Lenvatinib Gets Updated Label to Include First-Line Efficacy in Advanced nccRCC

Kidneys, adrenal glands, genitourinary system, body scan, joint, medical screen 3D render, human anatomy, computer anatomy, body skeleton, X-ray scan: © Leo Viktorov - stock.adobe.com

The label for lenvatinib (Lenvima), an orally available multiple receptor tyrosine kinase inhibitor (TKI), has been updated to include efficacy data for the first-line treatment of advanced non-clear cell renal cell carcinoma (nccRCC).¹

Data from the phase 2 KEYNOTE-B61 (NCT04704219), which evaluated lenvatinib given in combination with pembrolizumab (Keytruda) for the first-line treatment of adult patients with advanced nccRCC, support this label update.

However, the approved indication for this combination as a first-line treatment of adult patients with advanced RCC is unchanged.

“[Genitourinary] oncologists and community oncologists are well aware of the strong antitumor effects that can be achieved within lenvatinib and pembrolizumab in conventional clear cell renal cell cancer. We see that confirmed [in KEYNOTE-B61],” Martin H. Voss, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, told Targeted Oncology^TM in an interview.

Outside of the US and Canada, the label for pembrolizumab was updated to include these data.

About KEYNOTE-B61

KEYNOTE-B61 was a phase 2, single-arm, multicenter trial. A total of 160 patients with previously untreated nccRCC were included.²

Patients with histologically confirmed locally advanced or metastatic nccRCC who did not receive prior systemic treatment, had measurable disease as per RECIST v1.1 criteria, and a Karnofsky performance score of 70% or more were included in the trial. Tumor tissue samples also must have been available.

Once enrolled, pembrolizumab was administered at 400 mg via intravenous infusion every 6 weeks for up to 18 cycles or approximately 2 years in addition to lenvatinib given orally at 20 mg daily. Patients had their disease assessed 12 weeks from allocation, followed by every 6 weeks for 54 weeks, and then every 12 weeks.

The primary end point of the study was overall response rate (ORR) as per RECIST v1.1 criteria by blinded independent central review (BICR). Secondary end points of the trial included clinical benefit rate, disease control rate, duration of response (DOR), and progression-free survival per RECIST v1.1 criteria by BICR. OS and safety were also evaluated as secondary end points.

All patients who received at least 1 dose of study treatment were evaluable for efficacy and safety, and investigators assessed DOR in patients who reached a complete response (CR) or partial response (PR).

Findings showed that the ORR was 51% (95% CI, 43%%), with a CR rate of 8% and a PR of 42% among the patients treated with lenvatinib and pembrolizumab. The median DOR was 19.5 months (range, 1.5+ to 23.5+).¹

There were no new safety signals observed.

"Non-clear cell RCC is an aggressive, challenging-to-treat disease, and our goal is to address those unmet needs and advance care for these patients," said Takashi Owa, chief scientific officer, senior vice president, Eisai Co., Ltd, in a press release. "The addition of efficacy data from the KEYNOTE-B61 trial reinforces the important role of [pembrolizumab] plus [lenvatinib] as a frontline treatment option for adult patients with advanced RCC regardless of histology. We are proud to realize this development through our collaboration with Merck to improve the lives of more people affected by cancer, and we are grateful to the patients and investigators whose involvement made this advancement possible."

About Lenvatinib Plus Pembrolizumab

The combination of lenvatinib and pembrolizumab is the first and only immunotherapy and TKI combination to show data in both clear cell and advanced nccRCC in the FDA-approved label. In 2021, the FDA granted approval to the combination for the first-line treatment of adult patients with advanced RCC.³

Findings from the phase 3 CLEAR trial (NCT02811861) supported this regulatory decision as the combination reduced the risk of disease progression or death by 61% (HR, 0.39; 95% CI, 0.32-0.49; P <.0001) vs sunitinib (Sutent). Additionally, the median progression-free survival observed with the combination was 23.9 months vs 9.2 months for sunitinib.

REFERENCES:

1. New efficacy data for non-clear cell renal cell carcinoma from KEYNOTE-B61 added to LENVIMA® (lenvatinib) US label supporting KEYTRUDA + LENVIMA indication for the first-line treatment of adult patients with advanced RCC. News release. Eisai. June 27, 2024. Accessed August 16, 2024. https://tinyurl.com/2s42545n

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 January 16, 2024. Accessed August 16, 2024. https://clinicaltrials.gov/study/NCT04704219

3. FDA approves Keytruda® (pembrolizumab) plus Lenvima® (lenvatinib) combination for first-line treatment of adult patients with advanced renal cell carcinoma (RCC). News release. Merck and Eisai. August 11, 2021. Accessed August 16, 2024. https://tinyurl.com/55jm7mbv