Pembrolizumab in MMR-Proficient Metastatic Colorectal Cancer Pharmacologically Primed to Trigger … (NCT03519412) | Clinical Trial Compass
CompletedPhase 2
Pembrolizumab in MMR-Proficient Metastatic Colorectal Cancer Pharmacologically Primed to Trigger Hypermutation Status
Italy107 participantsStarted 2019-01-23
Plain-language summary
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.
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. Histologically confirmed diagnosis of metastatic colorectal cancer.
✓. Documented RAS extended mutations in the archival sample (cohort P only).
✓. ECOG performance status 0-1.
✓. SCREENING phase informed consent signed.
✓. Understanding and accepting the need for undergoing two tumor biopsies if eligible for PRIMING Phase.
✓. Age ≥ 18 years.
✓. Availability of all diagnostic FFPE blocks (primary tumor and or metastases), or at least 20 slides (primary tumor and/or metastases). Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.
✓. Normal organ functions.
Exclusion criteria
✕. A woman of child bearing potential who has a positive urine pregnancy test within 72 hours prior to allocation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
What they're measuring
1
Overall Response Rate (ORR)
Timeframe: 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.
Trial details
NCT IDNCT03519412
SponsorIFOM ETS - The AIRC Institute of Molecular Oncology
✕. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
✕. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks \[could consider shorter interval for kinase inhibitors or other short half-life drugs\] prior to allocation.
✕. Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
✕. Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
✕. Has received prior radiotherapy within 2 weeks of start of study treatment (with pembrolizumab). Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
✕. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
✕. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.