FDA Grants Orphan Drug Designation to Rucosopasem for Pancreatic Cancer

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

Rucosopasem is a next-generation selective dismutase mimetic which is in development to improve the activity of stereotactic body radiation therapy (SBRT) in patients with pancreatic cancer and lung cancer.

Currently, the agent is being assessed in 2 trials, the randomized phase 1/2 GRECO-1 (NCT04476797) and phase 2b GRECO-2 (NCT04698915) trials, in combination with SBRT for the treatment of patients with non–small cell lung cancer (NSCLC) and locally advanced pancreatic cancer.^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 [United States].,” said Mel Sorensen, MD, president and chief executive officer of Galera, 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].”

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For the GRECO-1 study, patients aged 18 years and older are eligible to enroll in the trial if they have central localized, node-negative, nonmetastatic NSCLC and/or are referred for SBRT with large peripheral lesions (>1cm to 7cm), have an ECOG performance status of 0-3, and have adequate end-organ function.² The treating physician will determine the feasibility of SBRT.

Once enrolled, patients will be given SBRT 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 following rucosopasem or placebo infusion.

Once the phase 1 portion of the study is completed, 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. Here, patients will receive either GC4711 or placebo given via intravenous (IV) infusion for 15 minutes prior to each fraction of SBRT. This will begin the day of the first fraction of SBRT and end the last day of SBRT. Those enrolled will be evaluated for treatment-emergent adverse effects (AEs) for 30 days after SBRT completion, and patients will undergo long-term safety evaluation for all acute AEs at 90 days post-SBRT, as well as at 1 year post-SBRT for late-onset toxicities. Additionally, in-field tumor response and overall survival (OS) will be assessed through 24 months after SBRT completion.

The primary end points of the study are to determine the number of dose-limiting toxicities during treatment and within 30 days of completing SBRT in phase 1, and the percent of patients with a best RECIST response of complete response or partial response through month 6 in phase 2.

Then in the multicenter, randomized, double-blind, placebo-controlled GRECO-2 study, investigators aim to evaluate rucosopasem in patients aged 18 years and older with histologically or biopsy-proven adenocarcinoma of the pancreas.³ In the absence of histologic confirmation, cytology is acceptable. Patients with newly diagnosed non metastatic pancreatic cancer may be eligible to receive SBRT as well, as judged by a tumor board.

Additional requirements include having completed at least 6 weeks of chemotherapy consisting of FOLFIRINOX, modified FOLFIRINOX, or a gemcitabine-based doublet regimen prior to initiating SBRT, confirmation of nonmetastatic disease via CT scan at screening, an ECOG performance status between 0-2, and adequate end-organ function.

The trial plans to randomly assign patients to receive either rucosopasem or placebo given as a 15-minute IV infusion plus SBRT. The primary end point of the trial is to assess median OS and the secondary end point is progression-free survival from the point of SBRT completion.

REFERENCES:

1. Galera announces FDA orphan drug designation granted to rucosopasem for pancreatic cancer. News release. Galera Therapeutics. May 18, 2023. Accessed May 19, 2023. https://bit.ly/3MFG0Bc

2. Phase I/II study of SBRT and GC4711 for centrally located or large NSCLC (GRECO-1). ClinicalTrials.gov. Updated February 8, 2023. Accessed May 19, 2023. https://clinicaltrials.gov/ct2/show/NCT04476797

3. Phase 2b study of GC4711 in combination with SBRT for nonmetastatic pancreatic cancer. ClinicalTrials.gov. Updated May 18, 2023. Accessed May 19, 2023. https://clinicaltrials.gov/ct2/show/NCT04698915