Table 4 Summary of Cycle 1 PK analyses.

From: PARP inhibition with rucaparib alone followed by combination with atezolizumab: Phase Ib COUPLET clinical study in advanced gynaecological and triple-negative breast cancers

Parameter

Part 1 (dose finding)

Part 2 (dose expansion)

Cohort 1

Cohort 2

Ovarian cancer

TNBC, Arm C

Arm A (tBRCAmut)

Arm B (tBRCAwt/LOHhigh)

Atezolizumab Cycle 1 arithmetic mean (CV)

Sparse PK sampling

Sparse PK sampling

Cmax, μg/mL

(n = 3) 429 (7.0)

(n = 6) 500 (19.4)

(n = 10) 469 (18.8)

(n = 4) 438 (9.4)

(n = 4) 425 (35.3)

Cmin, μg/mL

(n = 3) 84.3 (32.0)

(n = 5) 96.0 (23.8)

(n = 10) 77.2 (22.1)

(n = 4) 95.7 (17.9)

(n = 4) 98.7 (26.3)

Rucaparib arithmetic mean (CV)

Intensive PK sampling

Sparse PK sampling after 21-day run-in

Cmax, ng/mL

(n = 2) 2270 (27.4)

(n = 6) 3185 (46.8)

–

–

_

Cmin, ng/mL

(n = 2) 1730 (28.6)

(n = 6) 2650 (28.9)

(n = 9) 1910 (88.7)

(n = 4) 1500 (75.7)

(n = 5) 1180 (52.5)

AUClast (h·ng/mL)

(n = 2) 15 072 (21.2)

(n = 6) 22 082 (41.6)

–

–

–

  1. AUClast area under the concentration–time curve to the last measurable plasma concentration, Cmax maximum concentration observed, Cmin minimum concentration during the dosing interval or trough concentration, CV coefficient of variation, LOH loss of heterozygosity, mut mutated, PK pharmacokinetic, tBRCA tumour BRCA gene, TNBC triple-negative breast cancer, wt wild type.
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