SpringWorks Therapeutics to Present Data at 2024 ASCO Annual Meeting

SpringWorks Therapeutics Inc., a company dedicated to addressing severe rare diseases and cancer, recently announced that four abstracts from its portfolio will be presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. The event, taking place from May 31 to June 4, 2024, will feature significant findings from the pivotal Phase 2b ReNeu trial of mirdametinib in patients with neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN) and the Phase 3 DeFi trial of nirogacestat in adults with desmoid tumors.

The Phase 2b ReNeu trial, the largest multicenter study for NF1-PN to date, demonstrated that mirdametinib, an investigational MEK inhibitor, provided profound and lasting tumor volume reductions and improved pain and health-related quality of life in both adult and pediatric patients. The trial showed a confirmed objective response rate (ORR) of 41% in adults and 52% in children, with a substantial percentage achieving more than a 50% reduction in tumor volume.

In terms of safety, mirdametinib was generally well tolerated, with most adverse events being mild to moderate. Dermatitis acneiform, diarrhea, and nausea were among the most common treatment-related adverse events (TRAEs). Despite some discontinuations and dose reductions due to TRAEs, the overall safety profile was considered manageable.

The Phase 3 DeFi trial of nirogacestat, focusing on desmoid tumors, also presented compelling data. An oral presentation will discuss the monitoring of ovarian function and the occurrence of ovarian toxicity in patients treated with nirogacestat. Notably, ovarian toxicity was reported in 75% of females of reproductive potential receiving nirogacestat, but investigators observed a 78% resolution rate in these cases, emphasizing the importance of comprehensive monitoring in oncology trials.

Additional analyses from the DeFi trial evaluated the efficacy of nirogacestat in subgroups of patients with poor prognostic factors and those with adenomatous polyposis coli (APC) mutations. These analyses revealed consistent improvements in progression-free survival (PFS) and ORR, even in patients with historically poor prognoses. The results reinforce the potential of nirogacestat to deliver clinically meaningful benefits across diverse patient populations.

The ReNeu trial (NCT03962543) enrolled 114 patients to receive mirdametinib, administered orally, at a dose of 2 mg/m² twice daily in a 3-week on, 1-week off dosing schedule. The primary endpoint was achieving a ≥ 20% reduction in target tumor volume, confirmed by MRI. Secondary endpoints included overall safety, duration of response, and changes in patient-reported outcomes.

Neurofibromatosis type 1 (NF1) is a rare genetic condition caused by mutations in the NF1 gene, affecting an estimated 100,000 individuals in the United States. Patients with NF1 face a wide range of symptoms, including tumor growth, which can lead to significant morbidity and reduced life expectancy. NF1-PNs, which affect about 30-50% of NF1 patients, are challenging to manage surgically and often require innovative therapeutic approaches like MEK inhibitors.

Mirdametinib, a potent oral MEK inhibitor, is being developed for NF1-PN and other conditions. The drug has received Orphan Drug designation from both the FDA and the European Commission, along with Fast Track designation and Rare Pediatric Disease designation from the FDA.

On the other hand, the DeFi trial (NCT03785964) is a global, randomized Phase 3 study assessing the efficacy of nirogacestat in adult patients with desmoid tumors. The trial’s primary endpoint is progression-free survival, with secondary endpoints including objective response rate and changes in tumor volume and patient-reported outcomes.

Desmoid tumors are rare, non-metastasizing but aggressive soft tissue tumors that can significantly affect quality of life and, in rare cases, be life-threatening. Current treatment guidelines recommend systemic therapies over surgical interventions due to high recurrence rates following surgery.

Nirogacestat, branded as OGSIVEO®, is approved in the United States for treating adult patients with progressing desmoid tumors requiring systemic treatment. The drug is also being investigated for other indications, including ovarian granulosa cell tumors and multiple myeloma.

SpringWorks Therapeutics, leveraging a precision medicine approach, aims to deliver transformative treatments for severe rare diseases and cancer. The company’s diversified portfolio includes targeted therapies for various cancers, spanning from preclinical development to advanced clinical trials. Through partnerships with industry and academic leaders, SpringWorks is committed to expanding its impact and offering more solutions for patients in need.