Dr Qin on Upcoming Areas of Interest in RCC Research

Qian (Janie) Qin, MD, assistant professor, Division of Hematology and Oncology, Department of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses upcoming areas of interest in the renal cell carcinoma (RCC) armamentarium.

An extensive area of research focus will revolve around identifying biomarkers indicative of response to treatments such as VEGF TKIs and immunooncology (IO) agents, Qin begins. Despite the availability of several first-line treatment options for patients with RCC, there is still uncertainty regarding which patients truly benefit from IO/IO combinations as opposed to IO/TKI combinations, Qin explains. Any biomarkers aiding in this distinction would be immensely valuable, she notes. Additionally, Qin says that the genuine role of triplet therapy in the upfront setting remains unclear. Unfortunately, the phase 3 COSMIC-313 trial (NCT03937219) data did not align with hypothesized expectations, with a significant number of patients experiencing toxicities and challenges in achieving the full therapeutic dose. 

Although efforts are underway to develop novel triplet therapies for patients with RCC, elucidating the role of treatment escalation with triplet therapy is crucial for patients with advanced disease, she states. In the context of localized tumor treatment, the deficiency of biomarkers persists, Qin expands. Determining which patients truly benefit from perioperative treatment, especially in the adjuvant setting, remains a challenge, she emphasizes. Measuring levels of circulating tumor DNA or other biomarkers mayexceed the scope of Tumor Node Metastasis staging and tumor grade to identify patients who may benefit from certain therapies in the localized setting, she elucidates.

Qin continues by saying she is interested in biomarker discovery and innovative therapeutic combinations. At UT Southwestern, Qin says that the kidney cancer team is actively involved in developing novel radiotracers as biomarkers for kidney cancer response. For example, an ongoing initiative will examine a HIF-2α inhibitor, serving as a precursor for a novel radiotracer to gauge response to HIF-2α inhibition. A study with this radiotracer is also in progress and holds promise for advancing the RCC field’s understanding of therapeutic responses, she concludes.

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Qian (Janie) Qin, MD, discusses upcoming areas of interest in the renal cell carcinoma armamentarium.


Qian (Janie) Qin, MD, assistant professor, Division of Hematology and Oncology, Department of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses the investigation and use of CAR T-cell therapy in patients with advanced clear cell renal cell carcinoma (ccRCC).

In the field of hematology, CAR T-cell therapy has brought about a profound transformation in the landscape of treatment, yielding remarkable responses, Qin begins. Nevertheless, when it comes to the context of solid tumors, a distinctive array of challenges emerges in the utilization of CAR T-cell therapy, Qin highlights, as T cells are genetically engineered to seek out tumor-associated antigens. An essential requirement of CAR T-cell therapy efficacy is the establishment of a nonclassical immune synapse between CAR T cells and their intended target, she notes. This interaction enables CAR T cells to recognize the presence of tumor cells and subsequently initiate cytotoxic activities, she explains. In the case of solid tumors, however, CAR T cells must overcome a sequence of obstacles, Qin emphasizes.

Initially, CAR T-cells must navigate their way to the tumor site, a journey often involving the traversal of multiple layers of extracellular matrix, Qin expands. Once this is accomplished, they may encounter a hostile tumor microenvironment, she adds. The journey of CAR T-cell therapy to specific regions within the tumor is characterized by a series of challenges and intricate steps, Qin emphasizes.

Another set of challenges revolves around the identification of tumor-associated antigens, she continues. The most favorable tumor-associated antigens are those that exhibit consistent and high levels of expression in tumor cells while remaining absent in normal cells, Qin explains. The presence of these antigens in normal cells could lead to significant autoimmune adverse effects, she says. The process of pinpointing the appropriate tumor-associated antigen for CAR T-cell therapy is of utmost importance, although it may pose a formidable challenge, Qin concludes.

Qian (Janie) Qin, MD, discusses the investigation and use of CAR T-cell therapy in patients with advanced clear cell renal cell carcinoma.


Dr Qin on the Use of CAR T-Cell Therapy in ccRCC

Qian (Janie) Qin, MD, assistant professor, Division of Hematology and Oncology, Department of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses emerging treatment regimens for patients with advanced clear cell renal cell carcinoma (ccRCC).

