Phase 1 study (NCT04931823) of CPO100 (albumin bound docetaxel) in patients with advanced solid tumors.
Authors: Shepard Dale Randall , Kingsley Ed , Powderly John D. , LoRusso Patricia , Appleman Leonard Joseph , Spira Alexander I. , Rosen Lee S. , Grebenc Jessica , Ramirez Ana Arlene , Noldin Sydney , White Hannah , Sarker Erina , Behr Sarah , Griengo Janice , Lim Christopher , Arvay Lisa , Li Yejia , Novick Steven C. , Obara Grzegorz 
Published: June 2024

3027 Background: Docetaxel (Taxotere) is a widely used taxane; the use of docetaxel may have been limited by its original formulation, which contributes to multiple severe adverse effects. Polysorbate-80 in the current formulation has been implicated in several systemic reactions (e.g., hypersensitivity, nonallergic anaphylaxis, rash) and injection- and infusion-site adverse events (pain, erythema, thrombophlebitis). By eliminating polysorbate-80, the use of steroids at the time of infusion may also be eliminated. To improve the safety profile and enhance tumor-targeted drug exposure, CPO-100, an albumin-bound docetaxel formulation without polysorbate-80 was developed. This Phase 1 dose escalation study assessed the maximum tolerated dose (MTD), pharmacokinetics (PK), safety, and efficacy of CPO-100 administered without steroid pretreatment in a weekly schedule (3 weekly doses/ 1-week rest). Methods: Patients (pts) were enrolled in a modified 3 x 3 design starting at doses of 6 mg/m2 and ranging up to 50 mg/m2 on the weekly schedule (WS). At each visit, safety was assessed. PK data was collected on days 1, 8 and 15 of cycle 1. Efficacy was assessed every 2 cycles (8 weeks) until progression or treatment discontinuation. The MTD was determined with and without the use of granulocyte colony stimulating factor (GCSF) in cycle 1. Results: Thirty-four pts with various solid tumors were enrolled. Prior regimens: 2 to 17 (median 4). Prior exposure to taxanes: 18 pts (53%). The most common adverse events (AEs) were fatigue (N=19), nausea (N=18) and anemia (N=15). Grade 3/4 neutropenia (as a term or laboratory finding) for doses above 35 mg/m2 was 60%. Serious AEs (SAEs) occurred in 13 pts; SAEs regardless of relationship in more than 1 pt were pleural effusion, hypotension and pneumonia. For all evaluable pts, the overall response rate was 2/30 (7%) with two PRs observed in pts with breast and nasopharyngeal cancers. The disease control rate (DCR) was 60%. Among the 18 pts with SD or better, the median (K-M estimate) duration was approximately 10.9 months (mos; range 1.7 to 11.1 mos). A linear relationship between plasma concentrations of total docetaxel and dose was observed. The half-life of total docetaxel ranged from 13 to 39 hrs. Slight accumulation was observed on WS, and steady state was achieved after the second dose. Conclusions: Preliminary data with CPO-100 administered on a weekly basis shows potential efficacy in heavily pretreated pts, especially with prior taxane exposure, with a tolerable WS. With a similar dose, CPO-100 demonstrated a better safety profile than docetaxel. The most prominent concern is manageable neutropenia, especially on a dose above 35 mg/m2, where GCSF supplementation was needed. Further development is warranted, including combinations with agents such as PD-1/PD-L1 inhibitors that might benefit from absence of steroid prophylaxis. Clinical trial information: NCT04931823 .