Researchers Hope a New Drug Can Help Overcome Immunotherapy Resistance in Metastatic Cancers

A recently launched clinical trial of NTX1088 will determine if the novel drug can help overcome immune checkpoint inhibition resistance in patients with locally advanced or metastatic solid tumors.

The first patient has been dosed in a phase 1 clinical trial of NTX1088 — both alone and in combination with an anti-PD-1 immunotherapy agent — for patients with locally advanced or metastatic solid tumors, according to Nectin Therapeutics, the manufacturer of NTX1088.

NTX1088 works by blocking PVR, a protein on cancer cells that is associated to resistance to PD-1 and PD-L1 immune checkpoint inhibitors, like Opdivo (nivolumab), Yervoy (ipilimumab), Keytruda (pembrolizumab) and others. Blocking PVR also stops immune-suppressing signaling of TIGIT and CD96, which are both involved in helping tumor cells evade the immune system.

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“PVR blockade by NTX1088, with its first-in-class differentiated mechanism of action, has demonstrated compelling preclinical anti-tumor activity both as a monotherapy and in combination with other cancer immunotherapies,” said Dr. Pini Tsukerman, co-founder and chief scientific officer of Nectin, said in a company-issued press release. “Importantly, NTX1088 has potent activity in (immune checkpoint inhibition) refractive models where TIGIT or PD-1 blockade has failed to show a benefit.”

Phase 1 of the trial, which is being launched at The University of Texas MD Anderson Cancer Center in Houston, will include approximately 50 patients. Then, another 40 patients will be added to the second part of the trial.

The goal of the phase 1 portion of the trial is to determine the safety and tolerability of NTX1088, as well as an optimal dose for phase 2, known as the expansion stage, which will continue to analyze the safety and tolerability, as well as the efficacy and predictive biomarkers.

"NTX1088’s triple mechanism of action represents a unique approach to treating challenging cancers and we are excited by its potential to address a range of treatment-resistant tumors," said Ross Barrett, a founder and Managing Partner of Cancer Focus Fund, an organization providing funding and support to the trial.

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