Abstract
Background
Approved therapies for R/M ACC are lacking. Notch mutations (Notchmut) are found in ∼20% of ACC and are linked to aggressive disease and poor prognosis. AL101 is a gamma-secretase inhibitor that blocks Notch signaling, which is being prospectively studied in this biomarker driven high-risk population.
Methods
ACCURACY is a phase 2, multicenter, open-label study of AL101 (4 or 6 mg IV QW) in patients (pts) with R/M ACC and Notch1-4mut with evidence of disease progression. The primary endpoint was investigator-assessed objective response rate (ORR) by RECIST v1.1 (or modified MDACC bone criteria). A benchmark for the ACCURACY results was developed from a meta-analysis of outcomes among R/M ACC pts (regardless of Notch status) treated in other clinical trials.
Results
ACCURACY enrolled 87 pts with median age 50 and 59 years in the 4 mg and 6 mg arms, respectively. Prior systemic therapy was used in 60% of 4 mg and 51% of 6 mg pts. As of the data cutoff of 27 Oct 2022, among 77 evaluable pts, ORRs of 14.6% for 4 mg and 8.3% for 6 mg compared favorably with ORRs from the meta-analysis (Table). The most common treatment-related adverse events (TRAE) for pooled doses were diarrhea (70%), fatigue (51%), nausea (47%), hypophosphatemia (38%), vomiting (28%), and cough (25%). Grade 3 and 4 TRAE occurred in 35 (40%) and 2 (2%) pts, respectively. TRAE led to discontinuation of AL101 in 6 (7%) pts (3 on 4 mg and 3 on 6 mg) and 2 (2%) deaths (pneumonia and acute respiratory syndrome).
Approved therapies for R/M ACC are lacking. Notch mutations (Notchmut) are found in ∼20% of ACC and are linked to aggressive disease and poor prognosis. AL101 is a gamma-secretase inhibitor that blocks Notch signaling, which is being prospectively studied in this biomarker driven high-risk population.
Methods
ACCURACY is a phase 2, multicenter, open-label study of AL101 (4 or 6 mg IV QW) in patients (pts) with R/M ACC and Notch1-4mut with evidence of disease progression. The primary endpoint was investigator-assessed objective response rate (ORR) by RECIST v1.1 (or modified MDACC bone criteria). A benchmark for the ACCURACY results was developed from a meta-analysis of outcomes among R/M ACC pts (regardless of Notch status) treated in other clinical trials.
Results
ACCURACY enrolled 87 pts with median age 50 and 59 years in the 4 mg and 6 mg arms, respectively. Prior systemic therapy was used in 60% of 4 mg and 51% of 6 mg pts. As of the data cutoff of 27 Oct 2022, among 77 evaluable pts, ORRs of 14.6% for 4 mg and 8.3% for 6 mg compared favorably with ORRs from the meta-analysis (Table). The most common treatment-related adverse events (TRAE) for pooled doses were diarrhea (70%), fatigue (51%), nausea (47%), hypophosphatemia (38%), vomiting (28%), and cough (25%). Grade 3 and 4 TRAE occurred in 35 (40%) and 2 (2%) pts, respectively. TRAE led to discontinuation of AL101 in 6 (7%) pts (3 on 4 mg and 3 on 6 mg) and 2 (2%) deaths (pneumonia and acute respiratory syndrome).
| Original language | English |
|---|---|
| Journal | Annals of oncology : official journal of the European Society for Medical Oncology / ESMO |
| Volume | 34 |
| Issue number | 2 |
| Publication status | Published - Oct 2023 |
