KEY TAKEAWAYS
- The MAYA trial is a phase II trial evaluating an immune-sensitizing strategy for patients with microsatellite-stable and MGMT-silenced (mCRC).
- The trial’s primary aim was to evaluate the efficacy and safety of temozolomide priming followed by a combination of low-dose ipilimumab and nivolumab in these patients.
- Grade 3-4 immune-related adverse events were skin rash (6%), colitis (3%), and hypophysitis (3%).
- The MAYA study provided proof of concept that this treatment strategy may induce durable clinical benefits in MSS and MGMT-silenced mCRC.
Patients with microsatellite-stable (MSS) and O6-methylguanine-DNA methyltransferase (MGMT)-silenced metastatic colorectal cancer (mCRC) will participate in a single-arm, multicenter phase II trial testing the efficacy and safety of an immune-sensitizing strategy involving temozolomide priming followed by the combination of low-dose ipilimumab and nivolumab. Centralized pretreatment screening for MSS and MGMT silencing in patients with previously treated mCRC (i.e., lack of MGMT expression by immunohistochemistry plus MGMT methylation by pyrosequencing). Patients who qualified for the study were given two priming cycles of oral temozolomide 150 mg/sqm once daily, days 1-5, every 4 weeks (first treatment part), and then, in the absence of progression, were given the same regimen in combination with ipilimumab 1 mg/kg every 8 weeks and nivolumab 480 mg every 4 weeks (second treatment part). Patients who began the second part of treatment were included in the progression-free survival (PFS) analysis, with a rate of at least 4 out of 27 subjects remaining progression-free after 8 months as the primary endpoint.
From the initial pool of 716 patients, 204 (29%) were found to be molecularly eligible, and 135 have begun the initial phase of treatment. Although 102 patients (76%) were removed from the study due to death or disease progression during temozolomide priming, 33 patients (24%) who achieved disease control initiated the second treatment part and constituted the final study population. The 8-month PFS rate was 36% after a median follow-up of 23.1 months (IQR: 14.9-24.6 months). The overall response rate was 45%, and the median progression-free survival and overall survival were 7. Skin rash (6%) was the most common immune-related adverse event, followed by colitis (3%) and hypophysitis (3%). There were no unanticipated side effects or treatment-related fatalities. The MAYA study demonstrated the feasibility of combining low-dose ipilimumab and nivolumab in treating MSS and MGMT-silenced mCRC after priming course temozolomide.
Source: https://pubmed.ncbi.nlm.nih.gov/35258987/
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT03832621
Morano F, Raimondi A, Pagani F, Lonardi S, Salvatore L, Cremolini C, Murgioni S, Randon G, Palermo F, Antonuzzo L, Pella N, Racca P, Prisciandaro M, Niger M, Corti F, Bergamo F, Zaniboni A, Ratti M, Palazzo M, Cagnazzo C, Calegari MA, Marmorino F, Capone I, Conca E, Busico A, Brich S, Tamborini E, Perrone F, Di Maio M, Milione M, Di Bartolomeo M, de Braud F, Pietrantonio F. Temozolomide Followed by Combination With Low-Dose Ipilimumab and Nivolumab in Patients With Microsatellite-Stable, O6-Methylguanine-DNA Methyltransferase-Silenced Metastatic Colorectal Cancer: The MAYA Trial. J Clin Oncol. 2022 May 10;40(14):1562-1573. doi: 10.1200/JCO.21.02583. Epub 2022 Mar 8. PMID: 35258987; PMCID: PMC9084437.
