484P - Lurbinectedin (PM01183) in combination with gemcitabine (GEM). Preliminary results of an ongoing phase IB study

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Anti-Cancer Agents & Biologic Therapy
Presenter Emiliano Calvo
Authors E. Calvo1, L.P. Ares2, M. Forster3, I.L. Calderero2, A. Cubillo1, A. Velasco4, V. Boni1, D. Wilkins3, A. Soto-Matos5, S. Szyldergemajn4
  • 1Oncology, Hospital Sanchinarro/START, 28050 - Madrid/ES
  • 2Oncology Service, Hospital Virgen del Rocio, 41013 - Seville/ES
  • 3Oncology, University College of London Hospital, WC1E 6BT - London/UK
  • 4Clinical Operations, PharmaMar, 28770 - Colmenat Viejo, Madrid/ES
  • 5Clinical, PharmaMar, 28770 - Colmenat Viejo, Madrid/ES



PM01183 is a new anticancer agent. It exerts a wide anti-tumour activity through minor groove DNA-binding. Pre-clinical evidence of synergism has been observed in combination with GEM. Single agent PM01183 has clinical activity in pancreatic and platinum-resistant ovarian cancer. Reversible neutropenia and high emetogenic potential are the main single agent toxicity.


Informed and consented adult patients (pts) were included. The starting dose was PM01183 2.5 mg + GEM 800 mg/m2, on Days 1 and 8 q3wk. The dose was escalated in cohorts of 3-6 pts aiming to define the maximum tolerated dose (MTD). The highest dose reached with less than 1/3 of at least 9 pts having dose-limiting toxicities (DLTs) in Cycle 1 will be the recommended dose (RD). Age was restricted up to 75 years, PS-ECOG 0-1, have adequate major organ function and no more than 2 prior chemotherapy lines. Prior adjuvant GEM was allowed if relapse occurred >6 months.


As of MAY 2012, 23 pts were treated across 4 dose levels (DL), 8 (35%) were female, median age was 60 (37–72). NSCLC (n = 12; 52%), pancreatic/biliary tract (n = 5; 22%) and gynaecological (n = 4; 17%) were the most frequent tumour types. Dose escalation proceeded until the MTD was reached: DL 4 PM01183 3.5 mg + GEM 1000 mg/m2. Three pts experienced DLTs: Day 8 omission (neutropenia), febrile neutropenia, neutropenic infection/sepsis and grade 4 thrombocytopenia. One fatal sepsis occurred at the MTD. DL 3 (PM01183 3.5 mg + GEM 800 mg/m2) expansion as possible RD is ongoing. PM01183/GEM seems well tolerated at doses below the MTD. Other toxicities in addition to reversible myelosuppression were mild nausea/vomiting, asymptomatic LFTs increases, pneumonia, anaemia or fatigue. Evidence of activity includes: 2/12 partial (PR) + 1/12 complete response (CR) in NSCLC (2 pts are ongoing after 13+ and 10+ cycles) and 1/4 PR in gynecological. No pharmacokinetic interaction was observed.


The combination of PM01183 and GEM seems feasible with an acceptable safety profile below the MTD: PM01183 3.5 mg+ GEM 1000 mg/m2. RD cohort expansion is currently ongoing. The combination is showing promising anti-tumour activity. Updated results will be presented in the meeting.


A. Velasco: membership PharmaMar.

A. Soto-Matos: PharmaMar membership.

S. Szyldergemajn: PharmaMar membership.

All other authors have declared no conflicts of interest.