Phase 2 trial of talabostat and docetaxel in patients with stage IIIb/IV NSCLC

Abstract

7120 Background: Talabostat (T) is an oral inhibitor of dipeptidyl peptidases such as fibroblast activation protein found on the stroma of tumors. Administration of T stimulates cytokine and chemokine production in humans and animals. In a mouse xenograft model, T significantly enhanced the activity of docetaxel in the A549 model of NSCLC. Methods: Open-label, single-arm, Phase 2 study in up to 41 evaluable patients with Stage IIIB/IV NSCLC using the Simon 2-stage design. Two responses (PR or CR) by WHO criteria required in the first 21 evaluable patients (defined as completion of 2 cycles with a response assessment by the investigator) to expand enrollment to 41. Up to six 3-week cycles of docetaxel (D) 75mg/m2 (Day1) with appropriate pre-medication and T-200μg administered orally BID Days 2–15. Dose-escalation of T to 300μg BID allowed in subsequent cycles depending on tolerability. Single-agent T may be continued past 6 cycles at the discretion of the investigator. Prior failure of a platinum-based therapy required with no more than 2 prior regimens allowed. ECOG PS 0–1. Primary endpoint is disease response; secondary endpoints include survival, progression-free survival, and incidence of clinically-significant events of neutropenia or anemia. Results: In the first 21 evaluable patients (10 men, 11 women), the median age is 58 (range 34–80); 14 patients had 1 prior treatment and 7 had 2. Partial responses have been seen in 2 patients. The median PFS is 19 weeks. 8 patients have continued on single-agent T beyond 6 cycles, 4 of whom had SD for at least an additional 6 weeks. The most frequently reported adverse events are edema NOS/peripheral (71%), fatigue (57%), neutropenia and leukopenia (each 43%), cough, hypotension, LDH increase, and arthralgia (each 29%). Grade 3/4 events included neutropenia, leukopenia (each 25%), and febrile neutropenia, edema, and dyspnea (all 10%). 6 patients have died during the study; 5 due to PD and one to an unspecified cardiovascular event. Conclusions: In the initial cohort of 21 patients, 2 PRs were reported. The median PFS is 19 weeks. The most common AEs are edema, fatigue, and neutropenia/leukopenia. Enrollment continues. Updated study results for all 41 evaluable patients will be presented at the annual meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Point Therapeutics Point Therapeutics Point Therapeutics Point Therapeutics