Researchers from Memorial Sloan Kettering Cancer Center (MSK) presented new studies related to a range of cancer types at the European Society for Medical Oncology (ESMO) Congress 2025, held October 17 to 21 in Berlin.
Highlights included the latest updates on three phase 1 trials testing innovative treatment approaches for certain patients with advanced solid tumors, including lung cancer and pancreatic cancer . Additionally, MSK researchers presented new insights about solid tumors with a defect called mismatch repair deficiency that may guide personalized treatments.
First Report From the Phase 1 Trial of Iza-bren for Lung and Other Cancers
Thoracic medical oncologist and early drug development specialist Helena Yu, MD , presented the first results for the experimental drug izalontamab brengitecan (iza-bren/BL-B01D1). The drug was tested in non-small cell lung cancer (NSCLC) and other solid tumors with certain mutations. The trial is taking place at 22 locations in the United States, and Dr. Yu is principal investigator at MSK.
Iza-bren is a type of treatment called a bispecific antibody-drug conjugate (ADC). Unlike many other ADCs that target a single mutation driving cancer growth, iza-bren is a dual agent: It seeks out cells that carry mutations in the genes EGFR and HER3. It then delivers a payload of chemotherapy directly to the cancer cells.
The drug has shown early promise in treating tumors with these mutations, especially NSCLC. So far, 107 patients have received the treatment. Among the 10 patients with NSCLC who received the optimal dose, 75% responded, meaning that their tumors shrank. Low blood counts were the most common side effect seen across the study, but they were treatable.
This trial is ongoing, and more studies of the drug are planned. Learn more about the study .
Combining Chemotherapy With Stem Cell Transplant Shows Promise for Inherited Pancreatic Cancer
Patients with advanced pancreatic cancers driven by inherited mutations in the genes BRCA 1/2 or PALB2 often develop resistance to multiple lines of chemotherapy, leaving them with few options.
Gastrointestinal medical oncologist Kenneth Yu, MD , presented a poster summarizing interim results from the phase 1 trial, called SHARON. This novel study is evaluating the safety and efficacy of using certain targeted chemotherapy drugs along with an autologous stem cell transplant (a transplant using the patient's own blood stem cells). The 11 patients enrolled so far had stage 3 pancreatic cancer and carried one of these inherited mutations.
The trial is a collaboration between gastrointestinal medical oncologists and transplant specialists at MSK and Massachusetts General Hospital, with MSK enrolling a majority of patients. After the patient's stem cells are collected, patients receive chemotherapy followed by stem cell transplantation. The whole treatment is repeated six weeks later.
Among the five patients whose disease was stable before the trial or who responded to the treatment, the average time it took for their disease to progress was 14.2 months. Two patients were still disease-free at 23 and 48 months after treatment. The treatment did not have any unexpected side effects.
MSK aims to recruit 15 more patients for the continuing trial . Learn more about this study .
For Solid Tumors With MMRd, the Mechanism Influences Survival After Immunotherapy Treatment
Current guidelines say that patients with solid tumors should have their tumors tested for conditions called mismatch repair deficiency (MMRd) or microsatellite instability-high (MSI-H) to determine whether they are likely to benefit from immunotherapy drugs called immune checkpoint inhibitors. Now a new study, led by researchers at MSK, has found that the specific mechanisms that cause MMRd or MSI-H can affect how well these drugs actually work.
The study was led by Benoît Rousseau, MD, PhD , Assistant Member of the Gastrointestinal Oncology Service, and presented by Violaine Randrian, MD, PhD , a visiting scientist from France. The research team studied almost 2,000 patients tested at MSK and analyzed a database of more than 13,000 patients who had testing done at a commercial lab. In addition to assessing how well these patients responded to immunotherapy, researchers looked at the patient's cancer type and the particular mechanism leading their tumors to be MMRd or MSI-H.
Importantly, they found that the mechanism that caused these conditions affected how well the treatments worked and how long patients survived. For example, patients with MSI-H tumors or the inherited condition called Lynch syndrome were mostly likely to benefit for a long time. The type of cancer that patients had also affected how well these treatments worked.
The researchers say these findings suggest that it's essential to assess patients for both MMRd and MSI-H, to better tailor personalized immunotherapy treatment. Learn more about this study.
New Targeted Therapy for MSI-H/MMRd Tumors Appears To Be Safe and Effective in Early Study
MSK gastrointestinal medical oncologist Michael Foote, MD , presented preliminary results from the first in-human phase 1 study of a drug called HRO761 in patients with advanced MSI-H/MMRd tumors that had progressed on other therapies, including immunotherapy, chemotherapy, and targeted therapies. HRO761 is a new type of targeted therapy that blocks a protein called Werner helicase.
The analysis included 57 patients:
- 58% had colorectal cancers .
- 11% had uterine (endometrial) cancers .
- 11% had gastric/gastroesophageal junction cancers .
- 21% had other solid tumor types.
Preliminary results showed that nearly 80% of patients with colorectal cancer had their disease controlled. Furthermore, after one month of taking the drug, about 70% of patients with colorectal cancers had no evidence of tumor cells in their blood. The drug had few serious side effects and none of the patients had to stop taking it due to complications.
The phase 1 study
