PM01183 is a new anticancer drug. Single agent efficacy is reported in MBC and in ovarian cancer, myelosuppression being a dose-limiting toxicity (DLT) in phase I studies. A recommended dose (RD) for PM01183 given on D 1 and 8 with XEL was previously defined. We explored a simplified schedule where PM01183 is given on D1 q3wk only.
Adult MBC, CRC or PaC pts, ≤ 75 years (y) old, with ECOG PS 0-1, adequate major organ function and
As of April 2016, 65 eligible pts were treated, 64/63 were evaluable for DLT/efficacy: 25/22/16 had MBC/CRC and PaC, respectively; 40% were males, median age was 57 y (r: 29-74) and ECOG PS= 1 in 42%. MBC pts had a median of 1 prior chemotherapy lines, CRC/PaC had 2. RD was defined as PM01183 2.2 mg/m2 D1+ XEL 1650 mg/m2 b.i.d. D1-14 q3wk. At the RD, 3 of 35 (9%) evaluable pts had DLT, all three were lack of compliance due to myelosuppression. At the RD, 14/3% of pts had grade (G) 4 neutropenia or thrombocytopenia, respectively; none had febrile neutropenia or any G4 non-hematological toxicity; G3 fatigue or hypertension occurred once, each. G1/2 toxicities in ≥10% at the RD were: nausea, diarrhea, vomiting, fatigue, mucositis and HFS. Efficacy: 12/25 MBC pts responded for a 48% response rate (95%CI: 28-69%), including 3/8 with triple negative tumors. Median TTP in MBC is 26+ wk (95%CI: 16-75), 10 pts are ongoing as May 2016. PM01183 pharmacokinetics was unaffected by XEL administration.
The combination of PM01183 on D1 with XEL is feasible and has a favorable safety profile. Durable responses occurred in half of MBC pts, confirmatory studies are warranted. Updated data will be presented.
Clinical trial identification
Legal entity responsible for the study
E. Calvo: Consultant or Advisor: 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. S. Szyldergemajn, C. Fernandez Teruel, A. Soto-Matos: PharmaMar employee ans stock ownership J. Tabernero: Consultant/Advisory role: Amgen, Bayer, Boehringer Ingelheim, Celgene, Chugai, Lilly, MSD, Merck Serono, Novartis, Roche, Sanofi, Symphogen, Takeda and Taiho. All other authors have declared no conflicts of interest.