Staying Current: Your Guide to August 2025 Oncology Research

Check out our most viewed stories including women in breast surgical oncology, novel cancer vaccines in gastrointestinal cancer, and the FDA approval of dordaviprone (Modeyso).

The CancerNetwork® Five Above the Fold is here for quick recaps on the hottest oncology news from August. Check out our most viewed stories including women in breast surgical oncology, novel cancer vaccines in gastrointestinal cancer, and the FDA approval of dordaviprone (Modeyso).

#1: Reshaping Breast Cancer Surgery and Minimizing Radical Treatment Approaches

Tran Ho, DO, FSSO, FACS, a breast surgical oncologist at El Camino Health, highlighted the evolution of breast cancer surgery from radical procedures to less invasive, personalized approaches. At El Camino Health in particular, she is establishing a multidisciplinary breast cancer clinic to provide comprehensive and personalized care, which will improve patient outcomes through collaborative decision-making.

Ho also participated in the PREDICT Registry study (NCT03448926), which evaluated DCISionRT to predict the benefits of radiation therapy in patients with ductal carcinoma in situ. Updated data from the study revealed that the tool changed recommended radiation therapy regimens for a large percentage of patients, helping to avoid both under- and overtreatment. Ho noted that the primary goal in the breast cancer field is ideally to achieve better efficacy outcomes with fewer adverse effects, as evidenced by the shift toward more breast-conserving surgeries and advancements like sentinel lymph node surgery, which has reduced complications like lymphedema.

#2: Novel Vaccine Shows Early Responses in Pancreatic Cancer and CRC

Data from the phase 1 AMPLIFY-201 trial (NCT04853017) of ELI-002 2P, a novel vaccine for patients with pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC) with KRAS mutations showed that the vaccine produced immune responses, including potent CD4-positive and CD8-positive T-cells, which may correlate with delayed tumor recurrence. The vaccine is an off-the-shelf amphiphile lymph node–targeted immunotherapy.

Data from the trial showed that 84% of patients had a KRAS mutation-specific T-cell response, and these responses correlated with overall tumor biomarker response. The median overall survival was 28.94 months, and the median radiographic relapse-free survival was 15.31 months. The study’s authors believed that the long-term follow-up data support continued research of this immunotherapy, and a randomized phase 2 study with a different formulation of ELI-002 was initiated. The broad availability of the vaccine supports its continued development for numerous KRAS mutation-expressing tumor types.

#3: Tarlatamab and DLL3 May Open New Opportunities in SCLC Management

DLL3, an actionable biomarker for cellular therapy agents such as tarlatamab-dlle (Imdelltra), may provide new opportunities in the management of small cell lung cancer (SCLC), a disease that has seen few treatment advancements. Daniel R. Carrizosa, MD, MS, FACP, highlighted findings across multiple studies at the 2025 National Immune Cell Effector Therapy (ICE-T) Conference, noting that SCLC’s propensity for early metastasis and high recurrence rates contribute to a 5-year survival rate of 3.6% for patients with extensive-stage SCLC.

Where previous attempts to target DLL3 with another therapy have failed, tarlatamab, a bispecific T-cell engager, has shown promise in multiple clinical trials. Data from studies such as the phase 2 DeLLphi-301 trial (NCT05060016) and phase 3 DeLLphi-304 trial (NCT05740566) demonstrated promising outcomes, including improved overall survival (OS). Specifically, tarlatamab displayed a median OS of 13.6 months vs 8.3 months with chemotherapy (HR, 0.60; 95% CI, 11.1-NE; P < .001). Common adverse effects associated with tarlatamab included cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, and logistical challenges emerged.

The path forward, according to Carrizosa, involved ongoing clinical trials for tarlatamab and other emergent DLL3-targeting therapies.

#4: Enfortumab Vedotin/Pembrolizumab Improves Survival vs Surgery in MIBC

The phase 3 EV-303/KEYNOTE-905 trial (NCT03924895), which evaluated enfortumab vedotin (Padcev) and pembrolizumab (Keytruda) in patients with muscle-invasive bladder cancer (MIBC) who were ineligible for or have declined cisplatin-based chemotherapy, found that the combination led to a significant improvement in event-free survival and overall survival when used before and after surgery, compared with surgery alone. Furthermore, this combination was the first therapy to demonstrate a significant survival benefit for this patient population, who previously had limited options beyond surgery and faced a high risk of disease recurrence.

The safety profile of the combination therapy was consistent with previously known data for each drug. The results, according to the developers, will be submitted to global health authorities for regulatory approval. Additionally, this combination, which is approved as a therapy for patients with locally advanced or metastatic urothelial cancer regardless of cisplatin eligibility in the US, EU, and several countries, is under evaluation in patients with cisplatin-eligible MIBC in the phase 3 EV-304/KEYNOTE-B15 trial (NCT04700124) in the neoadjuvant and adjuvant settings.

#5: FDA Grants Accelerated Approval to Dordaviprone in Diffuse Midline Glioma

In August 2025, the FDA granted accelerated approval to the protease activator dordaviprone (Modeyso) for adult and pediatric patients 1 year or older with H3 K27M-mutated diffuse midline glioma that has progressed following prior therapy. Dordaviprone is the first systemic therapy approved for this patient population. The approval was based on data from 5 open-label trials, which demonstrated an overall response rate of 22% in an integrated efficacy population of 50 evaluable patients. The median duration of response was 10.3 months, with 73% of responders maintaining a response for at least 6 months.

The recommended dose for adults is 625 mg orally once a week, with pediatric dosing dependent on weight. Warning and precautions in the prescribing information include hypersensitivity, QTc interval prolongation, and embryo-fetal toxicity. Common adverse effects included fatigue and headache, and in pediatric patients, nausea and vomiting. Routine blood monitoring is also recommended due to a potential decrease in lymphocyte count. The approval follows a decision from the FDA, which granted priority review to dordaviprone as a treatment for this patient population in February 2025.