The Targeted Pulse: New Immunotherapy, Antibody-Drug Conjugate, and NMT Inhibitor on the Horizon

A New Immunotherapy Approach to Cancel Chemotherapy Once and For All

What if oncologists could retrain the immune system to recognize and control or eliminate a possible cancer, with ongoing ability to surveil and prevent recurrence? Mark Dybul, MD, introduces a new immunotherapeutic approach that enhances immune stimulation with dendritic cells from another human.

Dybul–chief executive officer of Renovaro Biosciences, professor in the Department of Medicine at Georgetown University, and senior advisor at the Center for Global Health Practice and Impact–stated that this is a key to treating difficult-to-treat tumors, such as pancreatic and triple-negative breast cancer. “[Renovaro’s] mission is to create a future free from toxic chemotherapy using [this method]. We believe it is very possible, and our preliminary data suggest that is the case.”

Trastuzumab Nears the Finish Line for HER2+ Solid Tumors

The first tumor-agnostic HER2-directed therapy and antibody-drug conjugate, trastuzumab deruxtecan (T-Dxd; Enhertu), is making regulatory headway for the treatment of unresectable or metastatic HER2-positive solid tumors, receiving priority review by the FDA based on findings of the DESTINY-PanTumor02 study (NCT04482309).

“Biomarkers for HER2 expression are already established in breast and gastric cancers, but we must now define them across tumor types,” said Susan Galbraith, executive vice president of oncology research and development at AstraZeneca, in a news release. She pledged to work alongside the FDA “to bring this …to patients as quickly as possible.”

Early Data Show Promise of Zelenirstat for Advanced Cancers

Zelenirstat (PCLX-001) is a new neuromuscular therapy that has shown promising results in a phase 1 study. The study evaluated 29 heavily pretreated patients with solid tumors or lymphomas, all of whom had relapsed/refractory disease and received an average of 4 prior lines of therapy. Specifically, 8 patients had colorectal cancer, 2 had pancreatic cancer, and 1 had appendiceal cancer.

“This is a new mechanism of action we are targeting… As far as I am aware, this is the first trial being done in this class of compound,” Randeep Sangha, MD, medical oncologist at the Cross Cancer Institute, said in an interview with Targeted OncologyTM.

High-Dose Radiation, Long-term ADT Extends Outcomes in High-Risk Prostate Cancer

After a 10-year follow-up, patients with high-risk prostate cancer treated with a higher dose of radiation therapy along with long-term androgen deprivation therapy (ADT) experienced extended survival outcomes. This included progression-free survival (PFS), cancer-specific survival, and overall survival, according to data from the GETUG-AFU 18 trial (NCT00967863).

Without increasing toxicity and showing no difference in quality of life, “…we have now level 1 evidence that high-dose [radiotherapy] with long-term ADT must be the standard of care in high-risk prostate cancer patients,” Christophe Hennequin, MD, PhD, Department of Radiation Oncology, Saint-Louis Hospital, Paris, said during a presentation of the data at the 2024 Genitourinary Cancers Symposium.

Cabozantinib Combination Extends PFS Vs Novel Hormonal Therapy in Metastatic CRPC

The cabozantinib (Cabometyx) and atezolizumab (Tecentriq) combination came out ahead second-line novel hormonal therapy (NHT), with significantly higher PFS rates for patients with metastatic castration-resistant prostate cancer (CRPC), according to the phase 3 CONTACT-02 trial (NCT04446117). The PFS benefit with the cabozantinib-based regimen extended across most subgroups.

“These data support [cabozantinib plus atezolizumab] as a potential new treatment option for patients with [metastatic] CRPC who have progressed on an NHT,” author Neeraj Agarwal, MD, a professor of medicine, presidential endowed chair of cancer research, and director of both the Genitourinary Oncology Program and the Center of Investigational Therapeutics at the Huntsman Cancer Institute of the University of Utah, said.

Thank you for joining us for this week’s Targeted Pulse. Look out for more recaps to come.