Oncology On The Go

In a recent interview with CancerNetwork®, Nicholas Hornstein, MD, PhD, an assistant professor at the Donald and Barbara Zucker School of Medicine of Hofstra University and Northwell Health, discussed emerging data and clinical shifts in the care of patients with gastrointestinal (GI) cancers ahead of the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.
Advancements in Colorectal Cancer

Hornstein highlighted the increasing integration of targeted therapies into the first-line setting for patients with colorectal cancer (CRC). For those with BRAF V600E-mutated metastatic disease, data from the phase 3 BREAKWATER trial (NCT04607421) support moving targeted therapy into the first line.1 He noted that initiating these therapies early is critical, as a significant percentage of patients may experience rapid clinical decline and lose the opportunity for second-line treatment if targeted options are delayed.
In the HER2-positive space, clinicians currently utilize tucatinib (Tukysa)-based regimens or fam-trastuzumab deruxtecan-nxki (Enhertu). Hornstein also anticipated the arrival of bispecific antibodies, such as zanidatamab-hrii (Ziihera), which are expected to gain approval in upper GI cancers before moving into the CRC landscape.
The Role of ctDNA and Pancreatic Cancer

Regarding localized disease, Hornstein discussed the potential for circulating tumor DNA (ctDNA) to guide adjuvant therapy for patients with stage II colon cancer. Data from trials like CIRCULATE (NCT05174169) are expected to further clarify how ctDNA can assist in the escalation or de-escalation of treatment.2 In pancreatic cancer, the phase 3 RASolute 302 trial (NCT06625320) investigating daraxonrasib is poised to change the standard of care for patients with second-line pancreatic cancer immediately upon an anticipated regulatory approval.3
Barriers to Precision Medicine

A primary unmet need that Hornstein identified was the low rate of biomarker testing; currently, only about half of patients with metastatic disease receive necessary sequencing or microsatellite instability testing. Hornstein emphasized that multidisciplinary cooperation and improved systems are essential to ensure all patients with targetable mutations receive appropriate care. Finally, he highlighted the development of large language model tools to assist clinicians with data ingestion and clinical trial matching.
References

1.        Kopetz S, Wasan HS, Yoshino T, et al. BREAKWATER: primary analysis of first-line (1L) encorafenib + cetuximab (EC) + FOLFIRI in BRAF V600E-mutant metastatic colorectal cancer (mCRC). J Clin Oncol. 2026;44(suppl 2):13. doi:10.1200/JCO.2026.44.2_suppl.13
2.        Dasari A, Yu G, Kopetz S, et al. NRG-GI008: colon adjuvant chemotherapy based on evaluation of residual disease (CIRCULATE-NORTH AMERICA). J Clin Oncol. 2026;44(suppl 16):TPS3686. doi:10.1200/JCO.2026.44.16_suppl.TPS3686
3.        Wolpin B, Wainberg ZA, Hendifar A, et al. Daraxonrasib, a RAS(ON) multi-selective inhibitor vs chemotherapy in previously treated metastatic pancreatic adenocarcinoma (mPDAC): Primary and final analysis from the phase 3 RASolute 302 study. J Clin Oncol. 2026;44(suppl 17):LBA5. doi:10.1200/JCO.2026.44.17_suppl.LBA5

