898P - Meta-analysis of two placebo-controlled trials of avasopasem manganese (AVA) in patients with locally advanced, head & neck cancer (LAHNC)

Background

Oral mucositis (OM) is severe in up to 70% of patients receiving standard chemoradiation (7 weeks of RT and concurrent cisplatin). Cisplatin contributes to the acute toxicity (acute kidney injury, tinnitus, myelosuppression) during treatment but also causes irreversible chronic kidney disease (CKD) in up to 30% of patients in the years following treatment. Two randomized, placebo-controlled, blinded studies, ROMAN (NCT03689712) and GT-201 (NCT02508389), evaluated avasopasem 90mg (AVA) for the reduction of severe OM (SOM, WHO grade 3-4) and both met their primary endpoints.

Methods

The ROMAN phase 3 (ITT N=407) and GT-201 phase 2b trials (ITT placebo and 90 mg N=144) results were aggregated using conventional methods for fixed-effects meta-analysis. In ROMAN, prospectively defined follow-up of serum creatinine (sCr) and estimated glomerular filtration rates (eGFR) were assessed every 3 months for 1 year following 7 weeks of CRT.

Results

The meta-analysis of ROMAN and GT-201 (N=551 [313 AVA/238 PBO]) showed a 19% relative reduction in SOM incidence (52% vs 64%; P=0.0053), 58% relative reduction in SOM duration (median, 8 vs 19 days; P=0.0002), 32% reduction in Grade 4 incidence (22% vs 32%; P=0.0102), and 28% delay in median days to SOM onset (median 50 vs 39 days; P=0.0005). Adverse event frequencies were mostly comparable between treatment groups with a trend towards reduction of certain IMRT- and cisplatin-related toxicities including tinnitus which was reported less with AVA in both studies. At 1-year follow-up, AVA was associated with significant improvements in preservation of eGFR (P=0.0008) and sCr (P=0.006) levels vs PBO. Grade 3+ CKD results through 12 months show 10% AVA vs 20% PBO (relative risk 0.55, P=0.0043).

Conclusions

AVA produced statistically significant, clinically meaningful improvement of SOM vs PBO that was consistent across multiple measures of SOM, with an adverse event profile consistent with expectations for IMRT/cisplatin. At 1-year follow-up, AVA appears to reduce cisplatin-related CKD in the study population.

Clinical trial identification

GTI-4419-301, 13 July 2020 (NCT03689712).

Editorial acknowledgement

Editorial (Sarah Hummasti, PhD) was provided by AOIC, LLC and funded by Galera Therapeutics, Inc.

Legal entity responsible for the study

Galera Therapeutics, Inc.

Funding

Galera Therapeutics, Inc.

Disclosure

N. Dunlap: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca. C. Anderson: Non-Financial Interests, Personal and Institutional, Speaker, Consultant, Advisor: Galera Therapeutics, Inc. C. Lee: Financial Interests, Personal and Institutional, Research Funding: Bayer, Merck, Decipher Genetics; Financial Interests, Personal and Institutional, Advisory Role: Bayer, Merck, Decipher Genetics; Financial Interests, Personal, Stocks or ownership: Axcend LLC, Kobold Medical LLC. J. Kelley: Financial Interests, Personal and Institutional, Research Funding: Galera Therapeutics, Inc. G. Walker: Financial Interests, Personal, Advisory Role: Galera Therapeutics, Inc.; Financial Interests, Personal and Institutional, Research Funding: Galera Therapeutics, Inc. V. Bar-Ad: Financial Interests, Personal and Institutional, Research Funding: Galera Therapeutics, Inc. D. Miller: Financial Interests, Personal and Institutional, Research Funding: Galera Therapeutics, Inc. V. King: Financial Interests, Personal, Ownership Interest: San Juan Cancer Center; Financial Interests, Personal, Leadership Role: San Juan Cancer Center. A. Peddada: Financial Interests, Personal, Stocks/Shares: Galera Therapeutics, Inc. D. Ciuba: Financial Interests, Personal and Institutional, Research Funding: Galera Therapeutics, Inc. F. Vincent: Financial Interests, Personal and Institutional, Research Funding: Galera Therapeutics, Inc. B. Muzyka: Financial Interests, Institutional, Research Funding: Galera Therapeutics, Inc. A. Gillespie-Twardy: Financial Interests, Personal and Institutional, Research Funding: Galera Therapeutics, Inc. S. Sonis: Financial Interests, Personal, Full or part-time Employment: Primary Endpoint Solutions ; Financial Interests, Personal, Leadership Role: Primary Endpoint Solutions ; Financial Interests, Institutional, Other, Contract work for study: Galera Therapeutics, Inc. E. Kennedy: Financial Interests, Personal, Full or part-time Employment: Galera Therapeutics, Inc.; Financial Interests, Personal, Stocks or ownership: Galera Therapeutics, Inc. D. Saunders: Financial Interests, Personal and Institutional, Research Funding: Galera Therapeutics, Inc.