A phase 1 dose escalation/expansion study of FID-007, a novel nanoparticle paclitaxel formulation, in patients with solid tumors.
Authors: Thomas Jacob Stephen , Habib Diane , Hanna Diana L. , Nakhoul Christina Linda Antoine , Martynova Anastasia , Iqbal Syma , Nieva Jorge J. , Tsao-Wei Denice D. , Hsieh Ming , Yin Ray , El-Khoueiry Anthony B. 
Published: June 2023

3026 Background: FID-007 (FID) consists of paclitaxel encapsulated in a polyethyloxazoline (PEOX) polymer excipient designed to enhance PK, biodistribution, and tolerability. In addition to allowing the drug to remain in solution until it can enter a cancer cell, the PEOX nanoparticle preferentially delivers paclitaxel to the tumor through the leaky hyperpermeable vasculature. In xenograft studies, FID reduced or limited tumor growth in multiple tumor types including lung, gastric, breast, pancreatic, and ovarian cancer. Preclinically, FID was more effective at lower or comparable taxane doses, including nab-paclitaxel, with fewer side effects. We present the first-in-human trial of FID. Methods: The study is evaluating the safety, PK, and efficacy of FID in pts with advanced solid tumors. The primary objective is to determine the MTD and RP2D. Pts received FID in doses between 15mg/m2 and 160mg/m2 using a standard 3+3 dose escalation design. FID was given IV on Days 1, 8, and 15 of a 28-day cycle. Eligibility included ECOG 0-2, adequate organ function, and ≤ 3 prior lines of cytotoxic therapy for advanced disease. Results: Thirty-six patients were treated across 7 dose levels. Median age was 61 (39-65). ECOG PS was 2 in 1 patient, 1 in 69% of patients. Median number of prior therapies was 2 (1-5). Median number of cycles was 2.5 (1-30). There were 2 DLTs of grade 3 rash at 100 mg/m2. Given the transient nature of the rash and response to topical therapy, DLT definition was modified to exclude grade 3 rash that lasts ≤ 7 days and 3 additional patients were treated at 100 mg/m2 which was deemed tolerable. There was 1 DLT of grade 4 WBC decrease at 125 mg/m2, and 1 DLT of G3 febrile neutropenia at 160 mg/m2. There was no MTD. All grade treatment related adverse events (TRAEs) in ≥ 25% of pts were rash (64%), alopecia (56%), leukopenia (47%), pruritus (44%), neutropenia (42%), anemia (42%), fatigue (39%), nausea (33%), anorexia (31%), dysgeusia (25%) and peripheral sensory neuropathy (25%). Grade 3/4 TRAEs occurring in >1 pt were maculopapular rash (25%), anemia, neutropenia, and leukopenia (17% each). Of 36 evaluable patients, 7 (19%) had a partial response by RECIST 1.1 (pancreatic, biliary tract, and HNSCC) and 13 (36%) had stable disease. Three out of 4 HNSCC patients with PR had previously been treated with docetaxel. PK is linear and dose proportional. There is no paclitaxel accumulation after weekly dosing, and t1/2 is between 18-26 hours. Based on overall tolerability and PK, the dose of 125mg/m2 (dose level 6) has been chosen as RP2D. Conclusions: FID has a manageable safety profile and demonstrates preliminary evidence of anti-tumor activity in heavily pre-treated pts across different tumor types. No high-grade neuropathy has been noted to date. RP2D of FID is set at 125mg/m2. PK is linear, dose proportional and comparable to that of nab-paclitaxel. Clinical trial information: NCT03537690 .