SWTX - SpringWorks Therapeutics Announces Data to be Presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting | Benzinga
– Results from pivotal Phase 2b ReNeu trial of mirdametinib in patients with NF1-PN to be presented in an oral presentation –
– Additional data and analyses from Phase 3 DeFi trial of OGSIVEO® (nirogacestat) highlighting consistent safety and efficacy across subgroups of adults with desmoid tumors also being presented in oral and poster sessions –
STAMFORD, Conn., May 23, 2024 (GLOBE NEWSWIRE) -- SpringWorks Therapeutics, Inc. (NASDAQ:SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, today announced that four abstracts from the company's portfolio will be presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting being held May 31 to June 4, 2024.
Data from the pivotal Phase 2b ReNeu trial evaluating mirdametinib, an investigational MEK inhibitor, in adults and children with neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN) will be presented in an oral presentation. ReNeu is the largest multicenter trial conducted to date in patients with NF1-PN, a condition in which tumors can grow aggressively along peripheral nerves and lead to pain, disfigurement and other morbidities. In the ReNeu trial, mirdametinib treatment demonstrated deep and sustained tumor volume reductions, and improvement in pain and health-related quality of life across both the adult and pediatric cohorts.
In addition, three new data sets from the pivotal Phase 3 DeFi trial of nirogacestat in adults with desmoid tumors will be presented at ASCO. Monitoring ovarian function in oncology studies and the onset and resolution of ovarian toxicity for desmoid tumor patients treated with nirogacestat in the DeFi trial will be discussed in an oral presentation. Investigators will also present two posters that include post hoc analyses from the DeFi trial in high-risk patient populations, which reinforce the efficacy and safety of nirogacestat in adults with desmoid tumors across various clinical characteristics.
"We are very pleased to present important data at this year's ASCO annual meeting, including positive results from our pivotal Phase 2b ReNeu trial of mirdametinib in NF1-PN, which showed significant objective response rates confirmed by blinded independent central review, deep responses, as well as a manageable and tolerable safety profile in both adult and pediatric patients. These data are the foundation of our NDA, which we are on track to submit to the FDA by the end of the second quarter, and we believe provide compelling evidence of differentiation and potentially transformative benefit for patients with this devastating disease," said Jim Cassidy, M.D., Ph.D., Chief Medical Officer of SpringWorks. "In addition, new data and analyses from our Phase 3 DeFi trial further reinforce the robust efficacy and manageable safety profile of OGSIVEO across subgroups of adults with desmoid tumors who require systemic treatment."
Rapid Oral Presentations at the 2024 ASCO Annual Meeting
ReNeu: A pivotal phase 2b trial of mirdametinib in children and adults with neurofibromatosis type 1 (NF1)-associated symptomatic inoperable plexiform neurofibroma (PN)
Abstract #: 3016
Date and Time: June 3, 8:00 - 9:30 a.m. CDT (9:00 – 10:30 a.m. EDT)
As previously reported, results from the pivotal Phase 2b ReNeu trial (NCT03962543) demonstrated a statistically significant confirmed objective response rate (ORR), the primary endpoint of the study, as well as deep and sustained reduction in tumor volume and significant improvement in key secondary patient-reported outcome measures in both adults and children with NF1-PN. The data being presented at ASCO include:
- As of the data cutoff of September 20, 2023, mirdametinib treatment resulted in a confirmed ORR of 41% (24/58; P<0.001) in adults and 52% (29/56; P<0.001) in children, as assessed by blinded independent central review (BICR). Two additional adult patients and one additional pediatric patient had a confirmed partial response in the long-term follow-up phase.
- Tumor volume reductions were deep and durable over the course of the study. Median (range) best change in tumor volume from baseline was -41% (-90% to 13%) in adults and -42% (-91% to 48%) in children. Among study participants with a confirmed objective response on mirdametinib, 62% of adults and 52% of children achieved a >50% reduction in tumor volume.
