Neoadjuvant therapy with nivolumab plus relatlimab is safe and effective in patients with stage III melanoma

Neoadjuvant and adjuvant treatment with nivolumab plus the LAG-3 inhibitor relatlimab achieved high pathologic complete response (pCR) and major pathologic response rates with a favourable toxicity profile. This was shown in a multi-institutional, investigator-initiated, single-arm study.

A pooled analysis of 192 patients from 6 trials has shown improved recurrence-free survival and overall survival in patients with clinical stage III melanoma who achieved a pCR after neoadjuvant immunotherapy or targeted therapy [1]. In addition, a combination of neoadjuvant immunotherapy regimens has shown robust pathologic response with acceptable toxicity in stage III melanoma patients [2]. Also, nivolumab combined with the LAG-3 antibody relatlimab has demonstrated a favourable toxicity profile and responses in both checkpoint-naïve and refractory metastatic melanoma [3].

To evaluate the efficacy and safety of neoadjuvant nivolumab plus relatlimab followed by adjuvant nivolumab plus relatlimab, a single-arm study (NCT02519322) was conducted in 30 patients with clinical stage IIIB/IIIC/IIID/IV surgically-resectable melanoma. The primary endpoint of the trial was pCR rate. Secondary endpoints were relapse-free, event-free, and overall survival, objective response rate, and safety. Patients received nivolumab (480 mg) and relatlimab (160 mg) in weeks 1 and 5. Surgery was conducted at week 9 and specimens were assessed for pathologic response per established criteria. Patients received up to 10 additional doses of nivolumab and relatlimab after surgery. Dr Rodabe Amaria (MD Anderson Cancer Center, TX, USA) presented the first results [4].

The rate of pCR was 59%, and 7% achieved near pCR (<10% viable tumour), resulting in a major pathologic response (pCR + near pCR) of 66%. In addition, 7% of patients achieved a pathologic partial response (10–50% viable tumour) and 27% no pathologic response (≥50% viable tumour). RECIST objective response rate was 57%. The 1-year relapse-free survival for patients with major pathologic response was 100% compared with 80% for patients without (P=0.016; see Figure).

No treatment-related grade 3/4 adverse events occurred during neoadjuvant treatment, and 26% of patients reported a grade 3/4 adverse event that began during adjuvant treatment.

Figure: Improved RFS outcomes for patients with major pathologic response [4]

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   1. Menzies AM, et al. Nat Med. 2021;27:301-309.
   2. Rozeman EA, et al. Lancet Oncol. 2019;20:948-960.
   3. Ascierto PA, et al. Abstract 4998, ESMO 2017, 8–12 Sept, Madrid, Spain.
   4. Amaria RN, et al. Neoadjuvant and adjuvant nivolumab (nivo) with anti-LAG3 antibody relatlimab (rela) for patients (pts) with resectable clinical stage III melanoma. Abstract 9502, ASCO 2021 Virtual Meeting, 4–8 June.

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Posted on 12 August, 202129 February, 2024