In the field of advanced ccRCC, emerging treatment approaches have shifted toward combination therapies, Qin begins. These combinations encompass either dual immunotherapy regimens, such as the notable ipilimumab (Yervoy) and nivolumab (Opdivo) doublet pairing, or an immunotherapy agent combined with a VEGF TKI, Qin explains.

When considering treatment with immunotherapy combined with a VEGF TKI, there are 4 prominent choices within the current treatment landscape, Qin expands. Three of these regimens, pembrolizumab (Keytruda) combined with axitinib (Inlyta), nivolumab combined with cabozantinib (Cabometyx), and pembrolizumab combined with lenvatinib (Lenvima), are all approaches that are typically preferred by oncologists, given that the survival data with the fourth combination, avelumab (Bavencio) combined with axitinib, are not yet sufficiently mature, Qin emphasizes. Despite the considerable improvement in response rates achieved with these therapies, further progress is needed to induce more complete responses and improve response rates for patients, Qin notes.

Promising treatment alternatives have emerged for patients with advanced or metastatic RCC, Qin continues, citing that triplet therapy approaches targeting the HIF pathway have been introduced. In addition, novel immunotherapies and VEGF TKIs are in the developmental pipeline, she adds. Within the realm of kidney cancer treatment are innovative therapies featuring unique mechanisms of action, such as the phase 3 COSMIC-313 trial (NCT03937219) regimen. Other ongoing trials are exploring various triplet therapy combinations alongside the investigation of the HIF2α inhibitor belzutifan (Welireg) and potential treatments related to the HIF2 pathway, such as ARO-HIF2, that target resistance to HIF2-directed drugs, Qin notes. Furthermore, ongoing evaluations of emerging single-agent, double-agent, and triplet therapies are incorporating belzutifan, she says. Novel mechanisms are also being explored, encompassing CAR T-cell therapy and radioligand therapy, Qin concludes.

Qian (Janie) Qin, MD, discusses emerging treatment regimens for patients with advanced clear cell renal cell carcinoma. 


Dr Qin on Emerging Treatment Options in ccRCC

Qian (Janie) Qin, MD, assistant professor, Division of Hematology and Oncology, Department of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses several belzutifan (Welireg) combination strategies under investigation in advanced clear cell renal cell carcinoma (ccRCC).

Current research has demonstrated that HIF2α inhibition appears to be well tolerated when given as a monotherapy in RCC, Qin begins. Accordingly, there is substantial interest in exploring the agents efficacy in combination with other standard agents in this space, Qin states. For example, the first-in-class, small molecule HIF2α inhibitor belzutifan is currently being investigated in several clinical trials alongside VEGF TKIs. 

In the phase 2 LITESPARK-003 trial (NCT03634540), belzutifan was evaluated in combination with cabozantinib (Cabometyx) for patients with advanced ccRCC who had been previously exposed to immunotherapy. Patients received a daily 120 mg dose of belzutifan and 60 mg dose of cabozantinib (Cabometyx) in 2 cohorts of patients. Cohort 1 consisted of treatment-naïve patients, and cohort 2 was comprised of patients who had received up to 2 prior lines of systemic therapy and immune checkpoint inhibitors.

Preliminary efficacy results showed that the combination generated promising antitumor activity and manageable safety in both populations, producing a confirmed overall response rate (ORR) of 57% in cohort 1. An updated analysis of cohort 2 revealed that the combination elicited an ORR of 30.8% and a disease control rate of 92% after approximately 2 years of follow up.

These results support further study of VEGF TKI and HIF-2 inhibitor combinations in RCC. One such study is the phase 3 LITESPARK-011 trial (NCT04586231), which will investigate the combination of belzutifan and lenvatinib (Lenvima) vs cabozantinib alone in patients with advanced RCC who experienced disease progression after prior anti-PD-1/PD-L1 therapy in the first- or second-line setting or as adjuvant therapy.

Qian (Janie) Qin, MD, discusses several belzutifan combination strategies under investigation in advanced clear cell renal cell carcinoma.

Qian (Janie) Qin, MD

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Dr Qin on Upcoming Areas of Interest in RCC Research

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