Abstract
RTOG 3508/AbbVie M13-813/INTELLANCE-1 was a phase 3 trial of depatuximab-mafodotin (depatux-m, formerly ABT-414) that accrued 639 patients with EGFR-amplified newly diagnosed GBM. At the pre-specified interim OS analysis, the futility criteria were met and there was no survival benefit from adding depatux-m to SOC. Pre-specified secondary NCF analyses included time to decline in verbal learning and memory as assessed by the HVLT-R Total Recall based on the reliable change index. Exploratory NCF analyses examined changes in other HVLT-R outcomes over time. As corneal epitheliopathy causing visual impairment is a known toxicity of depatux-m, NCF tests that did not depend on visual acuity were employed. NCF testing occurred at baseline, day 1 of the first cycle of adjuvant depatux-m, every other cycle (i.e., 8 weeks) thereafter, and at progression. Compliance with test completion was 95% at screening and 80%, 70%, 58%, 51%, 47% thereafter through cycle 9. The most common reasons for missing data was site error. Time to HVLT-R Total Recall decline trended worse in the depatux-m arm compared to placebo but the difference was not significant (12 month deterioration: 41.2%, 95% CI: 3.50–47.2 vs 32.4%, 95% CI: 26.6- 38.4, p=0.052). The depatux-m arm, in comparison to the placebo arm, showed greater decline from baseline on the HVLT-R at the following time points: cycle 3 (Total Recall: mean= -1.8, SD=5.7 vs mean= -0.5, SD=5.5, respectively, p=0.046; Delayed Recall: mean= -1.1, SD=3.0 vs. mean= -0.2, SD=2.7, respectively, p=0.01), cycle 7 (Total Recall: mean= -0.6, SD=5.1 vs mean= 1.4, SD=5.0, respectively, p=0.009; Delayed Recall: mean -0.6, SD=3.0 vs. mean= 0.5, SD=2.7, respectively, p=0.01), and cycle 9 (Delayed Recall: mean=-0.4, SD=2.7 vs. mean= 0.8, SD=2.4, respectively, p=0.003). Depatux-m added to concurrent chemoradiation and adjuvant temozolomide was associated with faster time to deterioration and worse episodic learning and memory over time than placebo.
Predictors Of Utility Over Time Among Patients With Treatment-Naïve Advanced Melanoma From The Phase 3 Checkmate 066 Trial
