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 Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Metastatic
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.