Researchers from Dana-Farber Cancer Institute are showcasing significant advances in cancer treatment at the 2025 American Association for Cancer Research (AACR) Annual Meeting in Chicago. The event, running from April 25-30, features numerous studies highlighting progress in treating head and neck cancer, metastatic breast cancer, lung cancer, and other malignancies.
Pembrolizumab Shows Promise in Head and Neck Cancer
Dr. Ravindra Uppaluri, Director of Head and Neck Surgical Oncology at Dana-Farber, will present results from the Phase 3 KEYNOTE-689 study examining neoadjuvant and adjuvant pembrolizumab plus standard of care in patients with resectable locally advanced head and neck squamous cell carcinoma (LA HNSCC). The presentation, scheduled for Sunday, April 27, will be followed by a press conference where Dr. Uppaluri will discuss the findings in detail. Dr. Robert Haddad, Chief of the Division of Head and Neck Oncology, serves as the senior author of this important study.
Personalized Cancer Vaccines Address Tumor Heterogeneity
In the opening plenary session, Dr. Catherine J. Wu will explore how personalized cancer vaccines can harness the adaptive immune system to overcome challenges in treating evolving tumor ecosystems. Her presentation, "Addressing tumor heterogeneity: personalized cancer vaccines," represents a cutting-edge approach to cancer immunotherapy that could potentially transform treatment paradigms.
Novel Combination Shows Efficacy in Metastatic Breast Cancer
Dr. Elia Segui from Dana-Farber's Breast Oncology Center will present findings from a single-arm phase 1 trial combining avutometinib (a RAF/MEK inhibitor), abemaciclib (a CDK4/6 inhibitor), and fulvestrant in patients with hormone receptor-positive, HER2-negative metastatic breast cancer who previously progressed on CDK4/6 inhibitor therapy.
"Preclinical studies suggested that avutometinib could reverse resistance to CDK4/6 inhibitors and enhance their anti-cancer effects," explained Dr. Segui. The combination demonstrated a manageable safety profile and showed promising anti-cancer activity in patients with CDK4/6 inhibitor-resistant disease. A phase 2 trial is currently underway to further evaluate clinical efficacy.
Innovative RAS Inhibitors for Lung Cancer
Dr. Jia Luo, a thoracic oncologist at Dana-Farber, will present two significant studies on novel RAS inhibitors in non-small cell lung cancer (NSCLC):
The first study examined daraxonrasib, a RAS inhibitor targeting multiple RAS mutations including KRAS G12D and KRAS G12V. Analysis of circulating tumor DNA (ctDNA) from plasma samples revealed complete clearance of RAS mutants in 89% of treatment responders and 70% of patients with stable disease, but in none of the patients whose disease progressed. These findings suggest that response to daraxonrasib correlates with complete clearance of ctDNA for multiple RAS mutations.
Dr. Luo will also present early results from an ongoing phase 1 trial combining divarasib (a next-generation KRAS G12C inhibitor) with migoprotafib (a SHP2 inhibitor) in KRAS G12C-mutant NSCLC patients. Among 48 patients who had not received prior KRAS G12C-targeted therapy, the objective response rate was 43.8%, with observable declines in ctDNA levels, indicating promising clinical activity.
FGFR Inhibition Shows Promise in Rare Gastrointestinal Stromal Tumors
Dr. Priscilla Merriam, Clinical Director of Dana-Farber's Sarcoma Center, will present results from preclinical research and a phase 2 clinical trial evaluating FGFR inhibitors in succinate dehydrogenase deficient gastrointestinal stromal tumor (SDHd GIST).
In the clinical trial, 24 patients with SDHd GIST received regaratinib, an FGFR inhibitor. After a median follow-up of 17.8 months, 10 patients achieved partial responses and 12 had stable disease. "These findings strongly support targeting FGFR signaling in this specific patient population," noted Dr. Merriam.
Novel Combination for Advanced Salivary Gland Cancer
Dr. Glenn J. Hanna, Director of the Center for Salivary and Rare Head and Neck Cancers, will present results from a phase 2 non-randomized clinical trial testing elraglusib (a glycogen synthase kinase 3 beta inhibitor) plus chemotherapy with or without pembrolizumab in patients with advanced salivary gland cancers.
The combination with immunotherapy was well-tolerated, with 18% of non-adenoid cystic carcinoma cases showing anti-tumor activity. These results suggest further investigation of this combination is warranted in selected populations with this rare cancer type, which currently has limited treatment options.
Digital Health Coaching Improves Cancer Survivor Outcomes
Dr. Alexi Wright, Director of Gynecologic Oncology Outcomes Research, will share interim analysis results from the Comprehensive Outcomes for After Cancer Health (COACH) study. This innovative research explores a six-month digital health coaching program for patients within one year of primary treatment or during ongoing treatment for metastatic disease.
The analysis of 177 patients who completed initial and six-month assessments showed trending improvements in physical function across diverse groups, regardless of race, age, cancer type, and study site (with the exception of one site that included only patients with metastatic breast cancer).
Recognition of Dana-Farber Researchers
Several Dana-Farber researchers received prestigious AACR Scientific Achievement awards at the meeting:
- Dr. Toni Choueiri, Director of the Lank Center for Genitourinary Oncology, received the AACR-Waun Ki Hong Award for Outstanding Achievement in Translational and Clinical Cancer Research
- Dr. Matthew L. Meyerson, Director of the Center for Cancer Genomics, received the James S. Ewing-Thelma B. Dunn Award for Outstanding Achievement in Pathology in Cancer Research
- Dr. Alice T. Shaw, Chief of Strategic Partnerships, received the Joseph H. Burchenal Award for Outstanding Achievement in Clinical Cancer Research
Additionally, Drs. Bradley Bernstein, A. Thomas Look, and William R. Sellers were recognized as Fellows of the AACR Academy Class of 2025.
The breadth and depth of research presented by Dana-Farber investigators at AACR 2025 underscore the institution's commitment to advancing cancer treatment through innovative clinical trials, targeted therapies, and multidisciplinary approaches that aim to improve patient outcomes across a wide spectrum of cancer types.
