A randomized, placebo-controlled phase 2 study of ganitumab or conatumumab in combination with FOLFIRI for second-line treatment of mutant KRAS metastatic colorectal cancer

Abstract

Conatumumab, but not ganitumab, plus FOLFIRI was associated with a trend toward improved PFS. Both combinations had acceptable toxicity.

From conventional chemotherapy to targeted therapy: use of monoclonal antibodies (moAbs) in gastrointestinal (GI) tumors

“…However, in metastatic pancreatic adenocarcinoma, the addition of ganitumab to gemcitabine showed trend towards improved 6 months survival rate compared to gemcitabine alone (57 vs. 50 %) [96]. As mentioned earlier, ganitumab + FOLFIRI in metastatic colorectal cancer failed to show any significant tumor response [94].…”

“…In a randomized phase II study, the efficacy and safety of conatumumab or ganitumab (a monoclonal antibody against the type 1 insulin-like growth factor receptor) combined with standard FOLFIRI chemotherapy as a second-line treatment in mCRC patients with mut KRAS tumors were analyzed. The primary end point was PFS; conatumumab plus FOLFIRI was associated with PFS advantage (6.5 vs 4.5 months respectively; P=0.998) while both combinations had acceptable toxicity [94]. A recent randomized phase Ib/II trial was conducted in patients with previously untreated mCRC to define the safety, tolerability, and efficacy of mFOLFOX6 plus bevacizumab (mFOLFOX6/bev) with conatumumab.…”

The insulin-like growth factor (IGF) axis as an anticancer target in prostate cancer

“…Besides members of the IGF regulatory network other biomarkers have also been discussed. For example, KRAS mutations were predictive for non-therapy response to the IGF1R monoclonal antibody ganitumab in colorectal cancer [87]. In contrast, in small cell lung cancer, KRAS mutations were found to be positive predictors for therapy response to IGF1R targeting agents [88].…”

Tumor necrosis factor-related apoptosis-inducing ligand-induced apoptotic pathways in cancer immunosurveillance: molecular mechanisms and prospects for therapy

“…110,111 Aside from HDACi and proteasome inhibitors, a broad range of standard chemotherapeutics have also demonstrated similar results to increase sensitivity in combination with TRAIL-receptor agonists. [85][86][87]112 Chemotherapeutics are efficient at killing tumor cells; however their ability (as single agents) to induce long-lasting immunity against tumors can be limited and drug-type dependent. [113][114][115][116] Therefore, a growing area of research is the combination of TRAIL-receptor agonists with cytokine therapy or immunomodulators to help elicit antitumor immunity.…”

“…Further preclinical and clinical trials combining the various mAbs with other treatments have shown some promising results, suggesting additive and/or synergistic roles for mAbs with current, standard therapies. [85][86][87] Most recently, a preclinical study from Tuthill et al demonstrated the synergistic relationship between the human anti-TRAIL-R2 mAb conatumumab and human rTRAIL dulanermin to kill primary ovarian cancer cells. 88 They revealed that conatumumab binds a different epitope within TRAIL-R2 than dulanermin, allowing the concomitant binding of both reagents resulting in enhanced cross-linking and apoptosis-inducing capacity.…”