480P - Single institution phase I trial of the novel compound first-in-class PDM08 in refractory solid tumors (NCT01380249)

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Clinical Research
Basic Scientific Principles
Presenter Jorge Barriuso
Authors J. Barriuso1, I. Soria2, V. Moreno3, M. Coronado4, I. Galicia5, M.A. Figueredo2, J. Frias6, J. Feliu7, A. Carcas6, J.L. Subiza2
  • 1Oncology Translational Unit, La Paz University Hospital, 28046 - Madrid/ES
  • 2Inmunology Department, San Carlos Hospital, Madrid/ES
  • 3Oncology Phase I Unit, La Paz University Hospital, 28046 - Madrid/ES
  • 4Nuclear Medicine, La Paz University Hospital, Madrid/ES
  • 5Ucicec, La Paz University Hospital, Madrid/ES
  • 6Pharmacology, La Paz University Hospital, Madrid/ES
  • 7Medical Oncology, La Paz University Hospital, 28046 - MADRID/ES



PDM08 is a synthetic derivative of the pyroglutamic acid with anti tumor effect in different murine cancer models. The absence of direct effect on tumour cells and the antitumor activity found in immunocompetent models indicates an immune response mediated mechanism. The aim was to assess the tolerability and safety profile of PDM08.


PDM08 was administered twice a week for four-week cycles. An accelerate escalation phase was chosen with cohorts of 2 patients (pts) that had the possibility of escalate once to the next dose level if no grade ≥2 toxicity and no progressive disease were observed. An expansion cohort was planned at the MTD or the optimal biological dose (OBD). Extensive pharmacokinetic and pharmacodynamic (PD) data were collected. Preliminary efficacy was evaluated by PET-CT.


Since July 2011, 17 patients (pts) were recruited into 8 different dose levels (4pts were escalated) ranged from 0.560 mg to 56 mg. Pt characteristics were: males 52.9%. Median age: 68 (28-76). ECOG 0: 64.7%. Median of previous treatments was 3 ranged 2 to 5. 3 pts presented G1 headache. No DLTs were found. The best outcome was stable disease (SD) for 5 pts (4 colorectal and 1 endometrial), one being stable for 12 weeks, one 14 weeks and one remains stable after 21 weeks. 12.9% of the lesions evaluated by PET-CT showed a reduction in the maximum Standard Uptake Value (SUV) of 18-FDG. A pooled analysis of PD data from patients with the best response showed a statistically significant increased in serum levels of IL-17A, IL-13, IL-4, IL-5, TNFα, IL-22 and IL-1� (p < 0.05) from baseline. Interestingly patients without benefit showed higher basal levels of these cytokines. The analysis of blood cell populations in pts with SD found a trend to increase the absolute numbers of NKT (CD56, CD4), neutrophils (CD45, CD15, CD16b) and some specific markers of Myeloid-derived suppressor cells (CD11b, CD33). The OBD derived from PD changes was 56 mg.


PDM08 is the first compound of a new class of drugs that can be dose-escalated safely in an accelerated manner and has promising activity. PD results suggest that PDM08 is boosting the innate immune response against cancer cells confirming preclinical data.


All authors have declared no conflicts of interest.