The American Society of Clinical Oncology annual meeting in June brought together more than 40,000 oncology professionals for opportunities to connect with and learn from experts focused on transforming the landscape of cancer care for patients worldwide. There was no shortage of insightful discussions, especially about what may be considered practice-shifting advances in the continuous examination of groundbreaking treatments. Some scientific findings announced at ASCO quickly became headline news creating excitement among oncology experts, patients and caregivers alike. These key findings emphasized the hope innovative therapies and approaches can bring to patients in terms of improving disease-progression-free survival rates while also accounting for unique quality of life needs and much more.

However, with more than 5,000 abstracts presented at this year’s meeting, ASCO provided the ideal backdrop to initiate much-needed dialogue between researchers, clinical trial sponsors, service partners and patients about a wide spectrum of expanding possibilities in patient-centered cancer care and research. Below, we review several noteworthy areas of discussion coming out of ASCO 2024 and how they may tangibly impact care paradigm pathways for more patients as we look ahead. 

Gaining momentum: radioligand therapeutics  

How novel oncology therapies may replace traditional chemotherapy-based treatment plans was a running point of discussion at ASCO this year. In some cases, the novelty of an approach may be repurposing a treatment used for many therapeutic areas for decades. Together with several other isotopes, such as Lutetium-177 and Actinium-225,radiopharmaceuticals are being used to develop novel radioligand therapeutics. This is gaining attention from cancer care stakeholders due to their targeted modality, which delivers radioactive agents directly to cancer cells or the tumor microenvironment. To date, clinical benefits of RLTs are showing promise for the treatment of neuroendocrine tumors and advanced prostate cancer, and they are being studied across various other tumor types. 

At ASCO, findings from a Phase I dose-escalation study examining Johnson & Johnson’s ²²⁵Ac-conjugated anti-hexokinase 2 antibody-based targeted RLT JNJ-6420 for the treatment of metastatic castration-resistant prostate cancer were announced. The first RLT to target the hK2 enzyme, the study showed the treatment “elicited profound and durable biochemical and radiographic responses.” Data showed among 57 patients receiving ≥150 μCi, there was a 45.6% PSA50 response rate, a biomarker measure of prostate-specific antigen that is associated with prolonged survival. It is also important to note that 61% of these patients experienced a Grade 3 or higher treatment-emergent adverse event, resulting in four treatment-related deaths. Study investigators are currently reviewing dosing adaptations, including dose cap and scheduling, to better address adverse events. 

Given the overall response rates associated with RLTs, Johnson & Johnson and a growing number of pharmaceutical companies are dedicating resources to further evaluation, indicating that interest in exploring the fuller potential of RLTs is not slowing down. In the past few months alone, there have been several billion to multi-billion dollar development partnerships among pharmaceutical companies, including:

• AstraZeneca finalizing a $2 billion buyout with Fusion Pharmaceuticals in March to develop its oncology pipeline, including its prostate-specific membrane antigen-directed radioconjugate FPI-2265, which is currently in Phase II development for the treatment of metastatic castration-resistant prostate cancer.
• Weeks before ASCO, Eli Lilly added to its late 2023 $1.4 billion acquisition of Point Biopharma for its radiopharmaceutical assets by entering into a collaborative partnership with Aktis Oncology, for up to $1.1 billion, to pursue its radiopharmaceutical pipeline, which consists of seven programs for treatment of various solid tumors.
• In December 2023, Bristol Meyers Squibb acquired RayzeBio for $4.1 billion to develop its pipelines of next-generation RLTs for solid tumors, including small cell lung cancer, hepatocellular carcinoma and neuroendocrine tumors. 

These partnerships emphasize the industry’s focus on the potential applications of RLTs’ transformative modality to offer patients new options to traditional treatment plans. Moving forward, it will be critical for trial sponsors to consider the intricacies of optimizing RLT development. This includes considerations around:

• Selecting sites with appropriate diagnostic and imaging equipment to better identify patients suitable for treatment with RLTs. Also, sites will need to be adequately staffed with expert nuclear medicine physicians and staff trained in calibration and dosimetry collection for effective RLT administration.
• Carefully monitoring and evaluating varying country and regional regulations for RLT development, especially since this class of therapies is not comprehensively addressed in many established cancer policies. 

Potential of personalized mRNA cancer vaccines 

The oncology R&D community has worked to fine-tune clinical research and related evaluations of investigational cancer vaccines. These therapies have not always succeeded in clinical testing for various cancers (e.g., brain, lung and kidney). However, in recent years, further evaluation of personalized messenger RNA-based therapeutic vaccine technology platforms is offering patients and providers hope with tailored therapy design and production based on the unique genetic sequencing of the patient’s tumor. For example, Moderna and Merck & Co.’s mRNA-4157 individualized neoantigen vaccine therapy allows researchers to analyze an individual’s genes and cancer tumor to find up to 34 mutations that may help their immune system fight the disease. 

