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 Anti-Cancer Agents & Biologic Therapy
Drug Development
Breast Cancer, Metastatic
Colon Cancer
Rectal Cancer
Pancreatic Cancer
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

Abstract

Aim

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.

Methods

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.

Results

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).

Conclusions

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.

Disclosure

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.