By Udhayvir Singh Grewal, MD
GI/Neuroendocrine Medical Oncologist and Assistant Professor of Medical Oncology, Winship Cancer Institute of Emory University School of Medicine
Dr. Grewal contributed this guest update to share clinical and research highlights from the 2026 ASCO Annual Meeting.
The ASCO Annual Meeting 2026 is always a special meeting, but this year was particularly impactful as we saw a critical breakthrough in pancreatic cancer treatment (Daraxonrasib)- the greatest advance in decades for a difficult-to-treat cancer. This gives hope to our patients with pancreatic cancer (and beyond) that science and clinical trials can truly make the impossible possible! This year, we also saw many notable and important studies focused on neuroendocrine neoplasms, something that I am always on the lookout for. It was also great to see a dedicated neuroendocrine tumor session at a major oncology meeting like ASCO; a much-welcome step to promote neuroendocrine neoplasms and bring more attention to this important disease space. Editor’s Note: Daraxonrasib is for pancreatic ductal adenocarcinoma (“pancreatic cancer”), not pancreatic neuroendocrine tumors. These are two different types of cancer that both occur in the pancreas.
Here, I summarize some key abstracts and sessions that particularly stood out to me.
Alpha Radioligand Therapy Continues to Make a Splash!
Alpha radioligand therapy remains one of the most exciting areas in well-differentiated neuroendocrine tumors. Thorvardur (Thor) Halfdanarson, MD (Mayo Clinic), presented cohort-level safety and efficacy results from the phase 1/2a study of [212Pb]VMT-α-NET in advanced SSTR2-positive neuroendocrine tumors. Among 56 treated patients, there were no dose-limiting toxicities, no grade 5 adverse events, no treatment-related discontinuations, no serious renal events, and no clinically meaningful treatment-related myelosuppression (bone marrow suppression). In the efficacy-evaluable cohort, objective responses were seen in 9 of 23 patients treated at the 5 mCi dose level, corresponding to a 39% objective response rate, including 8 confirmed responses. Both patients treated at the 2.5 mCi dose level continued to have stable disease after two years of follow-up. These early data are very encouraging. Alpha radioligand therapy may offer a more potent form of radioligand treatment, and it is exciting to see multiple agents in this space moving forward. Long term follow-up will be critical to better understand the durability of response and late toxicities.
DLL3 Continues to Move the Needle Forward
Neuroendocrine carcinoma (NEC) remains an area of major unmet need. Currently, chemotherapy represents the standard of care, which is associated with suboptimal outcomes and an overall poor prognosis. Delta-like ligand 3 (DLL3)-targeted therapies are quickly emerging as a promising therapeutic strategy in this space. Dr. Chuanhua Zhao (Fifth Medical Center, Chinese PLA General Hospital) presented results from a randomized phase II dose-optimization study of alveltamig (ZG006), a trispecific T-cell engager targeting DLL3/DLL3/CD3, in patients with refractory NEC. A total of 64 patients were randomized to receive either 10 mg or 30 mg every two weeks after a 1 mg priming dose. The confirmed objective response rate was 21.9% in the 10 mg group and 37.5% in the 30 mg group, while disease control rates were 40.6% and 62.5%, respectively. Responses were seen across several extrapulmonary neuroendocrine carcinoma sites, including cervical, gallbladder, gastric, rectal, and colon primaries.
The biomarker data were particularly notable. Among patients with DLL3 expression in at least 50% of tumor cells, the 30 mg dose achieved a confirmed objective response rate of 56.3%, a disease control rate of 75.0%, and a median progression-free survival of 8.41 months. Cytokine release syndrome was common but mostly grade 1-2, with only four grade 3 events and no grade 5 treatment-related adverse events. This is much-needed progress for patients with refractory neuroendocrine carcinomas. The high response rate in DLL3-positive tumors suggests that biomarker selection may be important as these agents move forward in development.
CAR T-Cell Therapy Enters the Chat
Chimeric Antigen Receptor (CAR) T-cell therapy has revolutionized care in hematological malignancies but is still early in development for solid tumors. As we continue to develop these therapies for solid cancers, it is encouraging to see neuroendocrine tumors included in these efforts. Jennifer Eads, MD (University of Pennsylvania), presented preliminary data from an ongoing phase 1/2 study of CHM-2101, an autologous cadherin 17 (CDH17)-directed CAR T-cell therapy, in relapsed or refractory gastrointestinal cancers, including gastric cancer, colorectal cancer, and certain well-differentiated intestinal neuroendocrine tumors, such as tumors that start in the ileum, jejunum, cecum, distal colon, or rectum.
