MNK Inhibitor AUM001 in Combination With Either Pembrolizumab or Irinotecan to Treat Metastatic Colorectal Cancer

Required: MSH2 microsatellite stable

Only subjects with CRC MSS will be enrolled in module 2, arm B'

Allowed: MSH2 microsatellite instability-high

CRC MSI-H patients should have been treated with a checkpoint inhibitor and have progressed on such therapy or found to be resistant, refractory or intolerant to the checkpoint inhibitor

Allowed: BRAF V600E

patients with driver mutations for which an FDA approved therapy is available such as BRAF V600E, HER2 or NTRK should have been offered such therapy prior to study entry

Allowed: HER2 (ERBB2) driver mutation

patients with driver mutations for which an FDA approved therapy is available such as BRAF V600E, HER2 or NTRK should have been offered such therapy prior to study entry

Allowed: NTRK1 driver mutation

patients with driver mutations for which an FDA approved therapy is available such as BRAF V600E, HER2 or NTRK should have been offered such therapy prior to study entry

Allowed: NTRK2 driver mutation

patients with driver mutations for which an FDA approved therapy is available such as BRAF V600E, HER2 or NTRK should have been offered such therapy prior to study entry

Allowed: NTRK3 driver mutation

patients with driver mutations for which an FDA approved therapy is available such as BRAF V600E, HER2 or NTRK should have been offered such therapy prior to study entry

Must have received: cytotoxic chemotherapy

Subjects who have had >2 lines of prior therapy for their CRC

Must have received: irinotecan (irinotecan)

Prior use of irinotecan or irinotecan containing regimens is permitted

Must have received: checkpoint inhibitor

CRC MSI-H patients should have been treated with a checkpoint inhibitor and have progressed on such therapy or found to be resistant, refractory or intolerant to the checkpoint inhibitor

Must have received: targeted therapy (VEGF/R antibody, EGFR antibody, encorafenib, cetuximab)

patients with an available molecularly targeted therapy such as antibodies targeting VEGF/R, EGFR, encorafenib/cetuximab, prior to study entry

Must have received: 5-fluorouracil containing regimen (5-fluorouracil)

failed an established 5-fluorouracil containing regimen

Must have received: oxaliplatin based or irinotecan-based combination therapy (oxaliplatin, irinotecan)

progressed after oxaliplatin based or irinotecan-based combination therapy

Cannot have received: anti-PD-1 therapy

Exception: excluded only if discontinued due to Grade 3 or higher irAE

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, and was discontinued from that treatment due to a Grade 3 or higher irAE