Welireg – Promising Addition to Treatment of Renal Cell Cancer
The combination of Welireg (Belzutifan) and Lenvima (Lenvatinib) was found to be well tolerated and generated responses in patients with advanced clear cell renal cell carcinoma whose disease had progressed following treatment with PD-1/L1 immunotherapy and a tyrosine kinase inhibitor, according to preliminary results released from the early phase KEYMAKER-U03B clinical trial.1,2
Cancer Connect Kidney Cancer Newsletter
About Renal Cell Carcinoma
Each year in the United States, more than 60,000 people are diagnosed with kidney cancer. The most common type of kidney cancer is clear cell renal cell carcinoma (RCC), which starts in the lining of very small tubes (tubules) in the kidney. For people with advanced or metastatic RCC (cancer that has spread to other parts of the body), precision cancer medicines and immunotherapies can play an important role in treatment. Approximately 20-30% of patients with RCC will have metastases at diagnosis and as many as 40% will demonstrate metastasis after treatment for earlier stage RCC. With a 5-year survival rate ranging from 5-10% for patients with advanced RCC, the overall prognosis for patients was poor historically.3,4,5 Several newer precision cancer medicines and immunotherapy have improved outcomes.
About Welireg (Belzutifan-MK-6482)
Weilreg is a novel, potent and selective inhibitor of HIF-2α. Proteins known as hypoxia-inducible factors, including HIF-2α, can accumulate in patients with Von Hippel Lindau disease, a tumor-suppressor protein, is inactivated. If not properly regulated, the accumulation of HIF-2α can stimulate several oncogenes associated with cellular proliferation, angiogenesis and tumor growth, leading to the growth of both benign and malignant tumors. This inactivation of VHL has been observed in more than 90% of clear cell RCC tumors. Research into VHL biology that led to the discovery of HIF-2α was awarded the Nobel Prize in Physiology or Medicine in 2019.
Results from the KEYMAKER-U03B clinical trial showed that at a median follow-up of 6.9 months, a regimen combining Welireg with the VEGF-TKI Lenvima elicited an objective response rate of 50% among 24 patients with refractory cancer. The median duration of response was not reached with the longest response exceeding 14 months). Nearly three-fourths (74%) of responders remained in response for 12 months or longer.
Welireg received FDA approval based on results from the LITESPARK-005 (NCT0419575) clinical trial that compared it to everolimus in 746 patients with unresectable locally advanced or metastatic clear cell renal cell carcinoma that had progressed following treatment with both a PD-1 or PD-L1 checkpoint inhibitor and a VEGF-TKI. Welireg was shown to modestly delay the time to cancer recurrence.6
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The most common significant side effects from the treatment regimen were anemia, fatigue, hypertension diarrhea, nausea, decreased appetite, and protein in the urine. There were no fatal toxicities.
The combination of welireg and Lenvima is being further evaluated in the phase 3 LITESPARK-011 clinical study (NCT04586231), which is comparing the combination to Cabometyx (cabozantinib) in patients with advanced RCC and disease progression after treatment with a PDL-1 inhibitor.
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Connect With Others for Support and information
CancerConnect was the first social network created for people with renal cell cancer. Founded by oncologists to support cancer patients and their caregivers, over 40 million individuals have accessed CancerConnect programs since 1997. CancerConnect is used by leading cancer centers like Dana Farber, Roswell Park and The James at Ohio State to support their patients. Join the conversation, ask questions, share your experience, and learn how the best cancer centers are treating cancer from others. Share your experience, ask a question, or start a conversation by posting on CancerConnect.
References
- Albiges L, Beckermann K, Miller WH, et al. Belzutifan plus lenvatinib for patients (pts) with advanced clear cell renal cell carcinoma (ccRCC) after progression on a PD-1/L1 and VEGF inhibitor: Preliminary results of arm B5 of the phase 1/2 KEYMAKER-U03B study. J Clin Oncol 41, 2023 (suppl 16; abstr 4553) doi: 10.1200/JCO.2023.41.16_suppl.4553
- NIH ClinicalTrials.gov. Substudy 03B: A Study of Immune and Targeted Combination Therapies in Participants With Second Line Plus (2L+) Renal Cell Carcinoma (MK-3475-03B). Last updated May 18, 2023. Accessed June 2, 2023. https://clinicaltrials.gov/ct2/show/NCT04626518
- Ljungberg B, Campbell S and Cho H. The Epidemiology of Renal Cell Carcinoma. Eur Urol. 2011;60:615-621.
- https://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/rare-kidney-tumors/clear-cell-renal-cell-carcinoma#:~:text=How%20common%20is%20ccRCC%3F,young%20adult%20kidney%20cancer%20cases.
- Escudier B, Porta C, Schmidinger M et al Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annal Oncol. 2014; 25(Suppl3):iii49-iii56.
- https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-belzutifan-advanced-renal-cell-carcinoma?utm_medium=email&utm_source=govdelivery
