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 Cytotoxic agents
Therapy
Biological 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

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Disclosure

A. Velasco: membership PharmaMar.

A. Soto-Matos: PharmaMar membership.

S. Szyldergemajn: PharmaMar membership.

All other authors have declared no conflicts of interest.