PMID- 30014244 OWN - NLM STAT- MEDLINE DCOM- 20180925 LR - 20240426 IS - 1432-0851 (Electronic) IS - 0340-7004 (Print) IS - 0340-7004 (Linking) VI - 67 IP - 9 DP - 2018 Sep TI - Phase I trial of Lipovaxin-MM, a novel dendritic cell-targeted liposomal vaccine for malignant melanoma. PG - 1461-1472 LID - 10.1007/s00262-018-2207-z [doi] AB - INTRODUCTION: In this phase I study using a 3 + 3 dose escalation design, the safety, dose-limiting toxicity (DLT), immunogenicity and efficacy of intravenous Lipovaxin-MM-a multi-component dendritic cell-targeted liposomal vaccine against metastatic melanoma-was investigated. METHODS: Twelve subjects with metastatic cutaneous melanoma were recruited in three cohorts. Patients in Cohort A (n = 3) and Cohort B (n = 3) received three doses of 0.1 and 1 mL of Lipovaxin-MM, respectively, every 4 weeks. Patients in Cohort C (n = 6) received four doses of 3 mL vaccine weekly. Immunologic assessments of peripheral blood were made at regular intervals and included leukocyte subsets, cytokine levels, and Lipovaxin-MM-specific T-cell and antibody reactivities. Tumor responses were assessed by RECIST v1.0 at screening, then 8 weekly in Cohorts A and B and 6 weekly in Cohort C. RESULTS: Of a total of 94 adverse events (AEs) reported in ten subjects, 43 AEs in six subjects were considered to be possibly or probably vaccine-related. Most (95%) vaccine-related AEs were grade 1 or 2, two (5%) grade 3 vaccine-related AEs of anemia and lethargy were recorded, and higher grade AEs and DLTs were not observed. No consistent evidence of vaccine-specific humoral or cellular immune responses was found in post-immunization blood samples. One patient had a partial response, two patients had stable disease, and the remaining patients had progressive disease. CONCLUSIONS: Lipovaxin-MM was well tolerated and without clinically significant toxicity. Immunogenicity of Lipovaxin-MM was not detected. Partial response and stable disease were observed in one and two patients, respectively. FAU - Gargett, Tessa AU - Gargett T AUID- ORCID: 0000-0003-3713-1373 AD - Center for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia. FAU - Abbas, M Nazim AU - Abbas MN AD - Cancer Clinical Trials Unit, Royal Adelaide Hospital, Adelaide, SA, Australia. FAU - Rolan, Paul AU - Rolan P AD - School of Medicine, The University of Adelaide, Adelaide, SA, Australia. FAU - Price, Jason D AU - Price JD AD - Lipotek Pty Ltd, Canberra, ACT, Australia. FAU - Gosling, Katharine M AU - Gosling KM AD - Lipotek Pty Ltd, Canberra, ACT, Australia. FAU - Ferrante, Antonio AU - Ferrante A AD - School of Medicine, The University of Adelaide, Adelaide, SA, Australia. AD - Department of Immunopathology, SA Pathology, Women's and Children's Hospital, Adelaide, SA, Australia. AD - Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia. FAU - Ruszkiewicz, Andrew AU - Ruszkiewicz A AD - Center for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia. AD - Division of Anatomical Pathology, SA Pathology, Adelaide, SA, Australia. FAU - Atmosukarto, Ines I C AU - Atmosukarto IIC AD - Lipotek Pty Ltd, Canberra, ACT, Australia. FAU - Altin, Joseph AU - Altin J AD - Division of Biomedical Science and Biochemistry, Research School of Biology, Australian National University, Canberra, ACT, Australia. FAU - Parish, Christopher R AU - Parish CR AD - ACRF Department of Cancer Biology and Therapeutics, the John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia. FAU - Brown, Michael P AU - Brown MP AD - Center for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia. MichaelP.Brown@sa.gov.au. AD - Cancer Clinical Trials Unit, Royal Adelaide Hospital, Adelaide, SA, Australia. MichaelP.Brown@sa.gov.au. AD - School of Medicine, The University of Adelaide, Adelaide, SA, Australia. MichaelP.Brown@sa.gov.au. LA - eng PT - Clinical Trial, Phase I PT - Journal Article DEP - 20180716 PL - Germany TA - Cancer Immunol Immunother JT - Cancer immunology, immunotherapy : CII JID - 8605732 RN - 0 (Cancer Vaccines) RN - 0 (Liposomes) SB - IM MH - Adult MH - Aged MH - Cancer Vaccines/*administration & dosage/adverse effects/immunology MH - Dendritic Cells/drug effects/*immunology MH - Dose-Response Relationship, Immunologic MH - Female MH - Humans MH - Liposomes/administration & dosage/immunology MH - Male MH - Melanoma/immunology/*therapy MH - Middle Aged MH - Skin Neoplasms/immunology/*therapy MH - Melanoma, Cutaneous Malignant PMC - PMC11028356 OTO - NOTNLM OT - Clinical trial OT - DC-SIGN OT - Dendritic cells OT - Liposomes OT - Melanoma OT - Vaccine COIS- Jason D. Price, Katharine M. Gosling, and Ines I.C. Atmosukarto are employed by Lipotek Pty Ltd. Paul Rolan, Joseph Altin, and Christopher R. Parish are Lipotek shareholders. Paul Rolan and Ines I.C. Atmosukarto are Directors of Lipotek. All other authors declare that they have no conflict of interest. EDAT- 2018/07/18 06:00 MHDA- 2018/09/27 06:00 PMCR- 2018/07/16 CRDT- 2018/07/18 06:00 PHST- 2017/08/14 00:00 [received] PHST- 2018/07/09 00:00 [accepted] PHST- 2018/07/18 06:00 [pubmed] PHST- 2018/09/27 06:00 [medline] PHST- 2018/07/18 06:00 [entrez] PHST- 2018/07/16 00:00 [pmc-release] AID - 10.1007/s00262-018-2207-z [pii] AID - 2207 [pii] AID - 10.1007/s00262-018-2207-z [doi] PST - ppublish SO - Cancer Immunol Immunother. 2018 Sep;67(9):1461-1472. doi: 10.1007/s00262-018-2207-z. Epub 2018 Jul 16.