Researchers investigated the outcomes of treating patients with advanced melanoma, including patients who previously received adjuvant therapy, with antilymphocyte-activation gene 3 (LAG-3) antibody (Ab) fianlimab and anti-programmed cell death protein 1 (PD-1) Ab cemiplimab. The findings from the phase 1 study were presented at the 2023 ASCO Annual Meeting. 

Three cohorts of adult patients with advanced unresectable or metastatic melanoma (excluding uveal melanoma) who were antiPD(L)-1 treatment-naïve were enrolled in the study. A total of 98 patients were enrolled in the study, with the median age being 68 years old, 60.2% being male, and 89.8% being White. 

Some 2% of patients had received prior metastatic treatment (not antiPD-1). Another 23.5% of patients had received prior systemic treatment in the adjuvant/neoadjuvant setting and were disease-free for more than 6 months. Of these patients, 13% had been treated with an antiPD-1 agent (nivolumab or pembrolizumab).

All participants received 1600 mg of fianlimab plus 350 mg of cemiplimab, administered intravenously every 3 weeks, for 12 months. Patients received an additional 12 months of treatment if clinically indicated. Tumor measurements were taken every 6 weeks for 24 weeks, and then every 9 weeks thereafter. Median follow-up occurred after 12.6 months of treatment, which had a median duration of 32.9 weeks.

The study findings indicated that grade 3 or higher treatment-emergent adverse events (TEAEs), serious TEAEs, and immune-related AEs (irAEs) occurred in 43.9%, 32.7%, and 65.3% of patients, respectively. The percentage of patients who discontinued the treatment due to TEAEs was 16.3%. 

The rates of irAEs in patients who received the fianlimab and cemiplimab combination were similar to the anticipated rates for those receiving antiPD-1 monotherapy, with the exception of adrenal insufficiency with 12.2% (all grades) and 4.1% (grade 3 or higher). Among patients receiving the combination, the overall objective response rate was 61.2% (12 complete responses; 48 partial responses), and the median duration of response was not reached (95% CI: 22.6-not estimated [NE]). The estimated median progression-free survival (mPFS) was 15.3 months (95% CI: 9.4-NE). 

In patients who had any prior adjuvant treatment, the objective response rate was 60.9% (14 complete responses; 23 partial responses), and the mPFS was 13.3 months. In patients who received prior antiPD-1 adjuvant treatment, the objective response and mPFS were 61.5% (8 complete responses; 13 partial responses) and 11.8 months, respectively. The median duration of response was not reached in either group of patients.

Treatment for advanced melanoma with fianlimab and cemiplimab demonstrated high clinical activity, similar to other approved combinations of immune checkpoint inhibitors in the same clinical setting, researchers concluded. 

“This is the first indication that dual LAG-3 blockade can produce high level of activity with significant [objective response rates] in patients with advanced melanoma post adjuvant antiPD-1 treatment,” researchers said.  

The authors noted a phase 3 trial of the fianlimab and cemiplimab combination in treatment-naïve patients with melanoma is currently ongoing.

Reference:
Hamid O, Lewis KD, Weise AM, et al. Significant durable response with fianlimab (anti-LAG-3) and cemiplimab (anti-PD-1) in advanced melanoma: Post adjuvant PD-1 analysis. J Clin Oncol. 2023;41(16): abstract 9501. doi:10.1200/JCO.2023.41.16_suppl.9501