Memorial Sloan Kettering Cancer Center (MSK) researchers presented practice-changing advances in new treatment approaches for a range of cancer types at the 2025 ASCO Annual Meeting held May 30 to June 3, 2025, in Chicago.
Highlights included breakthroughs for patients with advanced gastric cancer, lung cancer, Lynch syndrome-related cancer and salivary gland cancer. Additionally, the first-ever CAR T cell trial for patients with light chain amyloidosis is showing promising results.
Gastric and Gastroesophageal Cancer: Immunotherapy Plus Chemotherapy Combination Provides Curative Potential
The combination of perioperative durvalumab, a PD-L1 blocker, plus standard-of-care fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) significantly improved event-free survival (EFS) in patients with resectable stage 2-4a gastric/gastroesophageal junction cancer.
Yelena Janjigian, MD, Chief of the Gastrointestinal Medical Oncology Service at MSK, presented efficacy and safety results from the second pre-planned interim analysis of the global phase 3 MATTERHORN trial (NCT04592913) in a plenary session. Dr. Janjigian is the global principal investigator and first author of the groundbreaking study published simultaneously in The New England Journal of Medicine.
In total, 948 patients were randomized to receive durvalumab or placebo intravenously every four weeks plus FLOT chemotherapy intravenously every two weeks on days 1 and 15 for four cycles (two cycles neoadjuvant and two cycles adjuvant), followed by durvalumab or placebo intravenously for 10 additional cycles. There were 474 participants in the durvalumab group and 474 in the placebo group.
The EFS rate was significantly higher in the durvalumab plus FLOT group compared to the placebo plus FLOT group, with a hazard ratio (HR) of 0.71 (p < 0.001). Median EFS was not reached in the durvalumab group and was 33 months in the placebo group. The 24-month EFS rate in the durvalumab group was 67%, significantly higher than 59% in the placebo group.
Rates of grade 3 or 4 treatment-related adverse events (TRAEs) were similar between treatment arms. Overall survival (OS) results showed an encouraging trend, with a median OS not reached in the durvalumab group versus 47 months for the placebo group (HR = 0.78, p = 0.025). Researchers will continue to follow OS through the final analysis.
“This is the first global, randomized phase 3 trial to demonstrate a superior and clinically meaningful improvement in EFS with an immunotherapy combination compared to the current standard of care in this patient population,” said Dr. Janjigian. “The results underscore the curative potential for this modern, first-line triplet therapy and support it becoming a new global standard.”
Read ASCO 2025 Abstract 487794. The study was sponsored by AstraZeneca. Access disclosures for Dr. Janjigian. Learn more about MSK gastric and gastroesophageal junction cancer clinical trials.
EGFR-Mutated NSCLC: Neoadjuvant Osimertinib Improves Major Pathologic Response Versus Chemotherapy Alone In Patients with Resectable Disease
Neoadjuvant osimertinib — with or without chemotherapy — resulted in a significant improvement in the major pathologic response over chemotherapy alone in patients with resectable, EFGR-mutated non-small cell lung cancer (NSCLC).
MSK thoracic medical oncologist Jamie Chaft, MD, FASCO, presented results for the phase 3 NeoADAURA trial (NCT04351555). Dr. Chaft was one of three principal investigators for the international study, which took place at 159 locations.
Adjuvant osimertinib, a third-generation EGFR tyrosine kinase inhibitor, is the current standard of care for patients with resected stages 1B-3A EGFR-mutated NSCLC. The NeoADAURA trial evaluated whether neoadjuvant osimertinib could improve pathological and long-term outcomes.
A total of 358 patients were randomized 1:1:1 to three study arms: neoadjuvant osimertinib plus cis/carboplatin plus pemetrexed (121 patients); neoadjuvant osimertinib monotherapy (117 patients); or placebo plus chemotherapy (120 patients).
Adjuvant osimertinib was offered to all patients who completed surgery, and 80% received it. After neoadjuvant treatment, 92%, 97%, and 89% of patients, respectively, underwent surgery.