In a cobranded episode between Oncology on the Go, hosted by CancerNetwork®, and the American Society for Transplantation and Cellular Therapy (ASTCT)’s program ASTCT Talks, Mitchell E. Horwitz, MD, highlighted key developments and ongoing initiatives related to allogeneic and cord blood transplantations among patients with different hematologic malignancies. The conversation touched upon the impact of omidubicel-onlv (Omisirge) on patient outcomes, current research on reducing the risk of graft-versus-host disease (GVHD) among transplantation recipients, and strategies for providing effective prophylaxis during treatment, among other topics. 
According to Horwitz, omidubicel has served as an “important graft source” for pediatric patients while improving cord blood transplantation for adults since its FDA approval in April 2023 for patients 12 years and older with hematologic malignancies. He also spoke to the importance of the FDA’s approval of the agent in December 2025 for patients with severe aplastic anemia and no compatible donors following reduced intensity conditioning. Regarding those with severe aplastic anemia, he noted that omidubicel may considerably improve the feasibility of cord blood as a graft source for transplantation.
Beyond these approvals, Horwitz described ongoing work dedicated to reducing the risk of GVHD following cord blood-derived transplantation, citing a pilot study that he and colleagues are conducting to determine the feasibility of adding a co-stimulatory blocking monoclonal antibody to help further limit this risk. Additionally, he emphasized surveilling for viruses like Epstein-Barr virus, HHV-6, and cytomegalovirus to mitigate the risks of delayed immune recovery following transplantation.
“It’s important to have all these [graft sources], whether it be cord blood, mismatched family members, mismatched unrelated donors, and matched siblings…to be made available [and] studied extensively,” Horwitz concluded. “We need to find what the best niche would be for each of these graft sources and make sure that [they] are utilized at the various institutions. The nuances, such as infection prophylaxis or infection monitoring, [should become] familiar to the transplant centers. By doing that, we can continue this trend of having a graft source for everyone and improving outcomes.”
Horwitz is a professor of Medicine, Hematologic Malignancies and Cellular Therapy at Duke University School of Medicine and cellular therapy and stem cell specialist at Duke Cancer Institute.
References

FDA approves cell therapy for patients with blood cancers to reduce risk of infection following stem cell transplantation. News release. FDA. April 17, 2023. Accessed May 20, 2026. bit.ly/3UEO3kp

FDA approves first cellular therapy to treat patients with severe aplastic anemia. News release. FDA. December 8, 2025. Accessed May 20, 2026. https://tinyurl.com/yuu377yt

Results from the first-in-human, phase 1 MYTHIC trial (NCT04855656) demonstrated that combining the WEE1 inhibitor zedoresertib with the PYKMT1 inhibitor lunresertib achieved an overall response rate (ORR) of 18.5% via RECIST criteria in patients with CCNE1, FBXW7, and PPP2R1A-altered cancers.1 In patients with resistant/refractory ovarian cancer, the ORR was 33.3% across all dose levels and 50% at the potential recommended phase 2 dose. 
These data were presented by Timothy A. Yap, MBBS, PhD, FRCP, at the 2026 American Association for Cancer Research (AACR) Annual Meeting. Following his presentation, Yap joined CancerNetwork® for a discussion where he highlighted some of the most interesting takeaways from the trial. According to Yap, the disease states evaluated in this trial represent areas of unmet need where no specific standard-of-care options can target these alterations.
Notably, based on results from this trial, the FDA granted fast track designation to lunresertib in combination with zedoresertib in patients with genomic-defined platinum-resistant ovarian cancer.2
Yap is a medical oncologist and physician-scientist, as well as the Random Horne, Jr. Endowed Professor for Cancer Research and vice president and head of Clinical Development in the Therapeutics Discovery Division at UT MD Anderson Cancer Center.
References

1.        Yap TA, Aggarwal R, Fontana E, et al. First data disclosure of the Phase I trial of the first in class combination of WEE1 inhibitor zedoresertib with PKMYT1 inhibitor lunresertib in patients with advanced solid tumors harboring CCNE1, FBXW7, or PPP2R1A genomic alterations. Presented at the 2026 AACR Annual Meeting; April 17-22, 2026; San Diego, CA. Abstract CT022.
2.        Following oral presentation of phase I Data at AACR 2026, Debiopharm announces FDA fast track designation for lunresertib in combination with zedoresertib for genomic-defined platinum-resistant ovarian cancer. News release. Debiopharm. April 20, 2026. Accessed May 4, 2026. https://shorturl.at/n1bWn

