MALVERN, Pa.—Galera Therapeutics, Inc. has reported interim data from the full patient population in its Phase 1/2 clinical trial of avasopasem manganese (GC4419), in combination with stereotactic body radiation therapy (SBRT), in patients with locally advanced pancreatic cancer (LAPC). The data were presented during the late-breaker special session of the American Society for Radiation Oncology (ASTRO) 2020 virtual Annual Meeting.
The randomized, double-blind, multicenter pilot dose escalation Phase 1/2 trial was designed to evaluate the safety and efficacy of GC4419 in combination with SBRT in patients with LAPC. After patients completed induction chemotherapy, they were randomized 1:1 to receive five-fraction SBRT, and 90 mg of either GC4419 or placebo by intravenous infusion one hour prior to each SBRT fraction.
In the interim analysis of the intent-to-treat population (n=42), median overall survival (OS) had not been reached at the data cutoff (August 24, 2020) in the GC4419 arm, compared to 38.7 weeks in the placebo arm. Six to eight weeks post-SBRT, patients underwent protocol-specified evaluation for resection, and seven underwent resection. Of the patients in the GC4419 arm who were surgically resected (n=5), all achieved clear/negative margins (R0); one achieved pathological complete response (pCR) and four achieved pathological partial response (pPR), compared to one R0 and pPR of the two surgically resected patients in the placebo arm.
“The survival rate in pancreatic cancer is dismal. Our goals for treatment are to extend survival and improve the potential for surgical resection, as surgery remains the only potentially curative therapy for pancreatic cancer,” noted Sarah Hoffe, M.D., section head of GI Radiation Oncology and Senior Member at Moffitt Cancer Center, trial first author and investigator. “These interim data signal the potential of dismutase mimetics, when combined with SBRT, to prolong survival in patients with LAPC. Further study of dismutase mimetics to expand the utility of SBRT in pancreatic cancer treatment is warranted.”
No statistically significant differences in progression-free survival (PFS) were observed between GC4419 and placebo. However, patients were censored for PFS at the date of surgical resection, or due to short interval follow up. Toxicity was comparable across both treatment arms, with no significant differences in acute (<90 days) or late (91-365 days) Grade 3+ toxicity post-SBRT.
The interim data includes all patients followed for a minimum of three months and 19 for more than one year. Galera plans to provide an additional update on this trial with at least one year of follow up on all patients in the second half of 2021.
“We’re encouraged by the favorable overall survival benefit in this difficult-to-treat cancer observed in the interim data in this trial, which is the first trial evaluating the anti-cancer activity of one of Galera’s dismutase mimetics in combination with SBRT. Galera’s dismutase mimetics are designed to improve radiation therapy by both increasing therapeutic antitumor efficacy at higher doses of radiation and by protecting normal cells, and we look forward to advancing the development of this potential combination therapy and expanding into other cancers to improve outcomes for patients undergoing radiotherapy for the treatment of cancer,” added Mel Sorensen, M.D., president and CEO of Galera Therapeutics.
Galera’s lead product candidate GC4419 is a highly selective small molecule superoxide dismutase (SOD) mimetic. It’s initially being developed for the reduction of radiation-induced severe oral mucositis (SOM). Avasopasem is designed to rapidly and selectively convert superoxide to hydrogen peroxide and oxygen, protecting normal tissue from the damage associated with radiation therapy.
Avasopasem is currently being studied in a Phase 2a trial for its potential to reduce the incidence of radiation-induced esophagitis in patients with lung cancer, and a Phase 2 trial in hospitalized patients who are critically ill with COVID-19. The U.S. Food and Drug Administration has granted Fast Track and Breakthrough Therapy designations to avasopasem manganese for the reduction of SOM induced by radiotherapy.
Galera plans to use observations from the GC4419 trial to further develop GC4711, its second superoxide dismutase mimetic clinical candidate, for use in combination with SBRT. The company also anticipates initiating a follow-on Phase 2 trial in pancreatic cancer with GC4711 in combination with SBRT in the first half of 2021.
Galera announced on October 22 that company has dosed its first patient in the Phase 1/2 GRECO-1 clinical trial of GC4711 in combination with SBRT in patients with non-small cell lung cancer (NSCLC). In preclinical studies, GC4711 increased the anti-cancer efficacy of radiotherapy and protected normal lung tissue.
The trial is supported in part by a recently awarded Small Business Innovation Research (SBIR) grant from the National Cancer Institute of the National Institutes of Health. The grant is for the investigation of Galera’s dismutase mimetics in combination with SBRT for the treatment of lung cancer.
“SBRT holds promise to deliver more efficient, targeted and potent radiotherapy to improve cancer outcomes. This trial builds on the pilot trial in combination with SBRT in patients with locally advanced pancreatic cancer and we are eager to embark on our exploration of the potential of Galera’s GC4711 to enhance the anti-cancer efficacy of SBRT,” stated Sorensen in a press release. “We’re grateful for the support provided by the SBIR grant, which further recognizes the potential of this combination.”
Following a safety run-in cohort, up to 66 NSCLC patients with locally advanced disease will receive GC4711 with SBRT, or placebo with SBRT, over five consecutive weekdays in the randomized, double-blind Phase 2 portion of the GRECO-1 trial. The trial is intended to assess the effects of GC4711 in combination with SBRT on tumor outcomes and lung injury.