The development of antibody-drug conjugates (ADCs) requires a seamless transition from preclinical discovery to clinical execution. While regulatory and operational considerations play a crucial role, the true driver of clinical success is the science itself. Effective ADC clinical trials should be shaped by robust preclinical data, ensuring that every decision— from dose selection to patient stratification—is grounded in scientific rationale.
Building a Clinical Strategy from Preclinical Insights
Preclinical studies provide a wealth of information that, when leveraged correctly, can optimize clinical trial outcomes. Key areas where preclinical insights must inform clinical strategy include:
- Target Validation and Biomarker Selection: Understanding antigen expression patterns, tumor heterogeneity, and potential off-target effects in preclinical models helps define eligibility criteria and patient segmentation in clinical trials. Companion diagnostic assays should be developed early to ensure that the right patients are enrolled in the study.
- Pharmacokinetics and Dose Selection: The relationship between drug exposure, efficacy, and toxicity must be carefully modeled. Preclinical pharmacokinetic (PK) and pharmacodynamic (PD) data should guide initial dosing strategies, including dose escalation schemes and therapeutic index optimization.
- Mechanisms of Resistance and Combination Strategies: Preclinical resistance models can provide early indications of escape mechanisms, informing the design of combination therapies or sequential treatment strategies that may improve clinical response rates.
Ensuring a Seamless Preclinical-to-Clinical Transition: Adapting to Emerging Data
Preclinical insights should continue to guide clinical decisions even after a trial has begun. While clinical trials are carefully designed based on extensive preclinical data, unexpected findings can arise. Having the ability to conduct additional preclinical studies mid-trial can offer critical insights to refine clinical strategies. This flexibility allows for science-driven pivots, ensuring that adjustments are based on data rather than assumptions. Some scenarios where additional preclinical investigations may support clinical decision-making include:
- Unexpected Toxicity Profiles: If clinical patients exhibit toxicities not predicted in animal models, additional preclinical studies can help refine dosing strategies or identify biomarkers for patient exclusion.
- Variable Patient Responses: If subsets of patients are responding significantly better than others, preclinical modeling can explore new biomarkers that could refine inclusion criteria for subsequent trial phases.
- Mechanism of Action Refinement: Mid-trial in vitro or in vivo studies can provide deeper insights into tumor microenvironment interactions, allowing trial designs to pivot based on new biological understanding.
Balancing Scientific Rigor with Clinical Execution
To successfully integrate preclinical learnings into clinical strategy, ADC development teams must establish a feedback loop between preclinical and clinical teams. This includes:
- Early Cross-Disciplinary Collaboration: Bringing together translational scientists, clinicians, and regulatory experts ensures that preclinical findings translate seamlessly into trial protocols.
- Adaptive Clinical Trial Design: Implementing adaptive trial methodologies allows for data-driven modifications that refine patient selection, dosing, and endpoints based on emerging scientific insights.
- Regulatory Alignment: Ensuring that ongoing preclinical studies align with regulatory expectations can prevent delays while allowing science-driven modifications to the clinical strategy.
A Science-Driven Path to ADC Success
The most successful ADC trials are those where scientific insights—not rigid protocols—drive decision-making. By continuously integrating preclinical and clinical data, development teams can optimize patient outcomes, mitigate risks, and ultimately accelerate the path to regulatory approval.
For organizations developing ADCs, a flexible, science-first approach ensures that each stage of clinical progression remains informed by the latest biological insights. By prioritizing preclinical-to-clinical alignment, teams can increase trial success rates and bring transformative therapies to patients faster.
Partnering for ADC Development Success
At TD2 Oncology, we offer a full suite of preclinical and clinical services to advance ADC therapies from the lab to the clinic. Our expertise in translational research, adaptive trial design, and regulatory strategy ensures that ADC programs remain scientifically driven and positioned for success.
Learn more about our tailored services specifically for ADC clinical trials.