Oncology Experts Preview Abstracts to Watch at the 2025 AACR Annual Meeting

Ahead of the 2025 AACR Annual Meeting, OncLive® asked oncology experts across a range of specialties to share their insights on key research and presentations they are most excited to see.

We gathered exclusive perspectives from:

• Kristianna M. Fredenburg, MD, PhD, an anatomic and clinical pathologist in the Department of Pathology, Immunology, and Laboratory Medicine at the University of Florida in Gainesville
• James J. Harding, MD, an associate attending physician at Memorial Sloan Kettering Cancer Center in New York, New York
• Jia Luo, MD, a physician at Dana-Farber Cancer Institute and an instructor in medicine at Harvard Medical School in Boston, Massachusetts
• Jason Abdou Mouabbi, MD, an assistant professor in the Department of Breast Medical Oncology and the Department of General Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston
• Ravindra Uppaluri, MD, PhD, director of Head and Neck Surgical Oncology at the Brigham and Women’s Hospital and Dana-Farber Cancer Institute, as well as an associate professor of surgery at Harvard Medical School

“A focus of AACR this year will certainly be the use of antibody-drug conjugate [ADC] technologies across solid tumors,” Harding said about the meeting. “We’ll see continued bispecific [antibody] development, as well as T-cell–targeted therapies and other trials in progress.”

Here are the abstracts that made these experts’ lists:

Jason Abdou Mouabbi, MD

Breast Cancer

4613 / 3 - Differential TROP2 immunohistochemical expression between pleomorphic and classic invasive lobular carcinoma of the breast

Poster session time: Tuesday, April 29, 9:00am-12:00pm CT

Mouabbi: TROP-2 expression is important because we have targeted therapies for that protein that is expressed at the surface of cancer cells. The 2 main therapies we talk about are sacituzumab govitecan-hziy [Trodelvy] and datopotamab deruxtecan-dlnk [Datroway], which are ADCs that target TROP-2. Because of that, it’s important to characterize hormone receptor–positive, HER2-negative cancers in terms of their expression of TROP-2 to know whether those drugs will be effective or less effective in those cancers. We don’t have much data about [these agents in] lobular [disease] because it is an understudied subtype of breast cancer.

This abstract is going to shed light about TROP-2 expression in the 2 most common subtypes of lobular breast cancer: classic lobular and pleomorphic lobular. It’s important to look at the expression of TROP-2. Is it the same in both [subtypes]? [Is it] higher in one? That’s going to be hypothesis-generating for future studies.

CT235 / 4 - REPLOT Trial: Phase II study of repotrectinib with or without fulvestrant in patients with HR+ HER2- metastatic invasive lobular carcinoma previously treated with endocrine therapy and CDK4/6 inhibition

Poster session time: Tuesday, April 29, 2:00-5:00pm CT

Mouabbi: This is an exciting study because this is the first United States–based study to target this specific subtype of breast cancer called invasive lobular carcinoma. We are super excited about it. The preclinical data using [repotrectinib (Augtyro)] in that subtype of breast cancer are strong, and this study shows its activity in patients with metastatic invasive lobular carcinoma. The poster is going to be a trial in progress showcasing the study design, what we are looking for, and to increase awareness about that study in case there are physicians who have patients with invasive lobular carcinoma looking for studies or patients who are looking for those studies. The study opened for accrual in October [2024], and we’re excited about it being available for patients.

Ravindra Uppaluri, MD, PhD

Head and Neck Cancer

CT001 - 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

Session time: Sunday, April 27, 1:00-3:00pm CT

Uppaluri: KEYNOTE-689 [NCT03765918] randomly assigned over 700 patients with resectable head and neck cancers to receive standard-of-care [SOC] therapy [with or without] pembrolizumab [Keytruda] integrated as neoadjuvant and adjuvant therapy. This study [will highlight whether] neoadjuvant pembrolizumab followed by surgery and adjuvant pembrolizumab concurrent with the SOC adjuvant treatment represents a new SOC in the treatment of these patients with resectable, locally advanced head and neck cancers.

James J. Harding, MD

Hepatocellular Carcinoma (HCC)

Harding: As we come to AACR, areas that will be of great interest for HCC will be continued preclinical development of adoptive cellular therapies and T-cell receptor therapies. GPC3 is a known target, and there are many attempts at targeting this using cellular therapeutics. We’ll see continued development of bispecific and trispecific [antibodies] that are designed to activate both an immune response against HCC, as well as target antivascular signals. Finally, we’ll hear about how these technologies might be applied at earlier stages of disease, as well as biomarkers that might select out for response to treatment. AACR 2025 should be an exciting meeting for hepatobiliary cancers, as well as solid tumors as a whole.

Jia Luo, MD

Lung Cancer

CT266 - D3S-001, a next generation GDP-bound KRAS G12C inhibitor, as monotherapy in KRAS G12C inhibitor resistant non-small cell lung cancer

Session time: Tuesday, April 29, 2:30-4:40pm CT

Luo: First-generation, state-selective KRAS G12C(OFF) inhibitors have shown moderate clinical benefit in patients with KRAS G12C–mutated non–small cell lung cancer [NSCLC]. This next-generation KRAS G12C(OFF) inhibitor with faster target engagement shows promising preclinical and initial clinical activity in NSCLC. This will be an interesting presentation to learn about its activity in patients who received prior KRAS G12C(OFF) inhibitors.

Solid Tumors

462 / 23 - TNG456 is a next-generation, brain-penetrant, MTA-cooperative PRMT5 inhibitor for the treatment of solid tumors with MTAP loss

Poster session time: Sunday, April 27, 2:00-5:00pm CT

Luo: The MTAP gene is co-deleted with CDKN2A/CDKN2B in [approximately] 10% to 30% of solid tumors. Many advanced solid tumors—including NSCLC—often have central nervous system [CNS] metastasis, and many targeted therapies do not have significant CNS penetrance. A specific type of MTAP pathway inhibitor—MTA-cooperative PRMT5 inhibitors—have shown promising early phase clinical trial activity. [TNG456] is a promising CNS-penetrant, MTA-cooperative PRMT5 inhibitor entering clinical trials.

Kristianna M. Fredenburg, MD, PhD

1229 / 13 - 3D-bioprinted cancer models for prediction of drug response driven by H&E-based AI algorithm.

Poster session time: Monday, April 29, 9:00am-12:00pm

Fredenburg: This poster describes a highly innovative 3-dimensional [3D]–bioprinted cancer model that uses patient-derived tumor cells along with a tumor microenvironment generated from the patient’s peripheral blood mononuclear cells. Distinctively, they utilize a deep learning approach to predict gene expression from H&E slides, generating a treatment response score that guides the selection of investigational therapies to test within the 3D model. The authors then provide real-world results as they describe a change in a melanoma patient’s survival outcomes via predicted drug response corrobated by their 3D model. This poster is exciting to me as a pathologist because it highlights how digital pathology and artificial intelligence are being used to push the creative boundaries of precision medicine.

CT109 / 4 - A first-in-human phase 1 study of LY4050784, an oral, potent, and selective SMARCA2 inhibitor, in patients with advanced solid tumors with SMARCA4 alterations (Trial in Progress)

Poster session time: Monday, April 28, 2:00-5:00pm CT

Luo: There are no approved targeted therapies for SMARCA4 altered cancers, which are often aggressive and difficult to treat. [LY4050784] is an oral targeted therapy that takes advantage of the fact that SMARCA4-deficient cancers are dependent on SMARCA2 activity. This will be an interesting report of a trial in progress testing a promising targeted therapy for SMARCA4-altered cancers.