Neoadjuvant intralesional daromun improves relapse-free survival in stage III melanoma

Results of the phase 3 PIVOTAL trial demonstrated clinically meaningful and statistically significant longer relapse-free and distant metastasis-free survival after neoadjuvant intralesional injection of daromun, compared with surgery alone, in patients with pre-treated stage III melanoma.

Daromun consists of 2 antibody-cytokine fusions as active principles (L19/IL-2 and L19/TNF), which act synergistically to directly kill tumour cells while also inducing a systemic anti-tumour immune response [1]. Previously, daromun showed promising results in a phase 2 study in patients with stage IIIC/IV1a melanoma, achieving an objective response rate of 68% [2].

The aim of the randomised, phase 3 PIVOTAL trial (NCT02938299) was to evaluate the effectiveness and safety of neoadjuvant daromun versus surgery alone in pre-treated, stage IIIB/C melanoma patients. Prof. Axel Hauschild (Universitätsklinikum Schleswig-Holstein, Germany) presented the first results [3].

PIVOTAL randomised 246 participants to an injection of at least 1 cutaneous, subcutaneous, or lymph node lesion with daromun, followed by surgery, or to immediate surgery alone. Adjuvant therapy was allowed at the investigator’s discretion.

Treatment with daromun increased median relapse-free survival (RFS) compared with surgery alone: 16.7 versus 6.8 months (HR 0.59; 95% CI 0.41–0.86; P=0.005). The 2-year RFS rates were 41.6% and 23.6%, respectively. In addition, median distant metastasis-free survival (DMFS) was improved in participants treated with daromun: 28.0 versus 17.8 months (HR 0.60; 95% CI 0.37–0.95; P=0.029). “This difference in DMFS suggests a systemic immune response induced by the local intralesional injection of daromun,” Prof. Hauschild concluded.

Further evaluation of the impact of adjuvant therapy on RFS showed that both daromun and adjuvant therapy contributed to a longer median RFS. It was 5.3 months in participants who had only surgery, 11.7 months in participants who underwent surgery and received adjuvant therapy, 13.8 months in participants who received daromun followed by surgery, and 22.8 months in participants who received daromun, surgery, and adjuvant therapy. Overall survival data is not yet mature.

Daromun showed a manageable safety profile, with mainly local adverse events. The agent is currently being investigated for various skin cancer types.

1. Hemmerle T, et al. Int J Cancer. 2014;134:467-477.
2. Danielli R, et al. Cancer Immunol Immunother. 2015;64:999-1009.
3. Hauschild A, et al. Phase 3 study (PIVOTAL) of neoadjuvant intralesional daromun versus immediate surgery in fully resectable melanoma with regional skin and/or nodal metastases. Abstract LBA9501, ASCO Annual Meeting 2024, 31 May–4 June, Chicago, IL, USA.

Posted on 18 July 202418 July 2024