Phase 1 study (NCT04931823) of CPO100 (albumin bound docetaxel) in patients with advanced solid tumors.
Authors: Dale Randall Shepard, Ed Kingsley, John D. Powderly, Patricia LoRusso, Leonard Joseph Appleman, Alexander I. Spira, Lee S. Rosen, Jessica Grebenc, Ana Arlene Ramirez, Sydney Noldin, Hannah White, Erina Sarker, Sarah Behr, Janice Griengo, Christopher Lim, Lisa Arvay, Yejia Li, Steven C. Novick, Grzegorz Obara
Journal: Journal of Clinical Oncology (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/m 2 and ranging up to 50 mg/m 2 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/m 2 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/m 2 , 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 .