J. Yang, M. C. Palanca-Wessels, Y. Wang, N. Josephson, S. L. Peng; Seattle Genetics, Inc., Bothell, WAINTRODUCTION:
Brentuximab vedotin (BV) is a CD30-directed antibody drug conjugate (ADC) including a protease-cleavable linker attached to a microtubule-disrupting agent, monomethyl auristatin E (MMAE). BV has demonstrated robust antitumor activity and acceptable toxicity in Hodgkin lymphoma (HL) patients aged <60 with similar tumor responses and tolerability in patients ≥60 yrs.METHODS:
In an ongoing Phase II study, treatment-naïve HL patients aged ≥60 yrs received BV 1.8 mg/kg Q3W. Pharmacokinetic (PK) parameters of ADC and MMAE during Cycle 1 were estimated by non-compartmental analysis and compared to previously completed Phase I DDI study in CD30+ hematological malignancies patients treated with 1.8 mg/kg BV only.RESULTS:
Preliminary overall PK parameters of BV are summarized in the Table and were similar to those seen in the DDI study. Additional analyses of the present study showed that ADC and MMAE exposures in subjects aged ≥ 60 and <75 yrs were comparable to those ≥75 yrs and exposures in subjects with mild (CrCL: >50 to ≤80 mL/min) and moderate (CrCL:≥30 to ≤50 mL/min ) renal impairment appeared comparable to subjects with normal (CrCL: >80 mL/min) renal function.
|Ph 2 (Age ≥60 yrs)||Ph 1 DDI Study w/o interacting drug|
|Age||Median (n, range).||78 (26, 64 – 92)||39 (14, 16 - 68)|
|Parameters||Geometric mean (n, CV%)||Geometric mean (n, CV%)|
|ADC||AUCa(µg•day/mL)||Geometric mean (n, CV%)||103 (20, 19.8)||89.8 (11, 25)|
|Ceoi (µg/mL)||Geometric mean (n, CV%)||44.4 (23, 28.0)||36.7 (11, 34)|
|MMAE||AUCa (ng•day/mL)||Geometric mean (n, CV%)||35.5 (16, 64.4)||40.1 (14, 53)|
|Cmax (ng/mL)||Geometric mean (n, CV%)||5.06 (23, 65.4)||4.98 (14, 67)|
|Tmax (day)||Median (n, range).||1.95 (23, 0.87 - 7.05)||3.00 (14, 0.99-5.01)|
for Phase II study and AUC0-inf
for Phase I studyCONCLUSION:
Based on current data, there do not appear to be significant age-related changes in the PK of BV in adults.