Abstract 551P
Background
The recommended dose (RD) of lurbinectedin in non-Japanese patients (pts) is 3.2 mg/m2 on Day 1 every three weeks (q3wk). Previous dose escalation in Japanese pts resulted in a maximum tolerated dose (MTD) of 3.2 mg/m2 on Day 1 q3wk. Neutropenia was the main dose-limiting toxicity (DLT). A new dose escalation was done with primary granulocyte colony-stimulating factor (G-CSF) prophylaxis.
Methods
Japanese pts with solid tumours (excluding colorectal cancer or central nervous system primary tumors), adequate organ function and ECOG performance status 0-2 were treated at 2 dose levels (3.2 and 3.5 mg/m2) with primary G-CSF prophylaxis, using a 3+3 escalation design.
Results
Eleven pts (4 female/7 male) were treated and evaluated for safety and efficacy. Median (range) age was 61 (40-77) years, albumin was 4.3 (3.2-5.0) g/dL, and number of previous lines was 3 (1-3) lines. Tumors comprised breast (n=2), biliopancreatic (n=2), small cell lung cancer (n=1), endometrial (n=1) and oropharyngeal (n=1), among others. The two pts treated at 3.5 mg/m2 had DLTs: grade (G) 4 ventricular arrhythmia associated with G4 neutropenia and G4 thrombocytopenia; and delayed G4 transaminase increase in Cycle 2. Two of 9 pts (22.2%) treated at 3.2 mg/m2 had DLTs: G4 thrombocytopenia. 3.2 mg/m2 was defined as the RD with primary G-CSF prophylaxis. Main G3/4 adverse events at the RD were hematological: G3 thrombocytopenia (n=2 pts; 22.2%) and G4 neutropenia (n=1; 11.1%). G3/4 non-hematological toxicities were G3 transaminase increase (n=2; 22.2%) and G3 pulmonary infection (n=1; 11.1%). All pts at the RD had stable disease (SD) as best response, with long-lasting stabilizations (SD>4 months) in 4 pts (44.4%). The pharmacokinetic (PK) profile at the RD was similar to that found in non-Japanese pts, with mean (standard deviation) total body clearance 13.9 (8.2) L/h, half-life 42.5 (12.5) h, and volume of distribution at steady- state 414.9 (196.6) L.
Conclusions
The RD of lurbinectedin given on Day 1 q3wk with primary G-CSF prophylaxis in Japanese pts is 3.2 mg/m2. This RD was associated with mild toxicity. Main DLTs were hematological. Japanese pts showed a similar PK profile compared to non-Japanese pts.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
PharmaMar.
Funding
Has not received any funding.
Disclosure
S. Takahashi: Honoraria (self): Daiichi Sankyo, Sanofi, Eisai, Bayer, Taiho Pharmaceutical, MSD, Novartis, Chugai Pharma, AstraZenca, Astellas Pharma, Bristol-Myers Squibb Japan, Ono Pharmaceutical, Kyowa Hakko Kirin, Nihonkayaku, Pfizer, Lilly Kapan; Advisory/Consultancy: Bayer; Research grant/Funding (self): Daiichi Sankyo, Sanofi, Eisai, Bayer, Taiho Pharmaceutical, MSD, Novartis, Chugai Pharma, AstraZenca, Bristol-Myers Squibb, Lilly, Ono Pharmaceutical, PharmaMar, Pfizer/EMD Serono; Travel/Accommodation/Expenses: Daiichi Sankyo, Novartis. T. Shimizu: Honoraria (self): Daiichi Sankyo, Boehringer; Advisory/Consultancy: Takeda Oncology; Research grant/Funding (self): Novartis, Eli Lilly, Daiichi Sankyo, Bristol-Myers Squibb, Symbio Pharmaceuticals, Takeda, 3D-Medicine, AstraZeneca, Eisai, AbbVie, Incyte, Astellas Pharma, Chordia Therapeutics, Five Prime, PharmaMar; Travel/Accommodation/Expenses: Eisai, Takeda Oncology. T. Doi: Advisory/Consultancy: Lilly Japan, Chigai Pharma, Kyowa Hakko Kirin, MSD, Daiichi Sankyo, Amgen, Sumitomo Dianippon, Taiho Pharmaceutical; Research grant/Funding (self): Taiho Pharmaceutical, Novartis, Merck Serono, Astellas Pharma, MSD, Janssen, Boehringer Ingelheim, Takeda, Pfizer, Lilly Japan, Sumitomo Group, Chugai Pharma, Kyowa Hakko Kirn, Daiichi Sankyo, Celgene, Bristol-Myers Squibb, AbbVie, Quintiles. J.A. Lopez-Vilarino: Honoraria (self), Shareholder/Stockholder/Stock options: PharmaMar. R. Nunez Martin: Honoraria (self): PharmaMar. C. Kahatt: Honoraria (self), Shareholder/Stockholder/Stock options: PharmaMar. C. Fernandez Teruel: Shareholder/Stockholder/Stock options: PharmaMar. A. Zeaiter: Honoraria (self), Shareholder/Stockholder/Stock options: PharmaMar. All other authors have declared no conflicts of interest.