DelveInsight has covered pivotal abstracts presented in the ASCO21 revolving around Renal Cell Carcinoma. Have a read below.
Abstract #4555: MK-6482-004 trial, Belzutifan, Merck's Phase II Study: Overcoming the unmet need in VHL associated Clear Cell RCC Treatment Landscape
On the very first day of ASCO 2021, Merck presented the Phase II results of its breakthrough drug, Belzutifan (MK-6482), an oral hypoxia-inducible factor 2α (HIF-2α) inhibitor, for Von Hippel-Lindau (VHL) disease-associated clear cell renal cell carcinoma (ccRCC). The trial was analyzed in 61 patients, with a median duration of treatment of 68 weeks, and almost 56 patients (92%) remain on therapy. The drug showed a confirmed overall response rate (ORR) of 36.1%, which was the primary endpoint of the trial. In patients with confirmed PR, the median duration of response (DOR) was not reached, and 56 patients (92%) had some reduction in the sum of all target lesion diameters. Interestingly, the progression-free survival (PFS) rate at the 52nd week was 98%. Although Merck had already published a part of the result earlier, it has now published results for non-RCC tumors as well, where ORR was 80% in pancreatic neuroendocrine tumors (pNETs) and 32% in CNS hemangioblastomas. Meanwhile, only 13% of patients had a grade 3 Treatment-related adverse events (TRAE). Overall, the drug demonstrated clinical benefit and has a favorable safety profile in patients with VHL disease-associated ccRCC, pNETs, and hemangioblastomas.
Considering that preliminary phase II analysis of the HIF-2a inhibitor Belzutifan in combination with Cabozantinib has already been discussed in the recent ASCO GU 2021, there are few positive Oncologist reviews:
"HIF-2a inhibition with belzutifan has a good disease control rate (80%) and PFS (15months) in pretreated clear cell RCC. The safety profile is different from VEGF TKIs. The durability and safety data suggest this will become another weapon, especially in combination."
"Wonderful work to bring belzutifan into the equation for refractory Kidney Cancer."
Taking into account that the company has already received a Priority Review for this HIF-2α Inhibitor, they are eagerly waiting for the approval around its Prescription Drug User Fee Act (PDUFA) date in September 2021. We believe that Merck could be the first entrant to overcome the unmet need in the VHL space, whereas many as 70% of people with VHL disease develop RCC.
Abstract #4560: Phase III CLEAR Study, Merck and Eisai's Keytruda and Lenvima Combination Subgroup analysis of Clear cell RCC patients
Last month, Merck and Eisai already received the US FDA's Priority Review for Keytruda (pembrolizumab) + Lenvima (lenvatinib) Applications to treat Advanced Renal Cell Carcinoma. In the ongoing ASCO 2021, Merck presented the depth of response and efficacy for selected subgroups in the Keytruda + Lenvima and Sunitinib treatment arms. Among 1,069 patients randomized in the CLEAR study, 355 were assigned to Keytruda + Lenvima and 357 to Sunitinib. Median follow-up was 27 months for the Keytruda + Lenvima group and 26 months for the Sunitinib group. PFS favored Keytruda + Lenvima (median 22.1 months) versus Sunitinib (median 5.9 months) in the IMDC-intermediate/poor subgroup; and in the IMDC-favorable subgroup (median 28.1 months vs median 12.9 months). In fact, Overall Survival also favored Keytruda + Lenvima versus Sunitinib in the IMDC-intermediate/poor subgroup. The study concluded that in patients with target kidney lesions, Keytruda + Lenvima conferred survival benefits versus Sunitinib, similar to benefits observed in the overall population.
Vice-Chair NCCN Guideline Panel quoted, "All of these various factors, together, show that this is one of the strongest regimens that's been tested so far in this particular setting, in advanced kidney cancer. And so the NCCN panel felt that these data deserve preferred status,"
Excitingly, the combination regimen has already been recommended by NCCN for front line setting in RCC as a whole; we believe this amazing combination will further benefit clear cell RCC patients, also considering its established efficacy and analysis at a broader level now.
The Day 1 of the ASCO21 is witnessing a plethora of presentations and results of clinical trials, and DelveInsight is ready to stretch more. Catch up with us here.
