Head and Neck, Breast, Lung and Survivorship Studies Headline Dana-Farber Research at AACR Annual Meeting 2025

Numerous studies conducted by researchers at Dana-Farber Cancer Institute report progress for cancers including head and neck cancer, metastatic breast cancer, and lung cancer. The results of these studies, along with dozens of others led by Dana-Farber faculty, will be presented at this year’s American Association for Cancer Research (AACR) Annual Meeting held April 25-30, 2025, in Chicago.

The institute’s leading experts and researchers will present findings across a spectrum of diseases, underscoring their dedication to driving innovation, improving patient outcomes and changing lives everywhere.

Ravindra Uppaluri, MD, PhD, director of Head and Neck Surgical Oncology, will present the study “Neoadjuvant and adjuvant pembrolizumab plus standard of care (SOC) in resectable locally advanced head and neck squamous cell carcinoma (LA HNSCC): Phase 3 KEYNOTE-689 study” in Clinical Trials Plenary Session CT001 on Sunday, April 27, 2025, from 2:00-2:15 p.m. ET / 1:00-1:15 p.m. CT. The senior author is Robert Haddad, MD, chief of the Division of Head and Neck Oncology and the McGraw Chair in Head and Neck Oncology at Dana-Farber.

In addition, Uppaluri will discuss the study in a press conference on Sunday, April 27, from 12:00 p.m. to 1:00 p.m. ET / 11:00 a.m. to 12:00 p.m. CT.

In the opening plenary at the Annual Meeting, Catherine J. Wu, MD, FAACR, will present “Addressing tumor heterogeneity: personalized cancer vaccines,” exploring how cancer vaccines might be used to harness the adaptive immune system to overcome the challenges associated with treating a continuously evolving tumor ecosystem. Session PL02 will take place on Sunday, April 27, 2025, from 12:01 p.m. to 12:28 p.m. ET / 11:01 a.m. to 11:28 a.m. CT.

AACR Scientific Achievement awards presented during the Annual Meeting honored Toni Choueiri, MD, director of the Lank Center for Genitourinary Oncology at Dana-Farber, with the AACR-Waun Ki Hong Award for Outstanding Achievement in Translational and Clinical Cancer Research; Matthew L. Meyerson, MD, PhD, FAACR, the Charles A. Dana Chair in Human Cancer Genetics and director of the Center for Cancer Genomics at Dana-Farber, with the James S. Ewing-Thelma B. Dunn Award for Outstanding Achievement in Pathology in Cancer Research; and Alice T. Shaw, MD, PhD, chief of strategic partnerships and a physician in Dana-Farber’s thoracic oncology program, with the Joseph H. Burchenal Award for Outstanding Achievement in Clinical Cancer Research.

In addition, Bradley Bernstein, MD, PhD, A. Thomas Look, MD, and William R. Sellers, MD, were recently recognized as Fellows of the AACR Academy Class of 2025.

Other notable research from Dana-Farber includes:

Combination therapy shows promise in phase 1 results for a subgroup of patients with metastatic breast cancer

Elia Segui, MD, an advanced research fellow in the Breast Oncology Center, will share results of a single-arm phase 1 trial (led by Associate Director of Breast Oncology Clinical Research Adrienne Waks, MD) of a combination of two targeted therapies plus hormone therapy in patients with hormone receptor (HR)-positive, human estrogen receptor 2 (HER2)-negative metastatic breast cancer. The medicines combine avutometinib, a RAF/MEK inhibitor, abemaciclib, a CDK4/6 inhibitor and the hormone therapy fulvestrant. The combination is informed by preclinical studies that suggest that avutometinib can reverse resistance to CDK4/6 inhibitors and enhance their anti-cancer effects. The study enrolled patients who had previously progressed on a CDK4/6 inhibitor and aimed to determine safety and find a maximum tolerated dose. The combination showed a manageable safety profile and signs of anti-cancer effects in patients with cancer that was resistant to CDK4/6 inhibitors. A single-arm phase 2 trial is ongoing to evaluate clinical efficacy in this patient group.

Segui will share the results of this study, titled “A single-arm phase 1 trial of avutometinib (RAF/MEK inhibitor), abemaciclib (abema) and fulvestrant in CDK4/6 inhibitor (CDK4/6i)-pretreated patients (pts) with HR+ metastatic breast cancer (MBC),” at the Phase 0 and Phase 1 Clinical Trials Poster Session CT028 on Monday, April 28, 2025, from 10:00 a.m. to 1:00 p.m. ET / 9:00 a.m. to 12:00 p.m. CT.

Findings from two studies of novel RAS inhibitors in lung cancer presented

Jia Luo, MD, a thoracic oncologist, will share findings from an exploratory analysis of data from a phase 1 clinical trial of daraxonrasib, a RAS inhibitor that targets multiple RAS mutations, including KRAS G12D and KRAS G12V. The study examined circulating tumor DNA (ctDNA) from plasma samples collected from patients with advanced non-small-cell lung cancer (NSCLC) with KRAS G12X mutations at the start and once after treatment with daraxonrasib. A complete clearance of RAS mutants was seen in 89% of patients who responded to the treatment, in 70% of patients with stable disease and in 0% of patients who progressed on treatment. The findings suggest that in advanced RAS-mutant NSCLC, response to daraxonrasib is associated with complete clearance of ctDNA for multiple RAS mutations.

