161P - Safety of TrimelVax vaccine for patients with advanced melanoma: Clinical results

Background

In 2009, a clinical trial treated patients with advanced melanoma, with TAP cells stimulated ex vivo with tumor lysates (Trimel), achieving long survival results (López et al. JCO 2009). Based on these results, direct inoculation of TrimelVax vaccine was tested in a murine model of B16F10 melanoma. The vaccine consisted of tumor lysates (from 3 human melanoma cell lines, heat-shock treated and then lysed) combined with a hemocyanin. The murines were treated with either TrimelVax, nivolumab, both or a serum control. Murines exposed to TrimelVax and TrimelVax plus nivolumab achieved longer survival, better tumor response, and higher infiltration of TCD8 lymphocytes in tumors, as compared to controls (Gleisner et al. JIC 2021).

Methods

We conducted a phase 1 clinical trial to test the safety of TrimelVax in patients with unresectable stage III or IV melanoma after first-line treatment with anti-PD1 antibody. The trial is registered in ClinicalTrials.gov (NCT06556004) and approved by the institutional ethics committee. We aimed to administer the vaccine every four weeks for four doses to 20 patients. The main objective was to assess the therapy's safety, according to CTCAE 5.0. Secondary objectives were: specific immune response, tumor response, progression-free survival (PFS), and overall survival (OS).

Results

Between January 2022 and November 2023, 20 patients were recruited. 19 had progressed on previous anti-PD1 treatment, and one had stopped treatment due to unacceptable toxicity. Two patients did not start treatment for non-medical reasons, and one was excluded due to failure to meet selection criteria, five patients did not complete the intervention due to progression, and 12 patients completed 4 doses. Nine patients presented adverse events (AE) with two grade 3 AE (hepatic and cutaneous). All these patients recovered from the AE and completed the protocol. Toxicities observed corresponded mainly to immune-mediated effects. Five patients achieved stable disease, and 12 had progressive disease as the best response. The observed PFS of the 17 patients treated was 4.5 months, with an OS of 11.6 months.

Conclusions

TrimelVax presented an adequate safety profile in this trial. More studies are needed to evaluate the effectiveness of this therapy.

Clinical trial identification

NCT06556004.

Legal entity responsible for the study

Universidad de Chile.

Funding

Conicyt (Comisión Nacional de Investigación Científica y Tecnológica), Chile ANID, FONDAP 152220002.

Disclosure

All authors have declared no conflicts of interest.