Phase I/Ii Study Of Gti-2040 Plus Docetaxel As 2nd-Line Treatment In Non-Small Cell Lung Cancer (Nsclc) And Other Solid Tumors.

7253 Background: Median survival in advanced NSCLC with systemic therapy is 8 to 10 months, with modest benefits from 1st-, 2nd-, and 3rd-line therapy. GTI-2040 (Lorus Therapeutics, Canada), an antisense oligonucleotide complementary to mRNA encoding the RNR R2 subunit, demonstrates preclinical activity against lung cancer cell lines, synergy with taxanes, and disease stabilization as a single agent in a phase I trial. Objective: To determine the recommended phase 2 dose (RP2D) of GTI-2040 plus docetaxel, and the objective response rate and toxicity at RP2D as 2nd-line therapy in advanced NSCLC. Methods: Advanced solid tumor (phase I) and NSCLC (phase II) patients (pts) with performance status 0–2, adequate renal, hepatic, and hematologic function, and ≤ 1 prior chemotherapy regimen were treated with escalating doses of GTI-2040 by 14-day continuous venous infusion (CVI) plus IV docetaxel on one day every 21 days. Pts in Phase II were treated at RP2D. Results: 18 pts have been treated, 11 at RP2D (7 NSCLC). Dose escalation is shown below, with GTI-2040 5 mg/kg by CVI for 14 days plus docetaxel 75 mg/m2 IV q21days as the RP2D. Dose-limiting toxicity was not seen in cycle 1 at any dose level. Toxicities included neutropenia, sepsis, fatigue, and GI toxicity. Pts received a median of 2 cycles at RP2D (1–7); 2 pts at RP2D developed grade 4 or 5 febrile neutropenia; 3 developed grade 3 thrombosis related to central venous catheters; 2 experienced grade 3 hyperglycemia (likely dexamethasone-related); 1 developed grade 3 anemia after cycle 2. Stable disease (SD) was seen in 10 (6 NSCLC, 2 prostate, 1 SCLC, 1 H&N), including 4 minor responses (3 NSCLC, 1 prostate) and 1 minor PSA response (prostate). 15 patients have come off treatment, 1 after 6 cycles, 7 for progressive disease (PD), 2 for toxicity (including toxic death), 3 at investigator discretion and 2 pts withdrew; 3 remain on treatment, 1 on cycle 7. Accrual, response, survival and toxicity will be updated. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis