ADCs, Cellular Therapies May Improve Outcomes in Refractory/Resistant RCC

Early phase trials investigating cellular therapies, bispecific antibodies, and antibody-drug conjugates for refractory kidney cancer may uncover strategies to overcome resistance mechanisms.

During the 2023 Genitourinary Cancers Symposium, CancerNetwork® interviewed Tian Zhang, MD, MHS, an associate professor in the Department of Medicine at Harold C. Simmons Comprehensive Cancer Center of the University of Texas Southwestern Medical Center, regarding methods to potentially improve immuno-responsiveness and decrease toxicity in patients with refractory kidney cancer who are resistant to previous treatment with immunotherapy.

Zhang discussed the importance of individually assessing patients to determine previous treatments and which therapies they are resistant to. From there, it is possible to sequence various VEGF inhibitor and immunotherapy combination regimens that could benefit the patient.

Additionally, she indicated that strategies including cellular therapies, bispecifics, and antibody-drug conjugates, although still being assessed in early phase studies, may improve safety and responses in this population.


Certainly, refractory disease and treatment selection does depend on frontline treatments and timing of resistance. Patients should be assessed individually as to how they’ve incurred their resistance and what prior therapies they’ve had. Sequencing different VEGF-targeted therapies or immunotherapy combinations in the refractory setting is an important consideration.

Generally, ipilimumab [Yervoy] does not seem to be so effective in patients who have had prior nivolumab [Opdivo], so that is a less effective strategy. Ongoing phase 3 studies like the phase 3 CONTACT-03 study [NCT04338269], phase 3 TiNivo-2 study [NCT04987203], and phase 3 PDIGREE study [NCT03793166] will also help us think about sequential treatments for metastatic renal cell carcinoma and form a novel therapy perspective.

These early phase trials with cellular therapies, bispecifics, and antibody-drug conjugates are all great ways that we can think about novel treatments in the refractory setting and efforts to both control toxicity and also improve immuno-responsiveness for kidney cancer.

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