The American Society of Clinical Oncology (ASCO) annual meeting sets the scientific direction for oncology drug development each year. From a landmark RAS-targeted therapy in pancreatic cancer to renewed momentum in immuno-oncology, next-generation antibody-drug conjugates (ADCs), and patient-centered trial design, ASCO 2026 offered a look at where cancer research is headed next.
After the conference, Worldwide Clinical Trials brought together a panel of oncology leaders to share their perspectives on the key themes that emerged at the meeting, as well as their implications for future clinical development.
- Andrew Zupnick, PhD, VP, Oncology Drug Development at Worldwide
- Heidi Gillenwater, MD, Sr. VP, Clinical Development, Adcentrx Therapeutics
- Elise Horvath Walsh, MD, VP, Clinical Development, Kumquat Bioscience
- Victor Moreno, MD, PhD, Director, Clinical Research – Early Phase Trials Unit, START Madrid-FJD
Together, the panel explored how these five insights can translate into execution strategies for oncology drug development.
What Was the Defining Breakthrough Coming Out of ASCO 2026?
Targeted therapies were a major theme at this year’s conference, but an RAS-targeted approach to treating pancreatic cancer stole the show.
The RAS molecule is a key driver mutation that was discovered back in 1982, but drugging it has largely eluded researchers for nearly 40 years. It is a uniquely difficult molecule to target because it folds up when mutated. Because any drug that targets RAS needs to be able to get into this deep pocket, it took a long time to figure out how to directly target it, which is why the data coming out of ASCO is so groundbreaking. This new RAS inhibitor nearly doubled survival for patients, with the survival curve showing that at any point, their chance of death is reduced by 60%. For patients and researchers alike, this is an incredibly meaningful development.
Of course, this “grand slam” for pancreatic cancer wouldn’t have happened without the early incremental studies that came before it. Studies that show modest improvements in response rate, survival, or biologic understanding help create the foundation for these monumental advancements. A better understanding of both the molecular biology and the chemistry of the drugs will hopefully lead to more frequent breakthroughs like this.
This RAS inhibitor data has already opened the floodgates around the concept of “drugging the undruggable.” Moving forward, we will likely see more sponsors going after targeted therapies that hit some very fundamental pathways in oncogenesis.
As development progresses in the space, sponsors can expect to see more point mutation inhibitors, agents that block different RAS activation states, and RAS degraders that eliminate mutant proteins rather than simply inhibit them. Combination strategies that pair RAS-directed therapies with cooperating molecular alterations may lead to even better responses. By moving these types of therapies toward earlier lines of treatment, we’re starting to see some major changes to overall quality of life for patients, not just survival. Patient enthusiasm around these new targeted therapies will likely impact the development process as well, with sponsors potentially seeing unprecedented enrollment rates and faster-moving programs.
What’s Next for Immuno-Oncology?
For the last decade, the field has been dominated by PD-1/PD-L1, CTLA-4, and LAG-3 strategies that target the surface receptors of T cells. This year’s conference highlighted several novel mechanisms of action (MOA), including an ERAP1 inhibitor which alters the repertoire of peptides that are presented into MHC class I. This approach increases the likelihood that T lymphocytes will detect cancer cells. Although early, response rate data for patients across different tumor types was encouraging.
Another novel MOA presented at ASCO 2026 was in vivo CAR-T, which has the potential to transform how therapy is delivered to patients. In one small patient population, there was a 100% overall response rate, many of which were complete responses.
The promise of CAR-T benefits has been touted for years, but to date the manufacturing and logistical complexities have persisted. Patients must go through apheresis, then lymphodepletion, and then the cells must be transported, modified and amplified in the lab. Now, new technology can use a virus to do all of this within the cells themselves. The burdensome manufacturing steps of ex vivo CAR-T therapy are no longer needed, making the process similar to a one-time gene therapy.
This shift will be interesting to watch as we’re already seeing a lot of investment toward in vivo CAR-T focused technologies. For sponsors, an immuno-oncology approach combined with a targeted therapy may be the future of oncology development.
Why are ADCs Moving Toward First-Line Therapy?
ADCs remain one of the most active and strategically important areas of oncology development. What we’re seeing now is the next generation of ADCs which are focused on optimizing variables: multiple / bispecific targets, novel payloads, novel antigens, different linker technologies, and more precise efforts to widen the therapeutic window to find the largest benefit for patients.
