SpringWorks Therapeutics (SWTX) "announced initial clinical data from the Phase 1/2 study evaluating nirogacestat, SpringWorks' investigational gamma secretase inhibitor, in combination with BLENREP, GSK plc's (GSK) antibody drug conjugate targeting B-cell maturation agent, in patients with relapsed or refractory multiple myeloma. In addition, SpringWorks also highlighted long-term follow-up data from a Phase 2 study sponsored by the National Cancer Institute evaluating nirogacestat in patients with progressing desmoid tumors, which included follow-up on progression-free survival and long-term safety data.2 These data sets will be shared in poster sessions at the 2022 American Society of Clinical Oncology Annual Meeting, June 3-7, 2022 in Chicago. The objective of this sub-study of GSK's DREAMM-5 platform trial is to determine if low-dose BLENREP in combination with nirogacestat results in similar efficacy with an improved ocular toxicity profile compared to single-agent BLENREP at its approved dose and schedule. The study opened with a dose-exploration arm evaluating 0.95 mg/kg BLENREP Q3W combined with 100 mg BID nirogacestat dosed continuously, and subsequently moved into a cohort expansion arm. The target enrollment for the CE arm of the study is 70 patients randomized either to BLENREP 2.5mg/kg Q3W monotherapy or low-dose BLENREP plus nirogacestat combination using the same dose as the DE arm cohort. The study enrolled patients with relapsed or refractory multiple myeloma who have received at least 3 prior lines of therapy, including an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody. The poster being presented at ASCO includes data from a total of 24 patients treated with low-dose BLENREP + nirogacestat across the DE and CE cohorts and 14 patients treated with monotherapy BLENREP in the CE cohort. At the time of the March 4, 2022 data cut-off, the median of follow-up in the low-dose BLENREP plus nirogacestat DE cohort was 34.5 weeks (5-88 weeks), with durations of response exceeding one year in some patients. Data from the CE cohorts are not yet mature with a median duration of follow-up of 12 weeks available at the time of data cut-off. The CE cohorts utilized the KVA ocular toxicity grading scale; Grade 3 ocular adverse events occurred in 1/14 patients in the low-dose BLENREP plus nirogacestat combination compared to 7/14 patients in the BLENREP monotherapy arm. The DE cohort utilized the CTCAE-5 ocular toxicity grading scale; the low-dose BLENREP plus nirogacestat combination demonstrated Grade 3 ocular adverse events in 2/10 patients. At the time of data cut-off, the objective response rate of low-dose BLENREP plus nirogacestat across the DE and CE cohorts was 38%, with 17% of patients achieving a VGPR or better. The ORR of the BLENREP monotherapy control arm was 50%, with no patients achieving a VGPR or better."