andecaliximab (GS-5745)

Taken together, the results of the current study indicated that seven hub genes including COL1A2, COL5A1, COL5A2, SERPINH1, MMP9, SPARC, and COL1A1 which were upregulated in CRC could be used as a diagnostic and progression biomarker of CRC. On the other hand, miR-940 which targets SERPINH1 could be used as a potential biomarker of CRC. More ever, Andecaliximab, Carboxylated glucosamine, Marimastat, Tozuleristide, S-3304, Incyclinide, Curcumin, Prinomastat, Demethylwedelolactone, Bevacizumab, Ocriplasmin , and Collagenase clostridium histolyticum were introduced as therapeutic agents for CRC which their therapeutic potential should be evaluated experimentally.

ADX monotherapy was ineffective at blocking initial MMP-dependent events of HNSCC invasion, likely due to redundant functions of additional non-targeted MMPs produced by tumor cells and microenvironment. Combination of ADX with existing and emerging therapies targeting additional MMP activation pathways may warrant future investigation.

The andecaliximab-nivolumab combination demonstrated a manageable safety profile and promising clinical activity in patients with advanced gastric adenocarcinoma.NCT02862535.

Combination of ADX+NIVO had a favorable safety profile but did not improve efficacy compared with NIVO alone in patients with pretreated metastatic gastric or GEJ adenocarcinoma. HER2 positivity, higher TMB or GRB7, and lower TGF-β were associated with improved outcomes.

The addition of ADX to mFOLFOX6 did not improve OS in unselected patients with untreated human epidermal growth factor receptor 2-negative gastric or GEJ adenocarcinoma.

P1b, N=36, Terminated, Gilead Sciences | Completed --> Terminated; Study was terminated due to sponsor's decision to not pursue further development of andecaliximab in oncology

The combination of andecaliximab, a novel, first-in-class inhibitor of matrix metalloproteinase 9, with gemcitabine and nab-paclitaxel in patients with advanced pancreatic adenocarcinoma provided a median progression-free survival of 7.8 months and objective response rate of 44.4%. The majority of systemic biomarkers related to matrix metalloproteinase 9 activity and immune suppression increased at 2 months, whereas biomarkers related to tumor burden decreased. Although this study demonstrates promising results with andecaliximab plus chemotherapy in patients with advanced pancreatic adenocarcinoma, andecaliximab was not associated with a survival benefit in a phase III study in patients with advanced gastric/gastroesophageal junction carcinoma.

P1b, N=36, Completed, Gilead Sciences | Trial primary completion date: May 2019 --> Oct 2019

Background: A phase 1b study was conducted in Japanese patients with >2nd line advanced gastroesophageal adenocarcinoma (GEA) to evaluate the safety, tolerability and explore efficacy and biomarkers, of andecaliximab (ADX), an anti-MMP9 monoclonal antibody, in combination with nivolumab (nivo). The observation that baseline levels of LAG3+CD8+ T cells and DCs were higher in responders is consistent with a prior anti-tumor immune response. Transient decreased peripheral CD8+ T cells might reflect T-cell trafficking into tumor in response to immunotherapy, and increased peripheral CTLA-4+ CD4+ T cells may also relate to tumor-localized response. Although in a very small number of patients, the observations are consistent with early changes in peripheral immune cells that may relate to response to immunotherapy.

Background: A phase 1b study was conducted in Japanese patients with >2nd line advanced gastroesophageal adenocarcinoma (GEA) to evaluate the safety, tolerability and explore efficacy and biomarkers, of andecaliximab (ADX), an anti-MMP9 monoclonal antibody, in combination with nivolumab (nivo). The observation that baseline levels of LAG3+CD8+ T cells and DCs were higher in responders is consistent with a prior anti-tumor immune response. Transient decreased peripheral CD8+ T cells might reflect T-cell trafficking into tumor in response to immunotherapy, and increased peripheral CTLA-4+ CD4+ T cells may also relate to tumor-localized response. Although in a very small number of patients, the observations are consistent with early changes in peripheral immune cells that may relate to response to immunotherapy.