FDA Grants Orphan Drug Designation to Rucosopasem for Pancreatic Cancer

May 18, 2023

The FDA has granted an orphan drug designation to rucosopasem manganese for the treatment of patients with pancreatic cancer.

The FDA has granted an orphan drug designation to rucosopasem manganese (GC4711) for the treatment of patients with pancreatic cancer, according to an announcement from Galera Therapeutics.¹

Rucosopasem is a next-generation selective dismutase mimetic being evaluated to improve the activity of stereotactic body radiation therapy (SBRT) in patients with pancreatic cancer and lung cancer. The agent is under study in the randomized phase 1/2 GRECO-1 (NCT04476797) and phase 2b GRECO-2 (NCT04698915) trials in combination with SBRT in patients with non–small cell lung cancer (NSCLC) and locally advanced pancreatic cancer, respectively.^2,3

“Orphan drug designation for rucosopasem highlights the urgent need for more treatment options to extend survival in patients with pancreatic cancer, which is the fourth-leading cause of cancer death in the U.S.,” Mel Sorensen, MD, president and chief executive officer of Galera, said in a press release. “Following our announcement of encouraging survival results from our pilot proof-of-concept trial in patients with locally advanced pancreatic cancer in 2021, we initiated the GRECO-2 trial, which is currently enrolling. We believe rucosopasem has the potential to improve the efficacy of SBRT for pancreatic cancer, and we anticipate topline data from GRECO-2 by the end of [2024].”

To be eligible for enrollment in GRECO-1, patients must be referred for SBRT with large peripheral lesions (>1cm to 7cm) and/or have central localized, node-negative, nonmetastatic NSCLC, with an ECOG performance status no greater than 3. Feasibility of SBRT will be determined by the treating physician.

In the study, SBRT will be administered to the tumor at a dose of or 3 fractions of between 18 Gy and 20 Gy or 5 fractions of between 10 Gy and 12 Gy. SBRT fractions will be administered within 180 minutes after rucosopasem or placebo infusion.

Following completion of the phase 1 portion, approximately 66 patients with early-stage large and/or central localized NSCLC will be enrolled to the randomized, placebo-controlled phase 2 portion of the study, where they will receive GC4711 or placebo given intravenously (IV) over 15 minutes before each fraction of SBRT, beginning the day of the first fraction of SBRT and ending the last day of SBRT.

Patients will be evaluated for treatment-emergent adverse effects (AEs) for 30 days after SBRT completion. Additionally, patients will undergo long-term safety evaluation for all acute AEs at 90 days post-SBRT and at 1 year post-SBRT for late-onset toxicities.

In-field tumor response and overall survival (OS) will be assessed through 24 months after SBRT completion.

The primary objective will determine the number of dose-limiting toxicities during treatment and within 30 days of completing SBRT. The percent of patients with a best RECIST response of complete response or partial response through month 6 will serve as a secondary objective measure.

In GRECO-2, eligible patients must have histologically or biopsy-proven adenocarcinoma of the pancreas. Cytology can suffice in the absence of histologic confirmation. Patients with newly diagnosed nonmetastatic pancreatic cancer must be deemed eligible to receive SBRT by a tumor board and have completed at least 6 weeks of chemotherapy consisting of FOLFIRINOX, modified FOLFIRINOX, or a gemcitabine-based doublet regimen prior to initiating SBRT.

Additionally, patients must show confirmation of nonmetastatic disease via CT scan at screening, have an ECOG performance status between 0 and 2, and have adequate end-organ function.

Patients are being randomly assigned to receive rucosopasem or placebo as a 15-minute infusion plus SBRT.

Median OS and progression-free survival from the point of SBRT completion will serve as the primary and secondary end points of the study, respectively.

References

Galera announces FDA orphan drug designation granted to rucosopasem for pancreatic cancer. News release. May 18, 2023. Accessed May 18, 2023. https://investors.galeratx.com/news-releases/news-release-details/
Phase I/II study of SBRT and GC4711 for centrally located or large NSCLC (GRECO-1). ClinicalTrials.gov. Updated February 8, 2023. Accessed May 18, 2023. https://clinicaltrials.gov/ct2/show/NCT04476797
Phase 2b study of GC4711 in combination with SBRT for nonmetastatic pancreatic cancer. ClinicalTrials.gov. Updated May 18, 2023. Accessed May 18, 2023. https://clinicaltrials.gov/ct2/show/NCT04698915