223O - Anti-tumor activity of PM01183 (lurbinectedin) in BRCA1/2-associated metastatic breast cancer patients: results of a single-agent phase II trial

Date 08 October 2016
Event ESMO 2016 Congress
Session Breast cancer, metastatic
Topics Anticancer Agents
Breast Cancer
Biological Therapy
Presenter Judith Balmaña
Citation Annals of Oncology (2016) 27 (6): 68-99. 10.1093/annonc/mdw365
Authors J. Balmaña1, C. Cruz1, B.K. Arun2, M. Telli3, J. Garber4, S. Domchek5, C.M. Fernandez6, C. Kahatt6, S. Szyldergemajn6, A. Soto-Matos6, A. Perez de la Haza6, J.A. Perez Fidalgo7, A. Lluch-Hernandez7, S. Antolin8, N.M. Tung9, L.T. Vahdat10, R. Lopez11, S.J.J. Isakoff12
  • 1Medical Oncology, Hospital Vall d’Hebron and Vall d’Hebron Institute of Oncology, 08035 - Barcelona/ES
  • 2Breast Medical Oncology, MD Anderson Cancer Center, 77030 - Houston/US
  • 3Medical Oncology, Stanford University Medical Center, Stanford/US
  • 4Medical Oncology, Dana Farber Cancer Institute, Boston/US
  • 5Medical Oncology, Hospital of the University of Pennsylvania, Philadelphia/US
  • 6Clinical Development, PharmaMar SA, 28770 - Colmenar Viejo/ES
  • 7Medical Oncology, Hospital Clinico Universitario de Valencia, Valencia/ES
  • 8Medical Oncology, Complejo Universitario Hospitalario La Coruña, A Coruna/ES
  • 9Medical Oncology, Beth Israel Deaconess Medical Center, Boston/US
  • 10Medical Oncology, Weill Cornell Medicine, New York/US
  • 11Medical Oncology, Complejo Hospitalario Universitario de Santiago de Compostela, 15706 - Santiago de Compostela/ES
  • 12Medical Oncology, Massachusetts General Hospital, Boston/US



PM01183 (lurbinectedin) is a new anticancer drug that blocks trans-activated transcription, induces DNA double-strand breaks and modulates the tumor microenvironment. PM01183 activity has been observed in different tumor types, and in patients resistant to platinum-based chemotherapy (CT). The activity observed against homologous-recombination-deficient cell lines prompted a phase II trial in metastatic breast cancer (MBC) patients (pts) with deleterious germline BRCA mutations (BRCA+).


BRCA+ MBC pts pretreated with ≤ 3 CT regimens in the advanced/metastatic setting, measurable disease per RECIST v1.1, performance status (PS) ≤ 1, and adequate major organ function were treated with PM01183 IV q3wk. A protocol amendment adjusted the starting dose from 7 mg fixed dose (FD) to 3.5 mg/m2 to improve safety. Primary endpoint was overall response rate (ORR) by RECIST v1.1 with further development of PM01183 if ≥ 17 responses of 53 evaluable pts were confirmed.


As of May 2016, 54 eligible pts (median age 43 years, median 1 prior advanced CT) have been treated (35 with 7 mg FD; 19 with 3.5 mg/m2). PS 0: 30 pts; prior anthracyclines: 45 pts, taxanes: 47 pts, platinum: 27 pts, PARP inhibitors: 9 pts; >2 metastatic sites: 33; BRCA 1: 30 pts; triple negative: 31 pts.

Median cycles (range) 4 (1–24)
Best overall response n = 51 evaluable
CR 1 (2%)
PR 19 (37%)
SD 22 (43%)
PD 9 (18%)
ORR (95%CI) 39% (26–54) 37 / 44% (7 mg FD / 3.5 mg/m2)
- Platinum pretreated 23% (9–44)
Median duration of response months (95%CI) 4.6 (3.4–11.3)
Progression-free survival months (95%CI) 4.1+ (2.6–6.0)

Most common grade (G) 3–4 related adverse events (7 mg FD / 3.5 mg/m2) were (%): neutropenia 71 / 50 (G4: 51/6); febrile neutropenia 29 / 6; thrombocytopenia 26 / 6 (G4; 20/0); G3 fatigue 17 / 17; transaminase increase 26 / 11 (G4; 3/0); and G3 nausea 9 / 6.


Primary endpoint was met. PM01183 is an active drug in BRCA+ MBC, regardless of prior platinum treatment. At 3.5 mg/m2, the tolerance improved notably, while maintaining the efficacy. Further development is warranted in this indication and a Phase 3 trial is planned.

Clinical trial identification


Legal entity responsible for the study

PharmaMar S.A.


PharmaMar S.A.


J. Balmaña: Receipt of grants / research supports; PharmaMar. Paticipation in a company sponsored speaker's bureau; AstraZeneca.

C.M. Fernandez: PharmaMar employee. C. Kahatt, S. Szyldergemajn, A. Soto-Matos: PharmaMar employee and stock ownership. A. Perez de la Haza: PharmaMar employee. All other authors have declared no conflicts of interest.