Gritstone Oncology and Bristol-Myers Squibb are partnering to test the former's personalized neoantigen treatment in combination with the latter's Opdivo and Yervoy in patients with advanced solid tumors. They expect to start a phase 1 trial before the end of the year.
The duo will first evaluate GRANITE-001 in tandem with Opdivo in patients with common solid tumors, such as metastatic non-small cell lung cancer and gastroesophageal, bladder and colorectal cancers, the companies said in a statement. The two-part phase 1 dose escalation trial will also test GRANITE-001 with systemic Opdivo and localized injection of Yervoy.
Gritstone's approach involves identifying which tumor-specific neoantigens (TSNAs) a patient has, using machine learning to figure out which candidate is most likely to activate tumor-specific T cells and then delivering personalized synthetic TSNAs. GRANITE-001, Gritstone's lead asset, is given in two parts—first a priming adenoviral vector, followed by monthly boosters of an RNA vector, each containing the same 20 patient-specific TSNAs.
“The emergence of immunotherapies in the last decade has transformed the way we think about treating cancer, yet there remains a need for new therapies, which can initiate immune system recognition of tumors,” said Gritstone CEO Andrew Allen, Ph.D. “We have developed our programs using insights from our proprietary tumor antigen discovery platform, EDGE, together with an immunotherapy platform which has demonstrated the ability to elicit an enhanced antigen-directed T-cell response in preclinical primate models. We are excited to work closely with the experienced Bristol-Myers Squibb team to advance this novel combination approach into clinical trials.”
Gritstone has deep coffers to advance its vision—the Bay Area biotech reeled in a $102 million series A in 2015 and topped that up with a $92.7 million second round last September. And it's got a deep bench to execute its plans—Allen cofounded Clovis Oncology back in 2009, CTO Roman Yelensky was formerly a VP at Foundation Medicine, CSO Karin Jooss, is an ex-Pfizer cancer immunotherapy chief, and CMO Raphaël Rousseau joined from Genentech, where he set up the pediatric oncology drug development unit.
Gritstone is just one player in the immuno-oncology space that's trying to figure out which patients respond to immunotherapies and why. Art Krieg's Checkmate Pharmaceuticals is working to boost the efficacy of PD-1 blockers, such as Opdivo, by making "cold" tumors "hot." Earlier this year, the company presented data showing its CMP-001, a toll-like receptor 9 (TLR9) agonist, delivered with Keytruda, reversed PD-1 resistance in advanced melanoma patients who had already failed a prior anti-PD-1 treatment.