The primary end point of the ROMAN trial was not reached after avasopasem was found to not significantly reduce the incidence of severe oral mucositis. A full analysis of the results is ongoing.
Avasopasem manganese (avasopasem) does not significantly reduce the incidence of severe oral mucositis (SOM) in patients with locally advanced head and neck cancer, according to phase 3 study results announced in a press release by Galera Therapeutics, Inc.
Avasopasem is a selective small molecule dismutase mimetic. It was previously granted a fast track therapy designation by the FDA for the reduction of radiotherapy induced SOM with or without systemic therapy.
“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 endpoint,” said Mel Sorensen, MD, president and chief executive officer of Galera, 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.”
These results fail to meet the primary end point of the phase 3 ROMAN study (NCT03689712) which compared avasopasem to placebo. The randomized, parallel assignment, quadruple masking, study has an actual enrollment of 455 participants and an estimated completion date of December 2023. The primary end point of the study is the cumulative incidence of SOM.
During the study, patients were randomized 3:2 to receive either avasopasem or placebo on days they were scheduled to receive radiotherapy.
An analysis study found a 16% relative reduction in the incidence of SOM in the avasopasem treatment group. The rate of SOM in the experimental arm was 54% versus 64% in the placebo group (P =0.113). Additionally, a 56% relative reduction in the length of SOM duration was observed. The median SOM days in the experimental arm was 8 days versus 18 days in the placebo arm (P =0.011). The incidence of grade 4 SOM in the experimental group was 24% versus 33% in the control group, amounting to a 27% relative reduction in severity.
In terms of safety, avasopasem was well tolerated.
“We continue to be excited about the potential of our second dismutase mimetic product candidate, GC4711, in clinical-stage development to augment the anti-cancer efficacy of stereotactic body radiation therapy [SBRT] in patients with non-small cell lung cancer [NSCLC] and locally advanced pancreatic cancer [LAPC]. We recently initiated a Phase 2b trial of GC4711 in combination with SBRT in LAPC based on promising tumor and survival outcome benefits observed in a Phase 1/2 pilot trial. In addition, enrollment is ongoing in a Phase 1/2 trial of GC4711 in combination with SBRT in patients with NSCLC. We look forward to providing updates as these trials progress,” said Sorensen in a press release.
In order to participate in the study, patients must have had squamous cell carcinoma of the head and neck, planned on receiving radiotherapy and standard cisplatin monotherapy, be 18 years of age or older, and ECOG score of ≤ 2, adequate hematologic, renal, and liver function, and not be pregnant. Patients with prior radiotherapy in the region of the study, metastatic disease, prior induction chemotherapy, receiving any other investigational agent, inability to eat solid food at baseline, active infectious disease, or a known HIV infection were not eligible to participate.