reacting to data but accelerating based on it.”
Managing ADC-Specific Toxicities: A Critical Differentiator
As with traditional chemotherapy or immuno-oncology agents, ADCs—depending on their payload—carry a unique spectrum of off-target effects. Ocular, pulmonary and dermatologic toxicities are among the most concerning and can derail development if not anticipated and managed proactively.
In ADC trials, it’s increasingly common to use independent adjudication committees to evaluate events like ILD/pneumonitis or ocular toxicity. This added layer of oversight helps ensure adverse events are consistently assessed and appropriately categorized. “Clarity on relatedness is critical in ADC trials,” says Dr. Bartholomeus. “That includes revisiting cases where the drug relationship may not be immediately clear—working closely with sites to confirm AE details. That’s essential for safeguarding both patient well-being and data integrity—especially when delivering potent payloads like DNA-damaging agents, topoisomerase inhibitors or microtubule-targeting cytotoxics.”
Building a Cohesive Global Program—Design Meets Execution
Today’s leading ADC sponsors are executing coordinated global programs that optimize data capture, reduce duplicative effort and streamline execution. While each protocol may be distinct, aligning studies under a unified operational umbrella enables:
- Cross-study safety signal detection
- Faster start-up timelines through centralized governance
- Real-time application of insights across tumor types
“When the same team oversees multiple studies of a compound across indications, it becomes easier to harmonize patient management and apply insights in real time,” says Dr. Woo. “That cohesion becomes a competitive advantage.”
Why Sites—and Patients—Are All In on ADCs
One underappreciated edge in ADC development? High investigator and patient engagement. “We’ve seen that when sites are confident in the clinical potential of an ADC—especially when they’ve seen real responses in earlier trials—they become strong recruitment allies,” according to Dr. Woo.
This enthusiasm translates to faster enrollment and greater compliance, even in highly competitive indications. But it doesn’t happen automatically. It takes strong site relationships, efficient startup models and deep experience in selecting the right geographies at the right time.
What’s Next?
As the oncology landscape shifts from broad-spectrum cytotoxics to precision-guided therapies, ADCs are poised to become a mainstay in cancer care. Beyond promising data, success requires operational fluency in navigating toxicity, trial design and global portfolio execution. For clinical development leaders, partnering with teams that know how to translate scientific promise into strategic execution will be the difference between playing catch-up and leading the next frontier in oncology innovation.
How are you preparing your oncology portfolio for the future of ADCs? Contact our experts.
Contributors
Wouter Bartholomeus, MD | Executive Medical Director
Kin Woo, MD | Senior Medical Director
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