Kidney Cancer (RCC) Clinical Trials

About Kidney Cancer (RCC) trials

RCC trials test for a small set of biomarkers because most kidney cancer trial eligibility depends on histology and treatment history more than on molecular profile. Trials test for VHL, PBRM1, PD-L1 (CD274), and MET. VHL mutations are present in the large majority of clear cell RCC tumors and are tested both somatically (in the tumor) and in germline form (for VHL syndrome screening). PBRM1 mutations occur in roughly 40% of clear cell RCC and are studied as a potential immunotherapy response marker. PD-L1 status gates a small subset of IO trials, though kidney cancer immunotherapy is typically used regardless of PD-L1 expression. MET alterations are most relevant in papillary RCC (especially type 1), where they drive a distinct trial set. Histology subtype itself (clear cell vs papillary vs chromophobe vs other non-clear cell variants) determines which trials apply more than any individual molecular marker does.

Trials in RCC have been transformed by combination immunotherapy regimens, and most current activity sits around extending and refining those regimens. Front-line metastatic clear cell trials test new combinations of IO with IO or IO with VEGF/TKI agents. Adjuvant trials enroll patients after nephrectomy for high-risk disease, testing IO monotherapy and IO combinations. Second-line and later trials are an active space because patients post first-line IO + TKI have multiple paths forward but no clear standard, with novel TKIs, IO rechallenge regimens, and combinations all in trial. HIF2α inhibitor trials are growing, with belzutifan approved for advanced RCC after prior PD-1/PD-L1 inhibitor and VEGF-TKI therapy as well as for VHL syndrome-associated tumors, driving trials into earlier lines and combinations. Non-clear-cell RCC has its own trial set, often as separate cohorts within larger studies, focused on histology-specific biology (papillary RCC trials around MET, chromophobe trials around metabolic targets). Cytoreductive nephrectomy trials examine when surgery should be sequenced relative to systemic therapy.

RCC trial screening typically checks histology, prior systemic therapy, and IMDC risk classification. Histology confirmation: most metastatic trials are either clear cell only, non-clear cell only, or stratified by subtype. Prior IO and TKI exposure is the biggest gating factor for second-line and later trials, with most trials specifying which agents the patient has received and in what sequence. IMDC risk category (favorable, intermediate, or poor) appears in many trial inclusion or stratification criteria, especially front-line trials. Sarcomatoid or rhabdoid features in the tumor sometimes qualify or exclude patients depending on the trial. Brain metastasis status, where many trials require treated and stable disease. ECOG of 0 or 1 is standard. For adjuvant trials: time since nephrectomy, pT/pN stage, and tumor grade are commonly required.

Biomarkers tested in Kidney Cancer (RCC) trials

These are the molecular markers most commonly required or evaluated in Kidney Cancer (RCC) eligibility criteria. OncoMatch extracts them from each trial's protocol and matches them against your test results.