Major pathologic response was defined as having 10% or fewer residual cancer cells in the primary tumor as assessed by post-surgical pathology. The major pathologic responses were 26% for the osimertinib plus chemotherapy group and 25% for the osimertinib monotherapy group, significantly higher than 2% in the control arm (placebo plus chemotherapy). The odds ratios were 19.8 (p<0.0001) and 19.3 (p<0.0001), respectively.
The interim EFS was 15% mature and trending in favor of both osimertinib arms. In the neoadjuvant treatment period, grade 3 or higher all-cause adverse events occurred in 36%, 13%, and 33% of patients, respectively, and adverse events leading to any treatment discontinuation occurred in 9%, 3%, and 5% of patients, respectively. No patients died within 30 days of surgery.
“When neoadjuvant treatment is recommended, osimertinib should be considered as part of that treatment for patients with EGFR-mutated NSCLC,” said Dr. Chaft. “The NeoADAURA results further emphasize the importance of biomarker testing and personalization of treatment through all phases of lung cancer care.”
Read ASCO 2025 Abstract 495272. The study was sponsored by AstraZeneca. Access disclosures for Dr. Chaft. Learn more about MSK clinical trials for patients with NSCLC.
EGFR-Mutated NSCLC: Zipalertinib Demonstrates Potential for Patients with Advanced Disease
Zipalertinib, a novel, oral EGFR tyrosine kinase inhibitor, demonstrated efficacy with manageable side effects in patients with NSCLC with EGFR exon 20 insertions (ex20ins) who had previously received platinum-based chemotherapy, including those who also received prior amivantamab.
MSK thoracic medical oncologist Helena Yu, MD, presented the primary results from phase 2b of the international, open-label, REZILIENT trial (NCT04036682).
As of the data cutoff on December 10, 2024, 176 patients with progression on prior treatment with platinum-based chemotherapy were enrolled in two parallel cohorts: 125 who had not received amivantamab and 51 who had received amivantamab previously.
The objective response rate (ORR) among all 176 patients was 35% with a median duration of response of 8.8 months. The median PFS was 9.5 months.
The ORR was 40% for patients with no amivantamab treatment history and 30% for those who had received amivantamab. Among 51 patients who had also received amivantamab, the ORR was 30% for the group of 30 patients who had no other ex20ins-directed therapy and 14% for those who had received other ex20-ins drugs, including mobocertinib, sunvozertinib, BLU-451, or poziotinib. The systemic ORR was 31% among all patients with brain metastases.
Most TRAEs were grade 1 or 2. The most common were paronychia, rash, anemia, diarrhea, dry skin, nausea, and stomatitis.
“There is an unmet need for well-tolerated oral therapies with durable clinical benefit for patients with EGFR exon 20-mutant NSCLC who experience progression on platinum-based chemotherapy,” said Dr. Yu. “These results support zipalertinib as a potential new treatment option for this patient population, including those whose disease did not improve or worsened on amivantamab.”
The confirmatory phase 3 REZILIENT 3 study is ongoing (NCT05973773).
Read ASCO Abstract 8503. The study was sponsored by Cullinan Therapeutics, Inc. Access disclosures for Dr. Yu. Learn more about MSK NSCLC clinical trials.
