BMS is pushing forward with its internal IDO1 program and showing off early-stage data from its Phase I/IIa combination trial of Opdivo plus BMS-986205, an IDO1 inhibitor.
Bristol-Myers Squibb is pushing forward with its internal IDO1 program and showing off early-stage data from its Phase I/IIa combination trial of Opdivo plus BMS-986205, an IDO1 (indoleamine 2,3-dioxygenase 1) inhibitor.
BMS said the combination of the two drugs was having a positive treatment effect in the early stages. Findings for anti-tumor activity were reported in two cohorts of the Phase I/IIa trial -- bladder cancer and cervical cancer. In the bladder cancer cohort, the objective response rate (ORR) and disease control rate (DCR) were 32 percent and 44 percent, respectively. In the cervical cancer cohort, the ORR was 14 percent and DCR was 64 percent.
The drug combination performed even better when PD-L1 was factored into the equation. In patients who express PD-L1 of 1 percent or more, ORR was 46 percent and 25 percent in the bladder and cervical cancer cohorts, respectively, BMS said. In patients with PD-L1 expression levels of less than 1 percent, ORR was 22 percent in the bladder cancer cohort and no response was observed in cervical cancer patients.
BMS released the data ahead of Saturday’s presentation at the Society for Immunotherapy of Cancer in Maryland.
Earlier this year, BMS presented an abstract at the American Association of Cancer Research annual meeting showing off BMS-986205. During that presentation, evidence of substantial serum kyn reduction was observed in various dosed by patients taking BMS-986205. Faoud Namouni, BMS’s head of oncology development, told reporters that the company’s IDO “has the potential to be one of the most potent in the class.”
Mark Rutstein, BMS’ IDO development lead, said the company is pursuing transformative research to better understand tumor evasion mechanisms to help inform potential new treatment options for patients with advanced cancers. BMS-986205 has shown encouraging characteristics, including potent and selective inhibition of IDO1, as well as pharmacokinetic data that support once-daily dosing, he added.
“The preliminary response observed with BMS-986205 plus nivolumab in this study adds to our understanding of this combination, and together with the increases in tumor CD8 positive T cells and decreases in kynurenine, suggests a potent effect, which warrants further investigation across advanced cancers,” the study’s lead investigator Jason Luke, an assistant professor of medicine at the University of Chicago, said in a statement.
Bristol-Myers Squibb is evaluating BMS-986205 in combination with Opdivo across several advanced cancers, and recently initiated a Phase III study evaluating this combination in patients with previously untreated metastatic or unresectable melanoma.
The BMS presentation is taking place while one of its developmental partners for IDO1 therapies is in court facing off against a company BMS acquired in 2015. Incyte Corporation has levelled charges of stealing company secrets against the founders of Flexus Biosciences over the hiring of Incyte’s former chief scientific officer who had access to Incyte’s scientific research. Incyte claimed Flexus Chief Executive Officer Terry Rosen and research director Juan Jaen hired away Incyte’s chief scientist Jordan Fridman so Flexus could get its hands on Incyte’s Indoleamine 2,3-Dioxygenase 1 (IDO1) secrets.
Incyte is not specifically targeting BMS in its lawsuit. Earlier this year, the two companies forged a deal to evaluate the combination of epacadostat, an investigational oral selective IDO1 enzyme inhibitor, and BMS’ Opdivo as a first-line therapy for non-small cell lung cancer across the spectrum of PD-L1 expression and first-line treatment for head and neck cancer.
