482P - Lurbinectedin (PM01183) on days (D) 1 & 8 in combination with capecitabine (XEL) in patients (pts) with metastatic breast (MBC), colorectal (CRC) o...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anticancer Agents
Clinical Research
Colon and Rectal Cancer
Pancreatic Cancer
Breast Cancer
Basic Scientific Principles
Biological Therapy
Presenter Tamara Sauri
Citation Annals of Oncology (2014) 25 (suppl_4): iv146-iv164. 10.1093/annonc/mdu331
Authors T. Sauri1, P. Aftimos2, S. Szyldergemajn3, E. Elez4, P. Barthelemy2, R. Moreno3, A. Soto-Matos3, S. Extremera3, J. Tabernero1, A. Awada5
  • 1Oncology, Vall d'Hebron, 08035 - Barcelona/ES
  • 2Oncology, Institut Jules Bordet, Brussels/BE
  • 3Clinical, PharmaMar, 28770 - Colmenar Viejo, Madrid/ES
  • 4Medical Oncology, Hospital Vall d'Hebron, 08035 - Barcelona/ES
  • 5Medical Oncology, Institute Jules Bordet, 1000 - Brussels/BE



PM01183 is a promising new agent. It exerts antitumor activity through inhibition of trans-activated transcription and modulation of tumor microenvironment. PM01183 single-agent recommended dose (RD) is 5 mg D1 & 8 q3wk, with activity observed in PaC and MBC, but limited in pretreated CRC, and reversible myelosuppression as its main dose-limiting toxicity (DLT). Preclinical synergism/additivity in combination with 5FU/XEL was reported, thus prompting this phase I study.


Adult MBC, CRC or PaC pts ≤ 75 years (y) old, with ECOG PS 0-1, adequate major organ function and <3 prior lines were included following a 3 + 3 design. Dose level (DL) #1 was PM01183 2 mg on D1 & 8 + XEL 1650 mg/m2 b.i.d. from D1 to 14 q3wk. The highest DL with < 1/3 of pts having DLTs in Cycle 1 would be the RD. Prior adjuvant XEL was allowed if relapse >6 months after discontinuation.


As of 20 April 2014, 14 pts were treated at 2 DLs; 8 (57%) were males, median age: 55 y (r: 35-74), median BSA: 1.9 mg/m2 (r: 1.5-2.2). Median prior lines was 1.5 (r: 0-2) and 10 (71%) pts received prior XEL or infusional 5FU. DL#2 (PM01183 3 mg/D1& 8) was the maximal dose reached, as 2 of 5 evaluable pts had DLT as grade (G)4 neutropenia >3 D or delay of Cycle 2 for >15 D due to neutropenia. DL#1 was expanded to 9 evaluable pts and none had DLT, defining it as the RD. Common G1/2 toxicities across DLs in ≥15% of pts were: nausea, diarrhea, fatigue and HFS. G3 toxicities (other than reversible neutropenia) at any DLs were: anemia, pulmonary embolism, rash and DVT (1 each). One pt had G4 thrombocytopenia; no other G4 toxicities were reported. Antitumor activity: CRC (n = 6): 2 partial responses (PR) and 3 stable diseases for > 4 months (SD4); MBC (n = 3): one PR; PaC (n = 4): 2 SD4. Globally 23% response rate (RR) and 62% of 13 evaluable pts had clinically meaningful benefit from the combination. Median time to progression (TTP) was 32 wks (95%CI: 13-34).


The combination of PM01183 and XEL is tolerable, with no DLT occurring at the RD of PM01183 2 mg on D1 & 8 + XEL 1650 mg/m2 b.i.d. q3wk. Promising activity was observed. A simplest schedule without the D8 infusion is being explored. Dose escalation is ongoing.


S. Szyldergemajn, R. Moreno, A. Soto-Matos and S. Extremera: I am employee of PharmaMar and I am stock ownership. All other authors have declared no conflicts of interest.