In the ever-evolving field of cancer treatment, a powerful novel approach is changing the landscape: antibody-drug conjugates (ADCs). These cutting-edge therapies offer renewed hope for patients and groundbreaking opportunities for pharmaceutical and biotech companies. In this blog, we will explore the essence of ADCs, successes, challenges, and their promising future.
Imagine a therapy that can precisely target and eliminate cancer cells while sparing healthy tissue – this is the promise of ADCs. These innovative treatments combine the targeting ability of monoclonal antibodies with the potent, cell-killing power of cytotoxic drugs by maximizing efficacy while minimizing side effects.
Understanding how ADCs work involves delving into their three components:
ADCs are not just theoretical – they influence patients' lives. Here are some of the latest and most impactful examples:
Approved for advanced urothelial cancer, Padcev® targets Nectin-4, a protein highly expressed in bladder cancer. In a pivotal phase II clinical trial, Padcev® demonstrated an overall response rate (ORR) of 44%, with 12% of patients achieving a complete response (CR) and with a median duration of response (DOR) of 7.6 months, providing significant benefits for patients who progressed on other therapies (Chang, et al., 2011).
For HER-2-positive breast cancer, Enhertu® offers a new lifeline. In the DESTINY-Breast01 trial, Enhertu® achieved an ORR of 60.9%. The median duration of response was 14.8 months, and the median progression free survival (PFS) was 16.4 months. These impressive results have made Enhertu® a crucial option for patients with previously treated metastatic disease (Modi, et al., 2020).
Used for Hairy Cell Leukemia, Lumoxiti® targets CD22 and has provided substantial clinical benefits. In clinical trials, Lumoxiti® achieved an ORR of 75%, with 30% of patients experiencing a durable CR lasting at least six months. These outcomes highlight Lumoxiti’s® effectiveness in treating this rare blood cancer (Kreitman, et al., 2018).
Approved for triple-negative breast cancer, Trodelvy® targets Trop-2 and has shown remarkable improvements in progression-free survival. In the ASCENT trial, Trodelvy® demonstrated an objective response of 35%, with a median PFS of 5.6 months compared to 1.7 months for chemotherapy. The median OS was also significantly improved at 12.1 months versus 6.7 months for chemotherapy (Bardia, et al., 2021).
Polivy® is combined with Bendamustine and Rituximab for relapsed or refractory diffuse large B-cell lymphoma. Polivy® targets CD79b and has demonstrated significant clinical benefit. In the GO29365 trial, the addition of Polivy® to Bendamustine and Rituximab resulted in a complete response rate of 40% compared to 18% without Polivy®, underscoring its effectiveness (Sehn, et al., 2020).
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Some Key Oncology Acronyms |
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Acronym |
Meaning |
Explanation |
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OS |
Overall Survival |
The duration from randomization to death. The “gold-standard” primary endpoint. |
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PFS |
Progression-Free Survival |
The duration from randomization to the first sign of disease progression or death. |
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ORR |
Overall Response Rate |
The proportion of patients in a study whose cancer shrinks or disappears after treatment. |
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CR |
Complete Response |
The absence of any detectable signs of a tumor. |
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DOR |
Duration of Response |
The period during which a tumor remains responsive to treatment without increasing in size or spreading. |
The market for ADCs is expanding rapidly, driven by their proven efficacy and continuous innovation in biotechnology. Currently, several ADCs have received approval, with many more in various stages of clinical development. Key players in the market include both established pharmaceutical giants and innovative biotech firms. Recent market entries have demonstrated significant commercial potential, with ADCs like Trastuzumab Deruxtecan (Enhertu®) achieving substantial market penetration and strong sales.
Future growth projections for the ADC market are robust. The increasing incidence of cancer, combined with the growing demand for targeted therapies, suggests that the ADC market will continue to expand. Additionally, advances in ADC technology, such as improved linker stability and novel cytotoxic agents, are expected to enhance the therapeutic window of these drugs, making them more attractive to investors and clinicians.
Despite their promise, ADCs face several hurdles:
ADC development is a collaborative effort involving academic institutions, biotech firms, pharmaceutical companies, and contract research organizations (CROs). These partnerships are crucial for advancing ADC technology and bringing new therapies to market. Academic researchers often provide the foundational science and early-stage discoveries that drive ADC innovation. Biotech firms typically focus on translating these discoveries into viable therapeutic candidates. At the same time, pharmaceutical companies bring the necessary resources and expertise to conduct large-scale clinical trials and navigate the regulatory landscape.
CROs play a vital role in this ecosystem by providing specialized services that support the development and commercialization of ADCs. These services include clinical trial management, regulatory consulting, data management, and more by leveraging the expertise of CROs, biotech and pharmaceutical companies can streamline their development processes, reduce cost, and accelerate the time-to-market for their ADC products.
Moreover, incorporating the patient’s voice into ADC development is crucial to understanding the full impact of these therapies.
Global regulatory agencies, including the FDA and EMA, emphasize integrating patient perspectives in drug development through frameworks that ensure treatments align with patient needs and experiences(FDA, 2022) Electronic Patient-Reported Outcomes (ePROs), such as the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy (FACT-G), play a vital role in capturing patient’s perspectives on their quality of life, beyond the clinical outcome measured by clinical outcomes by healthcare providers.
By utilizing ePROs, researchers can gain insights into the side effects, physical and emotional well-being, and overall treatment experience from the patient’s point of view, ensuring that the development of ADCs is aligned with improving not only survival but also the quality of life of cancer patients. Signant Health has a broad experience in Health-related Quality of Life (HRQoL) patient-reported measures and offers advice on best practices to optimize their implementation in clinical studies.
ADCs represent a major advancement in cancer therapy, offering new hope for patients. Signant Health was key in 40% of FDA oncology drug approvals and 38% of EMA approvals in 2023. Explore the transformative potential of ADCs with us—contact us to learn how we can support your oncology studies.
Bardia, A., Hurvitz, S., Tolaney, S., Loirat, D., Punie, K., Oliveira, M., . . . Carey. (2021). ASCENT Clinical Trial Investigators. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med, 384(16):1529-1541. doi:10.1056/NEJMoa2028485.