TY - JOUR
T1 - First‐in‐human, phase I/IIa study of CRLX301, a nanoparticle drug conjugate containing docetaxel, in patients with advanced or metastatic solid malignancies
AU - Piha-Paul, S.A.
AU - Thein, K.Z.
AU - De Souza, P
AU - Kefford, R.
AU - Gangadhar, T.
AU - Smith, C.
AU - Schuster, S.
AU - Zamboni, W.C.
AU - Dees, C.E.
AU - Markman, B.
PY - 2021
Y1 - 2021
N2 - Background This was a phase I/IIa study to investigate the tolerability, efficacy and pharmacokinetics (PK)/ pharmacodynamics (PD) of CRLX301, CDP-based nanoparticle formulation of docetaxel.ÃÂ MethodsÃÂ The study was conducted in two parts. In part 1, dose-escalation using a standard 3 + 3 design was performed in two dosing schedules (every week (QW) and every 3 weeks (Q3W)). Part 2 was comprised of a dose expansion at 75ÃÂ mg/m2 Q3W. PK studies were performed on both dosing schedules.ÃÂ ResultsÃÂ Forty-two patients were recruited onto the study with a median age of 64(range 38–76); median number of prior systemic therapies was 5(range 0–10). Grade 3/4 treatment-related toxicities included: neutropenia (21.4 %), infusion related reaction (11.9 %), anemia (7.1 %), fatigue (4.8 %), diarrhea (4.8 %), and peripheral neuropathy (4.8 %). The maximum tolerated dose was 75ÃÂ mg/m2 given on the Q3W schedule and was not determined on the QW schedule. In this heavily pre-treated population, four patients (12.9 %) achieved stable disease (SD) ≥ 4 months and 2 patients (6.5 %) achieved partial response (PR) for a clinical benefit rate (CBR) of 19.4 % (6/31 patients). The PRs were seen in prostate and breast adenocarcinoma (one each). CRLX301 exhibited some PK advantages over docetaxel including higher retention of drug in plasma, slower clearance and controlled slow release of docetaxel from the carrier.ÃÂ ConclusionsÃÂ In this heavily pretreated patient population, the safety profile was acceptable for CRLX301 therapy. There was some evidence of preliminary tumor efficacy, but further work is necessary to find the optimal dose and schedule of this formulation. Clinicaltrials.gov trial registration number: NCT02380677 (Date of registration: March 2, 2015).
AB - Background This was a phase I/IIa study to investigate the tolerability, efficacy and pharmacokinetics (PK)/ pharmacodynamics (PD) of CRLX301, CDP-based nanoparticle formulation of docetaxel.ÃÂ MethodsÃÂ The study was conducted in two parts. In part 1, dose-escalation using a standard 3 + 3 design was performed in two dosing schedules (every week (QW) and every 3 weeks (Q3W)). Part 2 was comprised of a dose expansion at 75ÃÂ mg/m2 Q3W. PK studies were performed on both dosing schedules.ÃÂ ResultsÃÂ Forty-two patients were recruited onto the study with a median age of 64(range 38–76); median number of prior systemic therapies was 5(range 0–10). Grade 3/4 treatment-related toxicities included: neutropenia (21.4 %), infusion related reaction (11.9 %), anemia (7.1 %), fatigue (4.8 %), diarrhea (4.8 %), and peripheral neuropathy (4.8 %). The maximum tolerated dose was 75ÃÂ mg/m2 given on the Q3W schedule and was not determined on the QW schedule. In this heavily pre-treated population, four patients (12.9 %) achieved stable disease (SD) ≥ 4 months and 2 patients (6.5 %) achieved partial response (PR) for a clinical benefit rate (CBR) of 19.4 % (6/31 patients). The PRs were seen in prostate and breast adenocarcinoma (one each). CRLX301 exhibited some PK advantages over docetaxel including higher retention of drug in plasma, slower clearance and controlled slow release of docetaxel from the carrier.ÃÂ ConclusionsÃÂ In this heavily pretreated patient population, the safety profile was acceptable for CRLX301 therapy. There was some evidence of preliminary tumor efficacy, but further work is necessary to find the optimal dose and schedule of this formulation. Clinicaltrials.gov trial registration number: NCT02380677 (Date of registration: March 2, 2015).
UR - https://hdl.handle.net/1959.7/uws:66362
U2 - 10.1007/s10637-021-01081-x
DO - 10.1007/s10637-021-01081-x
M3 - Article
SN - 0167-6997
VL - 39
SP - 1047
EP - 1056
JO - Investigational New Drugs
JF - Investigational New Drugs
IS - 4
ER -