At ASCO 2024, encouraging findings from the KEYNOTE-942 Phase IIb study examining mRNA-4157 in combination with Merck & Co.’s Keytruda® (pembrolizumab) for the treatment of high-risk melanoma (stage III/IV) were presented during a rapid oral abstract session. From three-year follow-up results, mRNA-4157 in combination with Keytruda showed to reduce the risk of disease recurrence or death by 49%. The investigational vaccine was also found to reduce the risk of distant metastasis or death by 62% compared to Keytruda alone. Additionally, the 2.5-year recurrence-free survival rate of mRNA-4157 in combination with Keytruda was 74.8% compared to Keytruda alone (55.6%). 

These benefits were observed across exploratory patient subgroups, which signifies the potential to reach a wider range of patients with resected high-risk melanoma. Moderna and Merck are also evaluating the vaccine’s safety and efficacy in patients with renal cell carcinoma, urothelial carcinoma and cutaneous squamous cell carcinoma and recently initiated a Phase III trial to examine the treatment combination in patients with high-risk melanoma and non-small cell lung cancer. Beyond these companies’ efforts, Genentech and BioNTech are also partnering to evaluate the latter’s mRNA-based individualized neoantigen-specific immunotherapy candidate autogene cevumeran for the treatment of resected pancreatic ductal adenocarcinoma, a difficult-to-treat cancer. Published in Nature in May, three-year follow-up data from a Phase I trial evaluating the vaccine for this cancer type showed eight of 16 patients elicited an immune response for up to three years after treatment administration. Additionally, the personalized vaccine is in early stages of evaluation for treatment of colorectal cancer, melanoma and metastatic cancers. 

As we look ahead, it will be interesting to monitor additional findings from late-stage studies that examine how viable cancer vaccines may be for varying cancers. 

Democratizing R&D across countries 

Important advances in potentially game-changing cancer therapies are rightfully exciting to providers and patients in need of more options. However, it is equally important to match treatment innovation with dedicated efforts to broaden access to care and related clinical trials across patient populations, regardless of location. 

To develop a deeper perspective about addressing disparities in cancer care and improving health outcomes for all, there was discussion at ASCO about the value in greater country and site diversification for clinical trial programs. According to a 2024 global oncology trends report, cancer incidence is expected to rise significantly through 2050, particularly in lower-income countries. Disparities between cancer-related survival rates and health outcomes can widen depending on multiple variables. For one, lower-income countries may lack cancer registry data to sufficiently quantify disparities in cancer-related survival rates. Also, countries with lower gross domestic product and fewer resources can have substantially lower five-year cancer survival rates compared to higher GDP countries (e.g., Bulgaria at approximately $32,000 GDP per capita and 39% five-year survival rate compared to United States at $80,000 GDP per capita and 65% survival rate). 

Experts at ASCO noted that with clinical trial sponsors considering trial settings in lower-income countries, such as South Africa and Brazil, there is an opportunity to gain local-level insights and experience to then help shift standard of care for patients in the area. 

Trial sponsors, clinical research organization partners and other industry stakeholders are using artificial intelligence-driven solutions to extract critical insights from real-world data to better understand how to expand research settings in these regions with the appropriate infrastructure to also ensure quality data outcomes are captured and cancer-specific health outcomes can improve. For example, as cancers vary in severity and speed of progression, earlier detection is a key approach to better survival for tumors with lower survival rates and less variation across countries. Lower-income countries may focus on increasing screenings or finding ways to improve access to advanced biomarker and imaging testing for patients. For tumors with more cross-country variation, it may be beneficial for countries to benchmark their outcomes and work alongside peer countries for real-time comparisons and to enable quicker adjustments to care strategies and clinical trial protocols, if being conducted locally. 

Expanding upon pathways with promise 

This year’s ASCO meeting theme was “The Art and Science of Cancer Care: From Comfort to Cure.” The global oncology community brought this theme to life, coming together to explore the potential that transformative science must meet for varying patient needs across the globe. Gathering at ASCO helps reinforce a community-wide commitment to driving actionable change for patients. 

Though we know we have a long way to go to better support all patients with cancer, we also know the promise for better outcomes is there. It is exciting to see what is coming down the pike in practice-changing cancer care and related R&D progress as collective efforts to provide breakthrough therapies and approaches grow. 

 

Michael Armstrong, MD, PhD, Senior Director, Medical, Hematology-Oncology Center of Excellence, IQVIA 

 

Scott Bazemore, Senior Director, Oncology Therapeutic Strategy Lead, Therapeutic Science and Strategy, IQVIA 

 

Gijsbert Veerman, Vice President, Therapeutic Area Head – Oncology, IQVIA