As of the data cutoff, 13 patients had enrolled, with 9 treated across the first two dose levels. Manufacturing was successful in all 11 attempted runs, and CHM-2101 demonstrated expansion and persistence in peripheral blood after infusion. Most adverse events were grade 1-2. Aside from expected cytopenias related to lymphodepleting chemotherapy, grade 3 treatment-related events included cytokine release syndrome and enterocolitis in one patient each. No grade 4 or 5 treatment-related adverse events or dose-limiting toxicities were reported. While these data remain very early, the feasibility of CAR T-cell manufacturing, expansion, and persistence in patients with advanced GI cancers, including neuroendocrine tumors, is an important first step. We will need more mature efficacy data to understand the potential role of this strategy.
MTAP Loss in Neuroendocrine Tumors (NETs): A New Therapeutic Avenue?
Precision oncology has truly transformed outcomes across malignancies. While the role of molecularly matched therapies in neuroendocrine tumors remains limited, there are several ongoing efforts aimed at making personalized therapies a viable reality. Rohit Thummalapalli, MD (Memorial Sloan Kettering Cancer Center), presented a large genomic and biomarker analysis of MTAP deficiency across gastrointestinal cancers.
Specifically, the pancreatic neuroendocrine tumor and small intestinal neuroendocrine tumor cohort findings were particularly interesting. MTAP genomic deletion was identified in 7.4% of PanNETs (PanNETs) overall but was enriched in grade 3 PanNETs, with a prevalence of 19.4%. By immunohistochemistry, MTAP deficiency was seen in 25% of PanNETs and, strikingly, in 71% of small intestinal NETs despite no detectable MTAP genomic deletions in small intestinal neuroendocrine tumors. These findings suggest that MTAP loss may be more common in neuroendocrine tumors than genomic sequencing alone would indicate, possibly due to non-genomic mechanisms of MTAP silencing. With several PRMT5 and MAT2A inhibitors in therapeutic development targeting MTAP loss, this may become an important biomarker space for neuroendocrine tumor clinical trials.
Long-Term Safety of PRRT
As we continue to use radioligand therapy earlier and more frequently in neuroendocrine tumors, optimizing risk stratification for long-term hematologic toxicity remains critically important. Deevyashali Parekh, MBBS (SUNY Upstate Medical University) presented the largest analysis to date evaluating therapy-related myeloid neoplasms after 177Lu-DOTATATE in patients with neuroendocrine tumors.
Using the TriNetX research network, this multicenter real-world analysis included 1,811 patients treated with 177Lu-DOTATATE. Therapy-related myeloid neoplasms, including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), were uncommon but clinically meaningful, occurring in 2.88% of patients. MDS developed in 2.05% of patients, while AML developed in 0.83% of patients. On multivariable analysis, older age and baseline chronic kidney disease were associated with increased risk. Interestingly, prior temozolomide exposure and 177Lu-DOTATATE retreatment were not associated with increased risk. These data are important because they provide much-needed real-world context for counseling patients receiving PRRT. We hope that ongoing studies evaluating the role of clonal hematopoiesis of indeterminate potential (CHIP) will help refine risk prediction in this setting.
A Dedicated NET Session at ASCO!
One of the highlights of ASCO 2026 was a dedicated session focused on neuroendocrine cancers. This is an important and welcome step for a disease space that has historically had limited visibility at large oncology meetings.
The session highlighted several cutting-edge areas in neuroendocrine cancer research. Simron Singh, MD, MPH (Sunnybrook Hospital, Canada), discussed targeted alpha particle therapies and where the field stands now. Jennifer Chan, MD, MPH (Dana-Farber Cancer Institute, Harvard Medical School), reviewed DLLe-targeted approaches and treatment considerations. Thorvardur Halfdanarson, MD (Mayo Clinic), discussed emerging targets in PanNETs. The session concluded with a panel discussion moderated by Dr. Chan, with Drs. Singh and Halfdanarson as panelists. It is great to see ASCO create space for focused discussion on NETs, especially around novel therapeutic targets and treatment strategies.
Looking Ahead
Overall, ASCO 2026 highlighted the growing momentum and progress in our field. We are seeing important progress across multiple fronts; there remains a lot of work to do, but the direction is clear. Neuroendocrine cancer research is becoming increasingly molecular and personalized, which is very exciting. To think about what this means for our patients and their loved ones fills my heart with hope and pride.
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NETRF’s Impact on Research
Several themes in this ASCO update highlight areas where NETRF has helped advance neuroendocrine cancer research, including MTAP loss, alpha-emitting peptide receptor radionuclide therapy, DLL3-targeted research for extrapulmonary neuroendocrine carcinoma, and foundational work on CDH17-directed CAR T-cell therapy. For our community, these connections are encouraging examples of how sustained research funding can help turn scientific discoveries into new biomarkers, treatment targets, and clinical trial opportunities.
NETRF is grateful to Dr. Grewal for contributing this guest update. His summary reflects his perspective on selected highlights from ASCO 2026 and brings emerging research conversations to our community.