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Investigational agent DKN-01 promising for advanced MSS CRC

Presented by
Dr Meredith Pelster, Sarah Cannon Research Institute, TN, USA
Conference
ASCO GI 2024
Trial
Phase 2, DeFianCe
Doi
https://doi.org/10.55788/d6d8fe36
Encouraging anti-tumour activity was reported for a combination of chemotherapy, bevacizumab, and the investigational agent DKN-01 in the second-line treatment for patients with advanced microsatellite-stable (MSS) colorectal cancer (CRC). In the current study, the largest benefit was observed for patients with rectal/rectosigmoid junction cancer.

DKN-01 is an investigational IgG4 monoclonal antibody targeting DKK1, which is a regulator of the Wnt signalling pathway; a pathway that drives CRC [1]. The current part A of the phase 2 DeFianCe study (NCT05480306) tested a regimen of standard-of-care chemotherapy (FOLFIRI/FOLFOX) plus bevacizumab and DKN-01 as second-line treatment for 33 patients with advanced MSS CRC [2].

The best overall response rate (ORR) was 30%, partial responses only, and the disease control rate (DCR) was 93%. In patients with left-sided tumours (n=25) the ORR was 33% and the DCR was 100%. Furthermore, in patients with rectal or rectosigmoid tumours (n=15) the ORR was 46% and the DCR was 100%. The corresponding median progression-free survival in the overall population, left-sided tumour subgroup, and the rectal or rectosigmoid tumour subgroup was 6.3 months, 8.6 months, and 9.4 months, respectively.

Serious adverse events were documented in 21.2% of the participants, but only 1 of these events was deemed related to the investigational agent. Diarrhoea, fatigue, and neutropenia were the most common side-effects.

Dr Meredith Pelster (Sarah Cannon Research Institute, TN, USA) and co-researchers concluded that the second-line treatment regimen of standard-of-care chemotherapy plus bevacizumab and DKN-01 was well tolerated and displayed encouraging anti-tumour activity in a heterogeneous population of patients with advanced MSS CRC. Part B of the DeFianCe trial is currently enrolling.

  1. Giannakis M, et al. Nat Genet. 2014;46(12):1264-1266
  2. Pelster M, et al. DKN-01 plus bevacizumab and chemotherapy as second-line (2L) investigational therapy in advanced micro satellite (MSS) colorectal adenocarcinomas (CRC): DeFianCe trial. Poster 104, ASCO Gastrointestinal Cancers Symposium 2024, 18–20 January 2024, San Francisco, CA, USA.

 

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