Jonathan Chatzkel, MD, assistant professor of Medicine, the Division of Hematology and Oncology, the University of Florida College of Medicine, University of Florida Health, discusses the rationale for the phase Ib/II IMMCO-1 trial (NCT05000294) investigating the combination of atezolizumab (Tecentriq) plus tivozanib (Fotivda) in metastatic castration-resistant prostate cancer (mCRPC) and other immunologically cold tumors.

The phase Ib/II study is actively enrolling patients toward an upcoming preplanned interim analysis, and investigators noted in a trial-in-progress presentation at the 2023 Genitourinary Cancers Symposium that no unexpected toxicities have been observed thus far.

The increasing use of immune checkpoint inhibitors has revolutionized cancer care, Chatzkel begins. However, some cancers are defined as immunologically hot and allow T-cell infiltration, and immunologically cold tumors do not have high T-cell infiltration, Chatzkel explains. Traditionally, immunotherapy has been heavily utilized in hot tumors, and immune checkpoint inhibitors have demonstrated limited efficacy in tumors classified as cold, including those in pancreatic cancer, prostate cancer, non–triple-negative breast cancer, non–microsatellite instability–high colorectal cancer, well-differentiated neuroendocrine cancer, and ovarian cancer. Cold tumors are believed to scarcely express PD-L1 and have a low tumor mutational burden, Chatzkel notes.

PD-1 is a coinhibitory receptor expressed on activated T cells, B cells, and natural killer cells, Chatzkel continues. Moreover, VEGF is secreted by tumors and leads to endothelial cell proliferation, vascular permeability, and vasodilation. This, in turn, leads to the development of an abnormal vasculature with excessive permeability and poor blood flow, which limits immune surveillance, Chatzkel explains.

VEGF also inhibits dendritic cell differentiation by limiting the presentation of tumor antigens to CD4 and CD8 T-cells, Chatzkel emphasizes. Therefore, investigators hypothesize that VEGF inhibition can increase the effect of immune checkpoint inhibitors in cold tumors through vascular normalization and decreasing inhibitory immune signals, Chatzkel concludes.

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Jonathan Chatzkel, MD, discusses the rationale for the phase Ib/II IMMCO-1 trial investigating the combination of atezolizumab plus tivozanib in metastatic castration-resistant prostate cancer and other immunologically cold tumors.

Dr. Chatzkel on the Rationale for the IMMCO-1 trial in mCRPC and Other Immunologically Cold Tumors

Jonathan A. Chatzkel, MD, assistant professor of medicine, Division of Hematology and Oncology, University of Florida College of Medicine, University of Florida Health, discusses the future treatment options in bladder cancer.

Maintenance immunotherapies have carved out a role in the bladder cancer treatment paradigm, Chatzkel says. The utilization of nivolumab (Opdivo) in the maintenance setting has provided a boost to overall survival, giving patients a benefit from this therapy, Chatzkel explains. Furthermore, enfortumab vedotin- ejfv (Padcev) and other antibody drug conjugates have provided other options in later-line settings, Chatzkel adds.

Therapies such as enfortumab vedotin, sacituzumab govitecan-hziy (Trodelvy), or erdafitinib (Balversa) could shift into frontline settings as patients continue to benefit and researchers learn more about the efficacy of these agents, Chatzkel concludes.

Jonathan A. Chatzkel, MD, discusses the future treatment options in bladder cancer.


 Dr. Chatzkel on Future Treatment Options in Bladder Cancer

Jonathan A. Chatzkel, MD, assistant professor of medicine, Division of Hematology and Oncology, University of Florida College of Medicine, University of Florida Health, discusses the emergence of novel therapies in relapsed/refractory locally advanced or metastatic urothelial cancer.

Novel therapies, including the antibody-drug conjugate (ADC) enfortumab vedotin-ejfv (Padcev), the ADC sacituzumab govitecan-hziy (Trodelvy), and the FGFR inhibitor erdafitinib (Balversa), have been welcome additions to the treatment of patients with metastatic urothelial carcinoma. 

Enfortumab vedotin was initially granted accelerated approval by the FDA for use in patients with locally advanced or metastatic urothelial cancer who progressed on a PD-1/PD-L1 inhibitor and a platinum-containing chemotherapy in the neoadjuvant, adjuvant, locally advanced, or metastatic settings. The accelerated approval was based on data from the phase 2 EV-201 trial (NCT03219333), which showed a 44% overall response rate with the agent. On July 9, 2021, the FDA granted a regular approval to the ADC based on confirmatory data from the phase 3 EV-301 trial (NCT03474107) and expanded the agent’s indication to include adult patients with locally advanced or metastatic urothelial cancer who are ineligible for cisplatin-containing chemotherapy and who have received 1 or more prior lines of therapy. 

Historically, treatment options were limited for patients with locally advanced or metastatic urothelial cancer who progressed on chemotherapy and immunotherapy, so the integration of these agents into the armamentarium has generated excitement in the field, Chatzkel concludes.

Jonathan A. Chatzkel, MD, discusses the emergence of novel therapies in relapsed/refractory locally advanced or metastatic urothelial cancer.  



Jonathan A. Chatzkel, MD

Articles

Dr. Chatzkel on the Rationale for the IMMCO-1 trial in mCRPC and Other Immunologically Cold Tumors

Dr. Chatzkel on Future Treatment Options in Bladder Cancer

Dr. Chatzkel on the Emergence of Novel Therapies in Metastatic Urothelial Cancer