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

Daromun consists of two antibody-cytokine fusions as active principles, L19IL2 and L19TNF, which act synergistically to directly kill tumor cells while also inducing a systemic antitumor immune response¹. Previously, daromun showed promising results (ORR 68%) in a phase 2 study in patients with stage IIIC/IV1a melanoma².

The aim of the phase 3, randomized PIVOTAL trial (NCT02938299) was to evaluate the effectiveness and safety of neoadjuvant daromun versus surgery alone in patients with pretreated stage IIIB/C melanoma. Dr. Axel Hauschild, MD, of Universitätsklinikum Schleswig-Holstein, in Germany, presented the first results³.

PIVOTAL randomly assigned 246 patients to injection in at least one cutaneous, subcutaneous, or lymph node lesion with daromun followed by surgery or immediate surgery alone. Adjuvant therapy was allowed at the investigator’s discretion.

Treatment with daromun increased median relapse-free survival (mRFS): 16.7 months versus 6.8 months (HR 0.59, 95% CI 0.41-0.86; P=0.005). RFS rates at 2 years of follow-up were 41.6% and 23.6%, respectively. In addition, median distant metastasis-free survival (DMFS) was improved in patients treated with daromun: 28.0 months 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”, Dr. Hauschild concluded.

Evaluation of the impact of adjuvant treatment on RFS showed both daromun and adjuvant therapy contributed to the longer mRFS. MPSF was 5.3 months in patients who had only surgery, 11.7 months in patients who had surgery and adjuvant therapy, 13.8 months in patients who received daromun followed by surgery, and 22.8 months in patients who received daromun surgery and adjuvant therapy.

Overall survival data are not yet mature and will be presented later. Daromun showed a manageable safety profile with mainly local AEs and is currently being investigated in various skin cancer types.

Medical writing support was provided by Marten Dooper, PhD.

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