One of the key takeaways from ASCO 2026 is the need to move ADCs closer to first-line therapy where they may be able to significantly change survival curves and quality of life. One example shared at this year’s conference was sacituzumab govitecan plus pembrolizumab used in first-line breast cancer. Data showed a significant increase in progression-free survival compared to chemotherapy plus pembrolizumab, suggesting that ADCs may perform better when used sooner in the treatment paradigm.
Dual targeting was another important theme that was explored. One abstract shared at ASCO was a Phase I study of a molecule that targets two highly expressed targets on prostate cancer, PSMA and STEAP1. A molecule that targets both may help address resistance mechanisms and/or heterogeneity among patients whose tumors express one target more strongly than another and may be a strategic model for other molecules moving forward.
How Can Sponsors Do More for Patients?
There is a growing need to do more with less in oncology development – less unnecessary treatment, less patient burden, and less operational complexity. For sponsors, dose optimization and treatment de-escalation are two distinct areas where clinical trials are moving toward a more patient-centric approach.
ASCO 2026 highlighted what the industry is already realizing: very complex protocols with huge expansion phases may not be necessary, especially when the necessary information needed can be gathered from the dose escalation portion of a trial. Modern dose-escalation approaches that include backfill cohorts can enroll enough patients to determine dose safety and biologic activity without requiring extensive randomization across multiple dose levels.
As trials progress, the focus starts to shift from optimizing dosing to de-escalation of therapy. It’s important to consider how avoiding treatment that does not improve outcomes for patients can impact their quality of life. In some instances, this may mean avoiding unnecessary surgery, reducing treatment intensity, or shortening therapy duration. For patients, “less” can make a meaningful difference when it preserves outcomes while also reducing toxicity, inconvenience, or long-term functional impact. Several large Phase III trials shared insights around de-escalation at ASCO, and this is the direction the industry must strive for as we move forward.
How Can Sponsors Accelerate Patient Identification?
There is a lot of excitement around the influx of new, innovative oncology therapies. However, patient identification remains a bottleneck, especially when it comes to biomarker testing and enrollment. Because the ability to find eligible patients quickly can determine whether a trial succeeds, next-generation sequencing needs to happen as early as possible for patients with advanced cancer. Unfortunately, not all patients are able to access the sequencing that is critical for these targeted therapies.
The biggest roadblocks for many oncology trials are the required biomarkers that are not routinely tested for. ADCs, for instance, typically require immunohistochemistry to confirm target expression. Other targeted therapies require unique assays or next-generation sequencing to identify specific mutations. Both scenarios may require new biopsies, with a typical turnaround time of one week minimum. That’s without the added logistics of tissue transfer, which can take another two to three weeks. Patients with end-stage cancer can’t wait that long, and waiting several weeks to confirm eligibility may mean losing the opportunity to enroll a patient at all.
To streamline this critical process and efficiently identify the right patients for the right treatments before it’s too late, sponsors will need to be creative and pragmatic. By partnering early with the labs that are running their biomarkers or other relevant tests, sponsors may be able to reduce friction and speed up the process and ultimately get patients into trials sooner. Sponsors can also accept high-quality local testing and run a retrospective bridging study to complete the central testing later. This allows patients to complete the required testing in a setting that is convenient to them and enroll faster while still preserving data integrity.
Where Oncology Development Goes Next
Oncology development is more precise, biologically sophisticated, and operationally demanding than ever before. ASCO 2026 highlighted the scientific advancements that are changing the landscape of cancer research and patient outcomes for the better, as well as the areas where we may continue to see growth over the coming year.
What can we hope to see at ASCO 2027? Our panelists projected that cell therapy in solid tumors is an area still ripe for innovation, following on the early ex vivo CAR-T results seen this year. RAS and other ‘undruggable’ target development will likely continue to accelerate, with new inhibitors, degraders, combinations, and resistance strategies moving through the pipeline. Artificial intelligence may also play a role in identifying the most appropriate molecules for future drugs, accelerating discovery, and speeding development decisions.
Breakthroughs in targeted therapies, immuno-oncology, ADCs, dose optimization and de-escalation, and patient identification are creating new opportunities for sponsors and the patients we aim to help. As oncology clinical development continues to advance, innovation and intention must be at the heart of trial development and execution.
Ready to translate these insights into a robust oncology program? Reach out to our team to discuss how we can help you move forward, and watch the full webinar here.
