IFOM ETS - The AIRC Institute of Molecular Oncology
Who can join
18 and older, any sex, with Colorectal Neoplasms or Microsatellite Instability. Patients with the condition only — healthy volunteers not accepted.
Results — posted to ClinicalTrials.gov
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Overall Response Rate (ORR)Primary· Tumor assessments every 8-9 weeks from date of enrollment (in Trial Phase of the study) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
Overall response rate (ORR) to pembrolizumab according to RECIST v1.1. An objective response is defined as either a CR or PR assessed by RECIST v1.1 at the discretion of the local investigator.
Group
Value
95% CI
TMZ-primed MMR-proficient (MMRp)
0
0 – 0
Overall Response Rate (ORR)Secondary· Tumor assessments every 8-9 weeks from date of enrollment (in Trial Phase of the study) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
Overall response rate (ORR) to pembrolizumab according to RECIST v1.1. An objective response is defined as either a CR or PR assessed by RECIST v1.1 criteria at the discretion of the local investigator.
Group
Value
95% CI
MMR-deficient (MMRd)
54.3
32.7 – 84.8
Progression Free Survival (PFS)Secondary· From the date of treatment initiation with pembrolizumab to the date of first documented progression or date of death from any cause, whichever came first, up to maximum 72 months.
Progression Free Survival (PFS) in pembrolizumab treated patients. PFS was estimated using the Kaplan-Meier method. Patient without disease progression were censored at the last follow-up visit available.
Group
Value
95% CI
TMZ-primed MMR-proficient (MMRp)
3.3
2.2 – 6.4
MMR-deficient (MMRd)
49.7
3.5 – NA
Overall Survival (OS)Secondary· Every 8-12 weeks from date of treatment initiation with pembrolizumab to the date of death due to any cause (up to maximum 72 months). A participant who has not died will be censored at last known date alive.
Overall Survival (OS) in pembrolizumab treated patients. OS was estimated using the Kaplan-Meier method. Patient without disease progression were censored at the last survival follow-up available.
Group
Value
95% CI
TMZ-primed MMR-proficient (MMRp)
5.6
2.9 – NA
MMR-deficient (MMRd)
NA
15.4 – NA
Safety and TolerabilitySecondary· From the time the first dose of study medication (either pembrolizumab or temozolomide) is administered until 30 days following discontinuation of study treatment.
Safety and Tolerability according to CTCAE version 4.03
All treatment-related Adverse Event (AE), any grade
Time frame: All-Cause Mortality monitored/assessed up to 72 months. Adverse Events monitored/assessed from the time the first dose of study medication (either pembrolizumab or temozolomide) is administered until 30 days following discontinuation of study treatment..
Reporting threshold: 5%.
Adverse-event reports describe events observed during the trial — not all are caused by the drug.
In this study, MMRd metastatic colorectal cancer (mCRC) patients who failed standard therapies will undergo treatment with pembrolizumab, while RAS-extended mutated MMR-proficient mCRC patients will be tested for o6-methylguanine-DNA-methyltransferase (MGMT) expression (IHC) and then for MGMT promoter methylation. MGMT IHC-negative, promoter methylation positive patients will be treated with temozolomide (TMZ). Patients progressing under temozolomide will be tested for tumor mutational burden (TMB) and proceed to pembrolizumab if TMB is \> 20 mutations/Mb. The primary study hypothesis is that tumors with acquired resistance to temozolomide become hypermutated and are sensitive to pembrolizumab.
Publications & conference data
8 peer-reviewed publications reference this trial (live from Europe PMC):
NCT06983639 — Randomized Trial Comparing Fecal Testing (FIT) to Colonoscopy for Post-polypectomy Surveillance
· NA
· recruiting
NCT07222800 — Symbiotic-GI-03: A Study to Learn About the Study Medicine Called PF-08634404 in Combination With Chemotherapy in Adult
· Phase 3
· recruiting
NCT07239479 — DEXDES Trial: Dexmedetomidine-Desflurane Combination in Laparoscopic Colectomy
· NA
· recruiting
NCT07262840 — Health Behavior Change in High-Risk Colorectal Cancer Individuals
· NA
· recruiting
NCT07257653 — The Safety and Efficacy of Cetuximab Beta Plus Fruquintinib With or Without Immune Checkpoint Inhibitorrs in First-line
· Phase 2
· recruiting
Other IFOM ETS - The AIRC Institute of Molecular Oncology trials
Trials by the same sponsor.
NCT06490536 — The Sagittarius Trial
· Phase 3
· recruiting
NCT04259944 — Post-surgical Liquid Biopsy-guided Treatment of Stage III and High-risk Stage II Colon Cancer Patients: the PEGASUS Tria
· Phase 2
· unknown
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by IFOM ETS - The AIRC Institute of Molecular Oncology
Last refreshed: 3 March 2026
Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03519412.