Clinical Trial Confirms Keytruda and Lenvima Benefit in Kidney Cancer

Updated results from the phase 2 KEYNOTE-B61 trial showed that combining Keytruda (pembrolizumab) with Lenvima (lenvatinib) continued to help shrink tumors and improve survival when used as a first treatment for people with advanced non-clear cell kidney cancer, according to data presented at the 2025 Kidney Cancer Research Summit.

Among all evaluable patients who received Keytruda plus Lenvima (152 patients), the overall response rate was 50.6%, the disease control rate was 82.3% and the clinical benefit rate was 71.5%. Data showed complete responses in 10.1% of patients and partial responses in 40.5%.

The study treatment yielded an overall response rate of 53.8% in patients with papillary disease (93 patients), 31% in those with chromophobe histology (29 patients) and 66.7% in those with translocations (6 patients). Additionally, 50% and 77.8% of patients with unclassified (20 patients) and other histology (9 patients) experienced a response.

Any reduction in tumor burden occurred in 88.6% of all patients. Tumor burden reductions were observed in 91.4% of those with papillary disease, 75.9% of those with chromophobe histology, 95% of those with unclassified disease, 100% of those with translocations and 88.9% of those with other histologies. The median duration of response was 23.5 months.

The median progression-free survival was 17.9 months across the overall population, which included a progression-free survival rate of 39% at 24 months and 26% at 36 months. Additionally, the median progression-free survival was 17.7 months in the papillary subgroup and 11.3 months in the chromophobe subgroup. In each respective group, the 24-month progression-free survival rate was 35% and 44%, and the 36-month rate was 22% and 27%.

Across the overall population, the study treatment produced a median overall survival of 41.5 months, with overall survival rates of 67% at 24 months and 54% at 36 months. The median overall survival was 37.5 months in the papillary subgroup and was not reached in the chromophobe subgroup. The overall survival rates in each group were 65% versus 69% at 24 months, and 50% versus 62% at 36 months.

“After a minimum of 3 years of follow-up, Keytruda plus Lenvima continued to show durable antitumor activity and promising survival outcomes in the first-line setting for patients with advanced non-clear cell renal cell carcinoma,” lead study author Dr. Laurence Albiges, stated in the presentation. “As of now, this is one of our standards of care to treat patients including papillary, chromophobe or different histologies than non-clear cell renal cell carcinoma. We're excited that this has changed the paradigm for our patients.”

Albiges is head of the Department of Oncology at Institut Gustave Roussy.

In the single-arm KEYNOTE-B61 trial, 158 patients were assigned to receive Keytruda at 400 mg intravenously every 6 weeks for a maximum of 18 cycles plus Lenvima at 20 mg orally once daily.

The trial’s primary end point was overall response rate per blinded independent central review using RECIST 1.1 criteria. Secondary end points included duration of response, progression-free survival, overall survival and safety.

Patients 18 years and older with histologically confirmed stage 4 non-clear cell renal cell carcinoma, measurable disease per RECIST 1.1 guidelines, a Karnofsky performance status of 70% or higher and no prior therapy for advanced disease were eligible for enrollment on the trial. Having adequately controlled blood pressure with or without antihypertensive medications as well as adequate organ function were additional requirements for study entry.

The median patient age was 60 years. The most common histology was papillary (58.9%) followed by chromophobe (18.4%), unclassified (12.7%), other (5.7%), translocated (3.8%) and medullary (0.6%). Additionally, 12% of patients had sarcomatoid features and 63.3% had an intermediate or poor International Metastatic Renal Cell Carcinoma Database Consortium risk.

Investigators administered any subsequent therapy to 38.6% of the study population. The most common types of subsequent treatment included any VEGF or VEGFR inhibitor (35.4%), any mTOR inhibitor (8.9%) and any PD-(L)1 inhibitor (6.3%).

Any-grade side effects affected 99.4% of patients and 77.2% experienced grade 3 to 5 toxicities. Additionally, 31% of side effects resulted in treatment discontinuation, 48.1% had serious side effects and 6.3% had side effects leading to death. Any-grade and grade 3 or higher treatment-emergent side effects affected 96.2% and 60.1% of patients, respectively, and any-grade and grade 3 or higher immune-mediated side effects occurred in 58.9% and 10.1%.

The most common treatment-emergent side effects included hypertension (57.6%), diarrhea (50%), hypothyroidism (41.1%), proteinuria (34.2%), fatigue (31%), palmar-plantar erythrodysesthesia syndrome (30.4%), dysphonia (29.1%) and diminished appetite (27.2%). Other treatment-emergent side effects included nausea (25.3%), decreased weight (22.8%), asthenia (22.2%), arthralgia (19.6%), stomatitis (19.6%), mucosal inflammation (15.2%) and pruritus (15.2%).

References

1. “Pembrolizumab plus lenvatinib for previously untreated advanced non–clear cell renal cell carcinoma: 3-year follow-up of the phase 2 KEYNOTE-B61 study,” by Dr. Laurence Albiges. Presented at the 2025 Kidney Cancer Research Summit; July 17-18, 2025; Boston, MA. Abstract 1.
2. Pembrolizumab plus lenvatinib for first-line advanced/​metastatic non-clear cell renal cell carcinoma (1L nccRCC) (MK-3475-B61) (KEYNOTE-B61). ClinicalTrials.gov. Updated February 17, 2025. Accessed July 21, 2025.

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