- The median treatment duration for both adults and children was 22 months; the median (range) time to onset of response was 7.8 months (4 to 19 months) in adult patients and 7.9 months (4 to 19 months) in pediatric patients; the median duration of response was not reached in either group.
- Both adult and pediatric patients experienced improvement in patient-reported pain and patient-reported (adult) or patient- or parent proxy-reported (children) health-related quality of life (HRQoL) at the pre-specified Cycle 13 assessment. Least square (LS) mean change from baseline at Cycle 13 in worst tumor pain (assessed by Numeric Rating Scale-11) was -1.3 (P<0.001) in adults and -0.8 (P=0.003) in children. LS mean change from baseline at Cycle 13 in HRQoL was 3.9 in adults (P=0.018) and 4.0 (P=0.096) as self-reported in children; parent-proxy reported LS mean change in HRQoL in children was 5.6 (P=0.005).
- Mirdametinib was generally well tolerated in the ReNeu trial, with most adverse events (AEs) being Grade 1 or 2. Among all study participants, 21% of adults and 9% of children discontinued the study due to treatment-related adverse events (TRAEs), and dose reductions due to TRAEs were 17% in adults and 12% in children.
- The most frequently reported TRAEs affecting >20% of adult participants were dermatitis acneiform, diarrhea, nausea, vomiting, and fatigue. The most frequently reported TRAEs affecting ?20% of pediatric participants were dermatitis acneiform, diarrhea, paronychia (infection of the tissue adjacent to a fingernail or toenail), nausea, decrease in ejection fraction (asymptomatic), and increase in blood creatinine phosphokinase (asymptomatic).
"ReNeu is the largest multicenter NF1-PN trial conducted to date and prospectively used blinded independent central review to confirm target tumor response in NF1-PN patients," said Christopher L. Moertel, M.D., Medical Director of the Pediatric Neuro-Oncology and Neurofibromatosis Program and Kenneth and Betty Jayne Dahlberg Professor of Pediatrics at the University of Minnesota School of Medicine and lead investigator of the ReNeu trial. "The potentially unprecedented depth of response and significant reduction in pain and other quality of life measures across the pediatric and adult cohorts in the ReNeu study, coupled with the manageable safety profile, support the potential for mirdametinib to become an important and much needed treatment for patients with NF1-PN, particularly adults who currently do not have an approved treatment option."
Monitoring ovarian function in oncology trials: Results and insights from the DeFi phase 3 trial of nirogacestat in desmoid tumor
Abstract #: 11520
Date and Time: May 31, 2:45 - 4:15 p.m. CDT (3:45 – 5:15 p.m. EDT)
Results and insights from the DeFi trial (NCT03785964) on monitoring ovarian function in oncology studies will be presented at ASCO. In the DeFi trial, ovarian toxicity (OT) was reported in 75% (27 of 36) of females of reproductive potential (FORP) receiving nirogacestat and 0% (0 of 37) of FORP patients receiving placebo. In a post hoc analysis, resolution of OT was reported by investigators in 78% (21 of 27) of FORP patients, assessed by reproductive hormone values (FSH, LH, AMH, progesterone and estradiol) or perimenopausal symptoms (e.g., menstrual irregularity) or both. Investigators reported OT resolution among all patients (11/11) who were off treatment for any reason, with a median time to resolution of 76 days. Among patients who remained on nirogacestat, 71% (10/14) of patients experienced resolution of OT according to investigators, with a median time to resolution of 171 days.
"Historically, ovarian toxicity has rarely been systematically assessed in cancer clinical trials. And when collected, data have not always been gathered with the goal of counseling future patients clearly in mind. The DeFi trial developed one of the most comprehensive assessments of ovarian function in an oncology clinical trial to date. This timely and important ASCO presentation will review best practices for evaluating a drug's effect on ovarian function for future cancer trials, using the DeFi trial as an example," said Elizabeth Loggers, M.D., Ph.D., Associate Professor, Clinical Research Division, sarcoma expert and Medical Director, Supportive and Palliative Care, Fred Hutchinson Cancer ...