The results of the study are particularly encouraging given the high unmet need for patients with non–clear cell renal cell carcinoma, according to lead investigator Laurence Albiges, MD, PhD.
The combination of pembrolizumab (Keytruda) and lenvatinib (Lenvima) showed encouraging antitumor activity as a frontline treatment for patients with non–clear cell renal cell carcinoma (nccRCC), according to preliminary findings from the phase 2 KEYNOTE-B61 trial presented at the 2022 ESMO Congress.1
At a median follow-up of 8.2 months (range, 5.5-10.5), the confirmed objective response rate (ORR) was 47.6% (95% CI, 36.4-58.9), comprising 3 complete responses (3.7%) and 36 partial responses (43.9%). The disease control rate (DCR), which also includes stable disease, was 79.3% (95% CI, 68.9-87.4). Progressive disease occurred in 11% of patients.
The median time to response was 2.8 months (range, 2.6-5.7) and the median duration of response was not yet reached (range, 1.4+ to 7.2+ months). The 6-month overall survival and progression-free survival rates were 87.8% (95% CI, 78.5-93.2) and 72.3% (95% CI, 60.7-81.0), respectively
“Given the encouraging ORR and DCR, lenvatinib plus pembrolizumab may represent a potential frontline treatment option for nccRCC,” said lead investigator Laurence Albiges, MD, PhD, Institut Gustave Roussy, Villejuif, France.
Patients enrolled in the single-arm KEYNOTE-B61 trial (NCT04704219) have histologically confirmed nccRCC (per investigator) with locally advanced or metastatic disease and have not received any prior systemic therapy. Overall, there were 147 patients treated in the trial, and treatment remains ongoing for 123 patients, including all patients who have achieved a confirmed response.
Efficacy was evaluated in the 82 patients who had enrolled on the trial at least 6 months prior to the data cutoff date of January 31, 2022. The RCC histology for these patients was as follows: papillary (51), chromophobe (15), unclassified (7), translocation (5), and “other” (4).
In the 82-patient efficacy population, the median age was 64 years, (range, 24-87) and 70.7% o f patients were male. The IMDC risk categories were favorable for 39% of patients and intermediate/poor for 61% of patients. Twelve percent of patients had sarcomatoid features. About two-thirds of patients had positive PD-L1 status as determined by a combined positive score ≥1. Regarding metastases, 17.1% of patients had liver metastases and 29.3% had bone metastases.
Pembrolizumab was administered intravenously at 400 mg every 6 weeks for a maximum of 18 cycles (about 2 years). Lenvatinib was administered orally at 20 mg daily. The primary end point was ORR.
In addition to assessing the study population as a whole, the investigators also determined ORR and DCR across the various histologic subgroups. The ORR and DCR were 52.9% and 78.4% in the papillary group; 13.3% and 73.3% in the chromophobe group; 71.4% and 100.0% in the unclassified group; 60.0% and 80% in the translocation group; and 50% and 75% in the “other” group.
Responses were observed regardless of IMDC risk status, with an ORR of 56.3% in the favorable risk group and 42% in the intermediate/poor risk group.
PD-L1–positive status enriched patients response with an ORR of 54.5% in these patients vs 27.3% in PD-L1–negative patients.
The safety population included all 147 treated patients. Albiges said there were no new safety signals with the pembrolizumab/lenvatinib regimen. Overall, 86.4% of patients experienced a treatment-related adverse event (TRAE) of any grade. The most common TRAEs across all grades were hypertension (48.3%), diarrhea (25.2%), and hypothyroidism (25.2%). Grade 3/4 TRAEs were experienced by 34.7% of patients and there were no patient deaths related to TRAEs.
Albiges said the results of the study are particularly encouraging given the high unmet need in nccRCC, with response rates to single-agent tyrosine kinase inhibitor therapy being “somewhere between 5% and 25% and a progression-free survival of usually less than 6 months.”
Regarding next steps for this study, she said, “Data from all patients will be presented when additional follow-up are available.”
1. Albiges L, Gurney HP, Atduev V, et al. Phase II KEYNOTE-B61 study of pembrolizumab (Pembro) + lenvatinib (Lenva) as first-line treatment for non-clear cell renal cell carcinoma (nccRCC). Ann Oncol. 2022;33(suppl_7):S660-S680. doi:10.1016/annonc/annonc1072