Other Notable MSK Research News from ASCO 2025:
- Lynch-Related Advanced Cancers: MMR Variants Predict Responses to Immune Checkpoint Blockade. Violaine Randrian, MD, PhD, a visiting investigator in the Luis Diaz Jr. Lab, presented results of a retrospective study of response and survival outcomes for patients with Lynch-syndrome-related advanced cancers to immune checkpoint blockade stratified by germline variant. Dr. Randrian’s advisor for this study was Benoît Rousseau, MD, PhD. She also collaborated with Zsofia Stadler, MD, Lead of Inherited Gastrointestinal Cancer Genomics at MSK. Patients included in the study had received at least one dose of immune checkpoint blockade and consented to tumor sequencing via the MSK-IMPACT® assay. Microsatellite instability (MSI) and mismatch repair (MMR) status were assessed via MSISensor score and immunohistochemistry staining, respectively. The most represented tumor types among the 186 patients were colorectal (35%), urothelial (14%), pancreatic/biliary (13%), upper gastrointestinal (11%), and endometrial (11%). The overall ORR was 58%, including 35% with a complete response and higher rates in patients with MLH1 and MSH2 variants. Patients with germline PMS2 variants were more likely to have MMR-proficient/microsatellite stability tumors, which do not respond to immune checkpoint blockade. Germline PMS2 patients with confirmed MSI-high tumors had similar clinical outcomes to other patients. The results suggest that all Lynch-related advanced tumors should be tested for MMR and MSI status to predict response to immunotherapy. Read ASCO Abstract 10504. The study was supported by funding from Swim Across America; Fondation Nuovo Soldati; Institut Servier; Mobilite chercheurs Ligue Contre Le Cancer; Bourse Tournut SNFGE; and Universite de Poitiers, CHU de Poitiers. Learn more about MSK clinical trials for patients with colorectal cancer, urothelial cancer, and pancreatic cancer.
- Advanced Salivary Gland Cancer: Lenvatinib plus pembrolizumab showed promising activity in patients with recurrent or metastatic salivary gland cancers. Principal investigator Alan L. Ho, MD, PhD, Chief of the Head and Neck Oncology Service at MSK, gave a poster presentation of results from the investigator-initiated phase 2 trial (NCT04209660). The trial evaluated whether VEGFR inhibition with lenvatinib would enhance immune checkpoint-induced responses in patients with incurable salivary gland cancers. Among 26 patients, nine had acinic cell carcinoma, eight had salivary duct carcinoma, four had myoepithelial carcinoma, two had mucoepidermoid carcinoma, and three had other salivary cancer diagnoses. The ORR for all 26 patients was 19%. Remarkably, four of nine patients (44%) with acinic cell carcinoma had a major response, and five (56%) had stable disease. These results are noteworthy given that acinic cell carcinoma is a chemotherapy-refractory tumor with no standard treatment options. Across all histologies, six deaths occurred, of which four may have been treatment-related, none of which occurred in patients with acinic cell carcinoma. Results for the adenoid cystic carcinoma cohort were reported previously. Read ASCO 2025 Abstract 6103. Merck Sharp & Dohme, LLC, provided lenvatinib and pembrolizumab for the trial. Access disclosures for Dr. Ho. Learn more about MSK clinical trials for patients with salivary gland cancer.
- Light Chain Amyloidosis: First CAR T Cell Trial Shows Rapid and Deep Responses. Bone marrow transplant specialist and cellular therapist Heather Landau, MD, presented early results from the first-ever U.S. trial of the CAR T cell therapy NCX-201 in relapsed or refractory light chain (AL) amyloidosis. This rare plasma cell disease results in life-threatening organ dysfunction and death if left untreated. NCX-201 is a BMCA-directed CAR T cell therapy that showed promising efficacy with a favorable toxicity profile in a multiple myeloma trial that allowed the enrollment of patients with AL amyloidosis. The phase 1/2 NEXICART-2 study (NCT06097832) is currently recruiting at seven U.S. locations and seeks to enroll 40 patients. Among the first 10 patients, all normalized their pathologic disease markers (free light chain or monoclonal protein) by day 15 following treatment. Seven achieved a complete hematologic response (CR). Among patients who have not yet achieved CR, all had no residual disease in the bone marrow and will likely evolve to CR. Adverse events included low-grade cytokine release syndrome and grade 3 or grade 4 neutropenia, both in eight patients. There was only one case of febrile neutropenia, but no associated infection. No patients experienced neurotoxicity, cardiac toxicity, and no treatment-related deaths occurred. No relapses have occurred to date. These results suggest that NXC-201 may become a beneficial treatment option for this patient population. Read ASCO 2025 Abstract 7508. The study was sponsored by Nexcella, Inc. Access disclosures for Dr. Landau. Learn more about MSK clinical trials for patients with amyloidosis.