Following the 2026 National ICE-T Conference in Charlotte, North Carolina, Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA, and Barry Paul, MD, spoke with CancerNetwork® about high-level takeaways that emerged during the meeting. They discussed how CAR T-cell therapies, bispecific antibodies, and other novel modalities currently fit into the treatment paradigm across multiple myeloma, leukemia, lymphoma, and other hematologic oncology populations. 
The experts first discussed ideas from a session dedicated to innovations in CAR T cells and cellular therapies, with Mahmoudjafari emphasizing ongoing work exploring novel constructs such as dual-targeting chimeric antigen receptors (CARs) that may overcome antigen escape. According to Paul, a need remains for determining appropriate biomarkers to identify patients who are most likely to derive long-term benefit from agents like ciltacabtagene autoleucel (Carvykti).
Regarding another session related to bispecific antibodies and T-cell–engaging agents, Mahmoudjafari described how many new off-the-shelf therapeutic options are challenging clinicians to rethink care delivery models that can provide both high acuity monitoring and outpatient flexibility. Paul also stressed the importance of determining whether fixed-duration therapy with bispecific antibodies may provide similar benefits as indefinite therapy while avoiding the risks of overtreatment.
Looking beyond the most recent meeting in April, Mahmoudjafari and Paul outlined the potential themes of the upcoming National ICE-T Conference in Orlando, Florida, which will take place this July. The next meeting, Mahmoudjafari said, will continue to build upon the field’s shift from innovation to implementation of novel cellular therapies by focusing on operationalizing treatment delivery models across different settings. Paul stated that the meeting in Orlando will help further delineate new targets for developing therapies that may be more effective and less toxic for patients.
Mahmoudjafari is a clinical pharmacy manager in the Division of Hematologic Malignancies and Cellular Therapeutics at the University of Kansas Health System. Paul is an assistant professor of cancer medicine at Atrium Health Levine Cancer Institute of Wake Forest University School of Medicine.

In a conversation with CancerNetwork®, Diane Simeone, MD, discussed the implications of daraxonrasib demonstrating meaningful improvements in survival among patients with metastatic pancreatic ductal adenocarcinoma (PDAC) in the phase 3 RASolute 302 trial (NCT06625320). Topline findings from the trial showed that the novel multiselective RAS(ON) inhibitor approximately doubled the median overall survival (OS) compared with investigator’s choice of chemotherapy, with survival benefits extending to those with different RAS mutations and RAS wild-type disease.
Simeone spoke about the significance of these results in the context of the pancreatic cancer field, breaking down how daraxonrasib’s mechanism of action as a pan-RAS inhibitor may open a “new fronter” beyond standard-of-care chemotherapy and platinum-based regimens. She also touched upon the prominent toxicities that have emerged with daraxonrasib, including rashes, while emphasizing the balancing of risk and benefit as part of further optimizing RAS therapeutics.
The discussion also highlighted strategies for expanding genetic testing for patients with pancreatic cancer, as Simeone described the importance of receiving second opinions at comprehensive cancer centers where multidisciplinary teams can guide patients towards personalized treatment plans. She also mentioned how initiatives such as the Pancreatic Cancer Early Detection (PRECEDE) Consortium represent viable opportunities for continuing to elevate the quality of care for patients.
“This has been a Holy Grail type of thing, where people have been wanting to target KRAS but it’s been a challenge. This has been a breakthrough,” Simeone said regarding the results seen with daraxonrasib. “While the effect is dramatic in patients with metastatic cancer—and unfortunately that’s still half of patients who walk in the door with pancreatic cancer—applying this therapy to stage I cancer could be even more profound and drive cures. Investment in early detection, partnered with these advances in therapeutics, is where we will see the most significant progress in increasing survival rates.”
Simeone is the director of the Moores Cancer Center at University of California San Diego Health.
Reference

Daraxonrasib demonstrates unprecedented overall survival benefit in pivotal phase 3 RASolute 302 clinical trial in patients with metastatic pancreatic cancer. News release. Revolution Medicines. April 13, 2026. Accessed April 29, 2026. https://tinyurl.com/44t5vh5d