As clinical research evolves, disruptive trial designs are reshaping how oncology advances. By integrating novel methodologies, strategic innovation, and patient-centered approaches, MEDSIR is driving a new era in cancer research, one that accelerates development, enhances efficiency, and delivers more meaningful therapeutic progress for patients worldwide.
In recent years, clinical trials have undergone a significant transformation, driven by the need to accelerate the access to safer and more effective therapies. Despite scientific progress, traditional clinical research methods still face persistent challenges, including long recruitment timelines, low participation retention, high operational costs, and limited representation of diverse populations1. These barriers highlight the urgent need to rethink how clinical trials are designed and conducted.
In 2023, Nature Review Drug Discovery published an article on a workshop co-sponsored by the Food Drug Agency (FDA) and the Drug Information Association (DIA), which focused on advancing complex innovative trial design to efficiently deliver medicines to patients1. Interestingly, the article noted that oncology is one of the leading therapeutic areas driving innovation, with many proposals being submitted through scientific advice working parties to foster early regulatory scientific engagement.
MEDSIR, a company founded in 2012 by scientific experts, has pioneered a new model of managing strategic oncology trials, offering end-to-end support from study design to publication. This previous article showcases how MEDSIR transforms oncologist’s innovative ideas into high-quality clinical trials that redefine drug development strategies.
More than a decade later, MEDSIR is growing and innovating with the development of disruptive clinical trials that integrate novel approaches to advance innovation. Recent examples such as the CADILLAC, DEMETHER, and THERANOVA studies illustrate MEDSIR’s commitment to advancing patient-centered and scientifically robust trial designs.
DEMETHER: optimizing the sequence to improve patient’s survival
Breast cancer is the most diagnosed cancer in women and about 15 to 20% of cases are HER2-positive (HER2+), meaning they overexpress HER2 protein. These cancers tend to grow faster and spread aggressively to other organs. Currently, the first treatment option for patients with metastatic HER2+ breast cancer combines chemotherapy with two HER2-targeted monoclonal antibodies (pertuzumab and trastuzumab), followed by maintenance therapy with these antibodies. If this regime fails, the next treatment option is trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate.
The DEMETHER trial (NCT06172127), funded by Roche, is an international, multicenter, open-label study that will evaluate the efficacy and safety of the new treatment strategy involving T-DXd, but this time as an initial therapy, followed by maintenance with a fixed-dose combination of pertuzumab and trastuzumab (known as PHESGO) in patients with HER2+ advanced breast cancer. Enrollment began in mid-2024 across Europe, the United States, and Brazil and its main goal is to find the right balance between the potent antitumor activity of T-DXd with the long-term tolerability of PHESGO maintenance, potentially offering an effective and better tolerated first-line option for these patients.
With this study, MEDSIR’s innovative design is focused on patient benefit, aiming to optimize first-line therapy by combining the current standard of care, established after the positive results of the CLEOPATRA11 study- with a short induction phase of T-DXd. Findings from DESTINY-Breast0912, presented in ASCO 2025, demonstrated that T-DXd plus pertuzumab significantly improved progression-free survival over the standard regime. By leveraging these results, DEMETHER seeks to redefine first-line therapy in HER2+ breast cancer while integrating approved and novel agents in a way that preserves efficacy, minimizes cumulative toxicity and enhances patient convenience and quality of life.
CADILLAC: external control arms transforming trial’s quality and efficacy
Worldwide, 70% of breast cancers are positive for hormone receptors (HR)2 and despite the existence of numerous therapeutic agents, survival rates in patients with advanced HR-positive/HER2-negative have been historically poor and only improved recently. This improvement can be attributed to the standard of care in the first line, constituted of endocrine therapy (to reduce estrogen levels) and CDK4/6 inhibitors (to stop the division and growth of cancer cells), which have demonstrated positive clinical results in previous studies –– such as ribociclib in MONALEESA-2, -3 and -7 trials3-5, palbociclib in the PALOMA-1, -2 and -3 trials6-8, or abemaciclib in MONARCH-2 and -3 trials9,10–– . However, most of these patients who respond develop resistance and progress eventually. For this reason, advances remain to be made toward defining the optimal treatment.
The CADILLAC study aims to evaluate in patients with this type of breast cancer the efficacy and safety of the combination of two drugs: Camizestrant (a novel selective estrogen receptor degrader) together with the CDK4/6 inhibitor Ribociclib. However, the trial will not be developed in a conventional fashion. Two groups of patients will be included: one will consist of 150 participants who will receive the experimental treatment, and the other one will be an external group that will include data from an existing database of patients who had previously received the standard of care, which is endocrine therapy (either aromatase inhibitor or fulvestrant) plus ribociclib, as a control arm. This study will be funded by AstraZeneca, who will also provide camizestrant, and Novartis, who will provide ribociclib.
The interest of MEDSIR in using an external control arm in the CADILLAC study is to reduce the number of patients who will need to be enrolled and who may be treated with less effective therapies, allowing to focus on evaluating the study treatment, rather than recruiting and monitoring a control group. Furthermore, external control groups posse advantages in operational challenges, allowing to speed up the trial process and optimize the cost-efficiency.
THERANOVA: a “magic bullet” for cancer research
The THERANOVA study differs from all previous trials conducted by MEDSIR to date. It focuses on theranostics, a precision medicine approach that integrates diagnosis and therapy through radiopharmaceuticals - radioisotopes conjugated to a ligand targeting cancer cells. The approach involves two radiopharmaceuticals: the first binds to an overexpressed target in cancer cells to enable SPECT/PET imaging (diagnosis), while the second binds to the same target and delivers localized radiation that induces DNA damage (therapy). Clinical success of trials like NETTER-114, 215, and THERA-P16 in neuroendocrine and prostate cancer respectively, has positioned theranostics as a rapidly expanding field with promising potential in oncology.
Funded by Novartis, the THERANOVA study will establish a platform to evaluate the efficacy of several radiopharmaceuticals in different tumor types. An initial diagnostic phase will be developed, where target expression of a potential molecule will be evaluated in a small group of patients. Once the diagnostic phase confirms that the molecule is a suitable target for the radiopharmaceutical to be bound, the therapeutic phase will begin, this time not only tagging the cancer cells, but also treating them. Due to the innovative nature of radiopharmaceuticals, at the conclusion of each phase, a multidisciplinary committee will assess the safety and efficacy results carefully.
THERANOVA’s excellence resides in incorporating an innovative agent that has recently shown promising results while constructing a platform with valuable data of a novel technique that is redefining cancer care. At the same time, it preserves a patient-centered strategy with an expert committee evaluating each step to enhance patient’s outcome and ensure scientific excellence.
Conclusion
New technologies are reshaping all industries, including healthcare and drug development. The impact on clinical trials is still emerging, with innovative approaches aiming to transform how new therapies are researched and delivered to patients. MEDSIR’s forward-thinking strategy embraces this transformation as shown in CADILLAC, DEMETHER and THERANOVA, where results are anticipated to be highly promising and impactful. Besides, these complex and innovative trials reflect the company’s commitment to improving patient’s lives and brings strategic value to promising drugs in development.
References
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