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The safety, tolerability, pharmacokinetics, and preliminary antitumor activity of the novel agent XB002 is set to be examined in an upcoming phase 1 clinical trial that is expected to begin the second quarter of 2021.
The safety, tolerability, pharmacokinetics, and preliminary antitumor activity of the novel agent XB002 (formerly ICON-2) is set to be examined in an upcoming phase 1 clinical trial that is expected to begin the second quarter of 2021, according to a press release from Exelixis Inc.1
On April 5, 2021, the FDA announced that it had accepted an investigational new drug application for the agent to evaluate its safety and preliminary efficacy in patients with difficult-to-treat solid tumors. Investigators hypothesize that the next-generation, tissue factor–targeting antibody-drug conjugate (ADC) could potentially improve therapeutic index while providing an acceptable safety profile vs earlier ADCs that target tissue factor.
Preclinical data have indicated that XB002 has possible utility across several solid tumor cancer models and may improve tolerability compared with other tissue factor–targeting ADCs. Moreover, the agent has demonstrated significant tumor growth inhibition and complete regression in some cases.
“The acceptance of our investigational new drug application for XB002 gets us one step closer to our first biologic entering the clinic and learning more about its potential to help patients with difficult-to-treat cancers,” Gisela Schwab, MD, president of Product Development and Medical Affairs, as well as the chief medical officer at Exelixis, stated in a press release. “Considering XB002’s promising preclinical data and potential differentiation from other tissue factor-targeting ADCs, we look forward to initiating our phase 1 trial in patients with advanced solid tumors.”
XB002 is comprised of a human monoclonal antibody against tissue factor and is conjugated to a cytotoxic agent. The agent is internalized after binding to tissue factor on tumor cells, after which the cytotoxic agent is released; this can result in targeted tumor cell death, according to Exelixis Inc, the drug developer. Moreover, the agent utilizes proprietary linker-payload technology. Contrary to the efficacy observed with earlier ADCs, XB002 is able to bind to tissue factor without affecting coagulation cascade, according to preclinical findings.
Additional data from preclinical studies showed that XB002 binds to tissue factor on both human and non-human primate (NHP) cells with high affinity but does not impact coagulation as measured by FXa conversion and thrombin generation assays.2 Moreover, in NHPs, the agent was not found to cause neutropenia.
In a mouse xenograft of human pancreatic tumor cells, XB002 was found to be stronger than an ADC containing monomethyl auristatin E (MMAE) conjugated to the same anti–tissue factor antibody. In patient-derived xenograft models derived from several tumor types, the ADC was found to be highly active. Lastly, the agent had superior tolerability and exposure when directly examined in comparison with an MMAE ADC that utilized the same anti–tissue factor antibody in a study done in NHPs.
“The data…continue to support that potential and differentiate [XB002] from other anti–tissue factor ADCs,” Peter Lamb, PhD, executive vice president of Scientific Strategy and chief scientific officer of Exelixis, added in another press release on earlier data with the agent. “These promising results also underscore Exelixis’ ability to identify promising licensing opportunities as part of our ongoing pipeline expansion strategy, which includes both internally developed and in-licensed programs.”