391P - Lurbinectedin (PM01183) plus paclitaxel (P), recommended dose (RD) expansion results with or without the addition of bevacizumab (Bev) in patients...

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Drug Development
Presenter Alexander Drilon
Citation Annals of Oncology (2016) 27 (6): 114-135. 10.1093/annonc/mdw368
Authors A. Drilon1, E. Garralda2, A. Stathis3, S. Szyldergemajn4, D. Hyman1, V. Boni2, G. Griguolo3, E. Jimenez Martinez4, V. Makker1, L. Canziani3, C. Fernandez Teruel4, A. Soto-Matos4, C. Sessa3, E. Calvo2
  • 1Oncology, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 2Oncology, START-Madrid, Madrid/ES
  • 3Oncology, IOSI-Ospedale San Giovanni, 6500 - Bellinzona/CH
  • 4Clinical, PharmaMar, Colmenar Viejo/ES

Abstract

Background

The identified RD of PM01183 + P is PM01183 2.2 mg/m2 on Day (D)1 + P 80 mg/m2 D1&8 q3w. We provide updated results after RD expansion (A), and after Bev 15 mg/kg addition on D1 (B).

Methods

RECIST v1.1 evaluable pts ≤ 75 years (y) old, with ECOG PS 0-1, adequate organ function and ≤ 3 prior advanced lines were eligible. Prior taxanes were allowed if last dosed ≥ 3 months prior; prior weekly P or NAB-P were excluded. P was discontinued after 18 weeks and pts continued on PM01183 alone (A) or plus Bev (B). Pharmacokinetics (PK) was assessed in C1.

Results

As of April 2016, 37/12 pts were treated (cohort A/B, accordingly); 2/37 and 3/12 experienced a dose-limiting toxicity (DLT) in Cycle 1, respectively. 32/10 were evaluable for efficacy. PK results were in line with published data.

Cohort n = pts DLT (%) ORR (95%CI) DOR months Tumor Type (%) CTC ARs G1-2 % CTC ARs G3 % CTC ARs G4 (%) Prior Taxanes Prior Bev
A (n = 37/32) Myelo suppression (5%) 40% (24-59) 4.2 (1.2-12.7+) NSCLC (16); SCLC (14), Breast (22); Endometrial (35), EOC (8) Other (5); Anemia Fatigue Nausea Vomiting Diarrhea PSN 72 57 51 43 22 35 Neutropenia Anemia ALT ↑ FN Thrombopenia Fatigue Rash Nausea Vomiting 28 22 11 3 3 3 3 3 3 Neutropenia (28) 57% 14%
B (n = 12/10) Myelo suppression (17%) Colonic Perforation (8%) 50% (19-81) 6.2 (2.4-10.9+) EOC (42) Non-squamous NSCLC (58) Anemia Fatigue Nausea Diarrhea Vomiting PSN 92 58 42 33 17 17 Neutropenia FN Anemia Fatigue Sepsis Colonic fistula 33 17 8 8 8 8 Neutropenia (25) Colonic perforation (8) 67% 25%

CI, confidence interval; CTCAE (v4.03), common toxicity criteria adverse reactions (related/unknown); EOC, epithelial ovarian cancer; G. grade; DOR; duration of response; NSCLC; non-small cell lung cancer; ORR, overall response rate; PSN; neurotoxicity; FN: febrile neutropenia

Conclusions

At the RD, PM01183/P has an acceptable safety profile and remarkable antitumor activity, even in pts previously exposed to taxanes/Bev. CSFs prophylaxis was not required at the RD. Neurotoxicity was not dose-limiting. The addition of Bev to PM01183/P RD was feasible but it seems more pts might experience DLTs in C1. No Drug-Drug Interactions were observed.

Clinical trial identification

NCT01831089

Legal entity responsible for the study

PharmaMar

Funding

PharmaMar

Disclosure

S. Szyldergemajn, E. Jimenez Martinez, C. Fernandez Teruel, A. Soto-Matos: PharmaMar employee and stock ownership. D. Hyman: Consulting ATARA. E. Calvo: Consultan or Adviso: Astellas Ph, GlaxoSm, Janssen-Ci, Lilly, Novartis, Pfizer, PharmaMar, Roche/Ge, Sanofi Research Funding: All previous plus: Eisai, Merck Ser, Merck Sp & D, Millennium, OncoMed, Psi Oxus, Spectrum Ph Honoraria: Astellas Ph, Novartis. All other authors have declared no conflicts of interest.