cixutumumab (IMC A12)

P2, N=94, Active, not recruiting, National Cancer Institute (NCI)

P2, N=134, Completed, National Cancer Institute (NCI) | Phase classification: P1/2 --> P2

The addition of cituxumumab to lapatinib and capecitabine did not improve PFS or OS compared with lapatinib and capecitabine in patients with HER2-positive MBC.

Immunotherapies that have been evaluated in clinical trials for ACC include the immune checkpoint inhibitors pembrolizumab, nivolumab, and avelumab. Other immunotherapies that have been evaluated include the monoclonal antibodies figitumumab and cixutumumab directed against the ACC-expressed insulin-like growth factor 1 (IGF-1) receptor, the recombinant cytotoxin interleukin-13-pseudomonas exotoxin A, and autologous tumor lysate dendritic cell vaccine. These agents have shown modest clinical activity, although nonzero in the case of the immune checkpoint inhibitors. Clinical trials are ongoing to evaluate whether this clinical activity may be augmented through combinations with other immune-acting agents or targeted therapies.

Additionally, low specific activity radioimmunoconjugate led to complete tumor remission in 2/6 mice. The data suggest that efficacy of cixutumumab can be enhanced by radiolabeling with 225Ac at a low specific activity.

To examine RON-IGF1R crosstalk, we employed the clinical-grade monoclonal antibody IMC-RON8, alone and together with the IGF1R-antibody IMC-A12...Thus, this first report supports a role for RON in the metastatic progression of Ewing sarcoma. While principal molecular functions appear transferrable between carcinomas, Ewing sarcoma and possibly more common sarcoma subtypes, RON highlights that specific regulations of cellular networks and isoforms require better understanding to successfully transfer targeting strategies.

P2, N=64, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed

In new metastatic hormone-sensitive prostate cancer, addition of cixutumumab to androgen deprivation did not improve survival. Baseline risk and disease volume carried prognostic value for this distinct trial population, although disease volume added more prognostic information. PSA treatment response was a strong intermediate endpoint for survival.

Despite a strong scientific rationale for the combination, temsirolimus plus cixutumumab demonstrated limited antitumor activity and a greater than expected incidence of toxicity, including low-grade pneumonitis and hyperglycemia. Hence, the trial was stopped in favor of alternative androgen receptor/phosphatidylinositol 3-kinase-directed combinatorial therapies.

In new mHSPC, adding cixutumumab to AD did not improve survival measures. Baseline risk and disease volume carried prognostic value for this distinct trial population, though disease volume was a better predictor of survival. PSA treatment response was a strong intermediate endpoint for survival.

In new mHSPC, adding cixutumumab to AD did not improve survival measures. Baseline risk and disease volume carried prognostic value for this distinct trial population, though disease volume was a better predictor of survival. PSA treatment response was a strong intermediate endpoint for survival.