Abstract 546P
Background
The combination of IV Pac + Pem has demonstrated preliminary antitumor activity in two NSCLC phase I studies. E at 15mg QD plus oPac at 205 mg/m2 QD x 3 days every week is safe and has demonstrated efficacy in treating mBC. E is a , minimally absorbed, oral PGP inhibitor to prevent intestinal oPac efflux. The aims were to determine the safety and tolerability, recommended phase 2 dose (RP2D) of oPac/E in combination with Pem and to evaluate early clinical activity.
Methods
The dose escalation utilized the “3+3” design and eligible patients had metastatic or unresectable solid tumors for which Pem is an FDA approved therapy. The oPac dose range explored was 270-330mg administered for 2 days up to a maximum of 5 days per week x 2 weeks of a 3-week cycle. Pem 200mg IV was administered every three weeks. PK samples were collected for exploratory PK-PD analysis.
Results
In total, 21 patients, age range 45 to 81 years were enrolled including 10 lung cancer, 4 head and neck cancer (H&N), 3 oesophageal cancer, 1 bladder cancer, 1 colon cancer, 1 sarcoma and 1 uveal cancer. The MTD was not reached. 1[DC1] DLT (febrile neutropenia grade (G) 4) was observed at the 270mg x 4 days dose level. 3 pts experienced neutropaenia (2 pts G3, 1pt G4). 3 pts experienced SAEs related to treatment (neutropenia G3 and G4 and diarrhoea G3). No deaths due to treatment occurred. Clinical activity was seen at all dose levels. Of 15 evaluable pts 6 had a partial response (5 lung cancer, 1 colon cancer), 6 had stable disease (2 lung cancer, 2 H&N, 1 uveal cancer[DC2] , 1 esophageal) and 3 had progressive disease (1 H&N, 1 bladder, 1 oesophageal). PK analysis of oPac identified an approximate linear relationship between dose and AUCt and no difference from historic mono-therapy PK. The study determined 270mg x 3 days per week for 2 weeks (Days 1-3, 8-10) of a 3-week cycle as the RP2D.
Conclusions
The addition of oPac/E to Pem was safe and the study successfully identified the RP2D. Encouraging anti-tumor activity was observed and phase 2 studies evaluating the combination are being planned.
Clinical trial identification
NCT03588039.
Editorial acknowledgement
Legal entity responsible for the study
Athenex Inc.
Funding
Athenex Inc.
Disclosure
W.W. Ma: Financial Interests, Institutional, Principal Investigator: Athenex Inc. P. Singh: Financial Interests, Institutional, Principal Investigator: Athenex. R. Manochakian: Financial Interests, Institutional, Principal Investigator: Athenex. D. Cutler: Financial Interests, Personal, Full or part-time Employment: Athenex. D. Landers: Financial Interests, Personal, Full or part-time Employment: Athenex. W. Chan: Financial Interests, Personal, Full or part-time Employment: Athenex. J. Zhi: Financial Interests, Personal, Full or part-time Employment: Athenex. R. Kwan: Financial Interests, Personal, Full or part-time Employment: Athenex. All other authors have declared no conflicts of interest.