Luo will share the findings of this study, titled “Early reduction in circulating tumor DNA (ctDNA) is associated with clinical activity of daraxonrasib (RMC-6236) in RAS mutant non-small cell lung cancer (NSCLC),” at the Late Breaking Research: Clinical Research 1 LB218 on Monday, April 28, 2025, from 3:00 to 6:00 p.m. ET / 2:00 to 5:00 p.m. CT.

Luo also will share early results from an ongoing phase 1 trial of a next-generation RAS inhibitor combined with a SHP2 inhibitor in patients with KRAS G12C-mutant NSCLC. This ongoing trial combines divarasib, a next-generation KRAS G12C inhibitor, with migoprotafib, a SHP2 inhibitor. In pre-clinical research, SHP2 inhibitors increased the efficacy of KRAS G12C inhibitors. In this analysis, 74 patients received the combination therapy, 48 of which had no prior KRAS G12C targeted therapy. The combination demonstrated an acceptable safety profile. Of those who had not received prior KRAS targeted therapy, the objective response rate was 43.8% and ctDNA level declines were observed, suggesting preliminary signs of clinical activity in patients with KRAS G12C-positive NSCLC.

Luo will share the findings of this study, titled “Divarasib plus migoprotafib combination treatment in patients with KRAS G12C-positive non-small cell lung cancer (NSCLC),” at the Phase 0 and Phase 1 Clinical Trials Poster Session CT022 on Monday, April 28, 2025, from 10:00 a.m. to 1:00 p.m. ET / 9:00 a.m. to 12:00 p.m. CT.

Novel targeted agent shows early signs of promise for patients with a form of gastrointestinal stromal tumor

Priscilla Merriam, MD, clinical director of the Sarcoma Center, will share results of pre-clinical research and phase 2 clinical trial results examining the potential for a novel targeted agent to treat patients with a form of gastrointestinal stromal tumor (GIST) called succinate dehydrogenase deficient GIST. This form of GIST is defined by genetic alterations that result in increased signaling through a pathway involving fibroblast growth factor receptor (FGFR). In preclinical research, the FGFR inhibitors rogaratinib and pemigatinib resulted in significant tumor suppression in patient-derived xenograft models of the disease. In the clinical trial, 24 patients with this form of GIST enrolled and received regaratinib. After a median follow-up of 17.8 months, 10 patients had a partial response and 12 had stable disease. The findings support targeting FGFR signaling in this patient group.

Merriam will share the results of the study, titled “Fibroblast growth factor receptor (FGFR) inhibition demonstrates anti-tumor activity in succinate dehydrogenase deficient gastrointestinal stromal tumor (SDHd GIST),” at the Phase II Clinical Trials 2 Poster Session CT215 on Tuesday, April 29, 2025, from 3:00 p.m. to 6:00 p.m. ET / 2:00 p.m. to 5:00 p.m. CT.

Study of combination therapy with immunotherapy for advanced salivary gland cancer suggests further investigation warranted

Glenn J. Hanna, MD, director of the Center for Salivary and Rare Head and Neck Cancers and director of the Center for Cancer Therapeutic Innovation, will share results of a phase 2 non-randomized clinical trial testing elraglusib, a glycogen synthase kinase 3 beta (GSK 3β) inhibitor plus chemotherapy with or without pembrolizumab in patients with advanced salivary gland cancers. GSK 3β can promote the growth of cancer and confer resistance to chemotherapy. Elraglusib has been shown to overcome chemotherapy resistance and to stimulate immune responses. This study aimed to determine if combining the three would be beneficial for patients with advanced salivary gland cancers, which have limited treatment options. Overall, the combination with immunotherapy was well tolerated and 18% of non-adenoid cystic carcinoma cases showed anti-tumor activity, suggesting further study of this combination is warranted in a selected population.

Hanna will share the results of the study, titled “Elraglusib, a glycogen synthase kinase 3 beta (GSK 3β) inhibitor, plus chemotherapy with or without immunotherapy for advanced salivary gland cancer,” in the Phase II Clinical Trials 2 Poster Session CT212 on Tuesday, April 29, 2025, at 3:00 to 6:00 p.m. ET / 2:00 to 5:00 p.m. CT.

Digital health coaching shows improved physical function of cancer survivors in interim analysis

Alexi Wright, MD, MPH, director of Gynecologic Oncology Outcomes Research at Dana-Farber, will share results from an interim analysis of the Comprehensive Outcomes for After Cancer Health (COACH) study, exploring a wellness intervention that aims to improve patient wellbeing and survival for patients after treatment for a range of types of cancer. The randomized, wait-list controlled study provides a six-month-long digital health coaching program to patients within one year of primary treatment or during ongoing treatment for metastatic disease. These interim results assess the physical function changes of 177 patients who have completed initial and six-month assessments. The analysis showed trending improvements from baseline to six months across all groups, regardless of race, age, cancer type and study site, except for one site that included only patients with metastatic breast cancer.

Wright will share the results of this study, titled “Comprehensive Outcomes for After Cancer Health (COACH): Interim analysis of physical function data for individuals with diverse tumor types following primary cancer therapy,” at the Survivorship Research and Supportive Care Poster Session on Sunday, April 27, 2025, from 3:00 to 6:00 p.m. ET / 2:00 to 5:00 p.m. CT.

View the full list of Dana-Farber-led research at AACR.

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