The dismutase mimetic avasopasem manganese was not found to significantly reduce the incidence of severe oral mucositis in patients with locally advanced head and neck cancer who were receiving standard-of-care radiotherapy, missing the primary end point of the phase 3 ROMAN trial.
The dismutase mimetic avasopasem manganese (GC4419) was not found to significantly reduce the incidence of severe oral mucositis (SOM) in patients with locally advanced head and neck cancer who were receiving standard-of-care (SOC) radiotherapy, missing the primary end point of the phase 3 ROMAN trial (NCT03689712).1
Avasopasem reduced the incidence of SOM by 54% vs 64% with placebo; this translated to a relative reduction of 16% in this population (P = .113).
Moreover, a 56% relative reduction in the number of days of SOM was reported in the investigative vs control arms. The number of days of SOM with avasopasem was 8 days vs 18 days with placebo (P = .011). A 27% relative reduction in severity of SOM was observed, with avasopasem reducing severity by 24% vs 33% with placebo (P = .167).
Galera Therapeutics, Inc., the drug developer, shared that they will continue to examine the results from the trial.
“While the data, as in previous trials, showed reductions in the incidence, duration, and severity of SOM, we are surprised and disappointed that the trial did not achieve statistical significance in its primary end point,” Mel Sorensen, MD, president and chief executive officer of Galera Therapeutics, Inc., stated in a press release. “We would like to extend our heartfelt thanks to the patients who participated in this trial while they underwent radiotherapy for head and neck cancer. As we evaluate next steps for this program, we remain committed to our goal of transforming radiotherapy in cancer treatment with our selective dismutase mimetics.”
The double-blind, placebo-controlled, phase 3 ROMAN trial enrolled a total of 455 patients with locally advanced head and neck cancer who were receiving 7 weeks of SOC radiotherapy plus cisplatin.
To be eligible for enrollment, patients needed to be 18 years of age or older, have an ECOG performance status of 0 to 2, and acceptable hematologic, renal, and liver function.2 Patients could not have tumor of the lips, larynx, hypopharynx, nasopharynx, sinuses, or salivary glands, nor could they have metastatic disease. If patients received prior radiotherapy to the region of the study cancer, previous induction chemotherapy, or any approved or investigational anticancer agent beyond those provided in the study, they were excluded.
Study participants were randomized 3:2 to receive 90 mg of avasopasem or placebo via a 60-minute infusion on the days they received their radiation therapy. The primary end point of the trial was cumulative incidence of SOM, and key secondary end points were number of days of SOM and severity of SOM.
Previously, the safety and efficacy of avasopasem was compared with placebo to reduce the duration, incidence, and severity of SOM in patients with head and neck cancer who were receiving concurrent radiotherapy as part of a multi-institutional, randomized, double-blind, phase 2b trial.3
The trial enrolled 223 patients who had stage III to IVB, nonmetastatic, oral cavity or oropharyngeal squamous cell cancer and an ECOG performance status of 0 to 2, who were slated to receive treatment with standard fractionation intensity-modulated radiation therapy (IMRT) and concurrent cisplatin at 80 mg/m2 to 100 mg/m2 every 3 weeks or 30 mg/m2 to 40 mg/m2 weekly, given definitively or following surgical resection.
IMRT was given in 2.0 to 2.2 fractions administered daily, Monday through Friday, to a cumulative tumor dose of 60 Gy to 72 Gy. Study participants were randomized 1:1:1 to receive 30 mg of avasopasem, 90 mg of the agent, or placebo.
Patients were stratified based on cisplatin schedule and human papillomavirus status.
The primary end point of the trial was SOM duration, and secondary end points included SOM incidence at any time during IMRT or through 60 Gy of IMRT, and severity at any time during IMRT.
Of the 223 patients enrolled to the trial, 217 received at least 1 infusion of avasopasem or placebo. The median age of study participants across the arms was 57 years (range, 30-84), 86% were male, 66% had an ECOG performance status of 0, and 77% of patients had an oropharyngeal tumor site. The delivery of IMRT plus cisplatin was balanced across the arms and it did not appear to compromise the addition of avasopasem.
Results showed that 90 mg of avasopasem resulted in a significant reduction of SOM duration vs those who were given placebo (P < .024). The median SOM duration in the 90-mg arm was 1.5 days vs 19 days with placebo; this reflected a 34% relative reduction of SOM incidence at any time during IMRT (nominal P = .009).
The incidence of grade 4 oral mucositis at any time during IMRT was 16% with 90 mg of avasopasem vs 30% with placebo (nominal P = .045) and SOM incidence through 60 Gy was 37% and 58%, respectively (nominal P = .010). Moreover, the cumulative incidence of SOM was progressively lower in the 90-mg arm vs the placebo arm at radiation therapy delivery landmarks of 30 Gy, 40 Gy, 50 Gy, and 60 Gy.
“We continue to be excited about the potential of our second dismutase mimetic product candidate, GC411, in clinical-stage development to augment the anticancer efficacy of stereotactic body radiation in patients with non–small cell lung cancer and locally advanced pancreatic cancer,” Sorensen added in the release.