The anti-PD-1 antibody CBT-501 (genolimzumab) may offer hope to colon cancer patients, according to preclinical data recently presented by CBT Pharmaceuticals, a life sciences oncology company based in Santa Clara, California.
During the ASCO-SITC Clinical Immuno-Oncology Symposium — held Feb. 23-25 in Orlando, Florida — CBT said that its CBT-501 therapy effectively stimulates various cells of the immune system, generating anti-tumor immunity, suppressing tumor growth and delaying tumor progression in a preclinical model of colon cancer.
“The strong in-vivo preclinical data suggest that CBT-501 may have clinical benefit in a variety of tumor types,” Sanjeev Redkar, PhD, the company’s president and CEO, said in a press release. “CBT-501’s novel epitope, with overlapping yet distinct regions compared to incumbent PD-1 inhibitors, may offer a point of differentiation in the clinical setting.”
During the presentation, CBT investigators showed how CBT-501 inhibits the binding of PD-L1 and PD-L2 to PD-1 through competitive action. It also highlighted CBT-501’s ability to enhance the activation of human T-cells, by increasing the release of IL-2 and INF-gamma.
The experiments, conducted in a mouse model expressing human PD-1 and implanted with a colon adenocarcinoma (MC38) cell line, further revealed that CBT-501 was able to inhibit tumor growth in a dose-dependent manner comparable or better than the PD-1 inhibitor Opdivo (nivolumab).
Opdivo is another human anti-PD-1 monoclonal antibody that works as an immune checkpoint inhibitor, blocking a signal that prevents activated T-cells from attacking the cancer, and thus allowing the immune system to clear the cancer.
“These studies support our commitment to advancing the clinical development of genolimzumab as an immuno-oncology therapy for many types of cancer,” said Gavin Choy, PharmD, chief operating officer at CBT. “Based on these findings, a Phase 1 dose escalation and dose and disease expansion study will be initiated in the first half of 2017.”
The Phase 1 multicenter, dose escalation study (NCT03053466) aims to determine the safety, tolerability and recommended dose of CBT-501 in people with advanced, relapsed or recurrent solid tumors. Select advanced solid tumor malignancies will receive escalating doses of CBT-501. The dose escalation will occur in three cohorts of patients with solid tumors until patients experience any dose limited toxicity, and until a maximum tolerated dose is determined.