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POTELIGEO(mogamulizumab-kpkc)injection,forintravenous(十)
EO arm, baseline CCR4expression status by immunohistochemistry was available in 140 patients (75%), of whom allhad CCR4 detected on ≥1% of lymphocytes on skin biopsy, and 134/140 (96%) had CCR4detected on ≥10% of the lymphocytes. CCR4 expression status was similar in the vorinostat arm.
During randomized treatment, the median duration of exposure to POTELIGEO was 5.6 months(range: <1 to 45.3 months), with 48% of patients with at least 6 months of exposure and 23%with at least 12 months of exposure. The median duration of exposure to vorinostat was 2.8months (range: <1 to 34.8 months), with 22% of patients with at least 6 months of exposure.
Efficacy was based on investigator-assessed progression-free survival (PFS), which was definedas the time from the date of randomization until documented progression of disease or death.
Other efficacy measures included overall response rate (ORR) based on global compositeresponse criteria that combine measures from each disease compartment (skin, blood, lymphnodes and viscera). Responses required confirmation at two successive disease assessments,which included the modified Severity Weighted Assessment Tool, skin photographs, central flowcytometry, and computed tomography.
The trial demonstrated that POTELIGEO significantly prolonged PFS compared to vorinostat(Table 3). The Kaplan-Meier curve for PFS by Investigator is shown in Figure 1. The estimatedmedian follow-up for investigator-assessed PFS was 13 months in the POTELIGEO arm and10.4 months in the vorinostat arm. By independent review committee assessment, the estimatedmedian PFS was 6.7 months (95% CI, 5.6 to 9.4) in the POTELIGEO arm and 3.8 months (95%CI, 3.0 to 4.7) in the vorinostat arm (hazard ratio 0.64; 95% CI: 0.49, 0.84).Figure 1 Kaplan-Meier Curve for Progression-Free Survival per Investigator
Table 3 also summarizes investigator-assessed confirmed response rates, overall and by diseasecompartment. The trial demonstrated improvement in ORR with POTELIGEO.
Table 3 Efficacy of Randomized Treatment (Trial 1)
Outcome per Investigator POTELIGEO
N=186
Vorinostat
N=186
PFS
Number of events, n 110 131
Progressive disease 104 128
Death 6 3
Median PFS (95% CI) (months) a
7.6 (5.6, 10.2) 3.1 (2.8, 4.0)
Hazard ratio (95% CI)
Log rank p-value
0.53 (0.41, 0.69)
<.001
Overall response rate
(confirmed CR + PR), n (%) b, c
52 (28) 9 (5)
95% CI (22, 35) (2, 9)
P-value d
<.001
Duration of overall response (months)
Median (95% CI) a
13.9 (9.3, 18.9) 9.0 (4.6, NE)
Confirmed best overall response b
CR, n (%) 4 (2) 0 (0)
95% CI (1, 5) (0, 2)
PR, n (%) 47 (25) 9 (5)
95% CI (20, 33) (2, 9)
Response by compartment (confirmed CR + PR) c
Blood n=124 n=125
Response rate, n (%) 83 (67) 23 (18)
95% CI (58, 75) (12, 26)
Skin n=186 n=186
Response rate, n (%) 78 (42) 29 (16)
95% CI (35, 49) (11, 22)
Lymph nodes n=136 n=133
Response rate, n (%) 21 (15) 5 (4)
95% CI (10, 23) (1, 9)
Viscera n=6 n=4
Response rate, n (%) 0 (0) 0 (0)
95% CI (0, 46) (0, 60)
a Kaplan-Meier estimate.
b
Based on Global Composite Response score.
c Responses in blood and skin must have persisted for at least 4 weeks to be considered confirmed and were eva luated every
4 weeks for the first year. Responses in lymph nodes, visceral disease and overall were eva luated every 8 weeks for the first
year.
d
From Cochran-Mantel-Haenszel test adjusted for disease type, stage, and region.
CI=confidence interval; CR=comp |
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