NEW YORK – Gritstone Oncology announced Thursday morning that Phase I data for its new neoantigen therapy showed the treatment to be well-tolerated in patients. In addition, the investigators found that the neoantigens seemed to provoke strong immune responses in four solid tumor patients. The results were presented at the European Society for Medical Oncology Immuno-Oncology Congress in Geneva, Switzerland.
Gritstone's precision medicine strategy uses its artificial intelligence-based EDGE platform to analyze tissue from a routine biopsy for relevant tumor-specific peptide sequences, or neoantigens, presented on a patient’s tumor cells. Then, the firm develops an immunotherapy based on the patient's tumor-specific neoantigens (TSNA) in order to induce a personalized immune response from CD8+ T-cells that could eradicate tumor cells.
Gritsone's lead candidate is a personalized immunotherapy, dubbed GRANITE-001. It's an intramuscularly-administered injection that delivers a cassette made up of the top 20 predicted patient-specific TSNA derived from the patient’s tumor.
In the Phase I GO-004 study, GRANITE-001 is being evaluated in combination with immune checkpoint inhibitors for treatment of patients with advanced solid tumors, including microsatellite-stable colorectal cancer (MSS CRC), gastroesophageal cancer, metastatic non-small cell lung cancer, and bladder cancer.
In July 2018, Emeryville, California-based Gritstone entered into a collaboration with Bristol-Myers Squibb to examine the safety and tolerability of GRANITE-001 in combination with PD-1 immune checkpoint inhibitor nivolumab (Bristol-Myers Squibb's Opdivo) and in combination with nivolumab plus anti-CTLA-4 antibody ipilimumab (Bristol-Myers Squibb's Yervoy) in patients with advanced solid tumors. Early efficacy from this collaboration will be presented in 2020.
The US Food and Drug Administration also granted GRANITE-001 fast track designation in late 2018 for the treatment of colorectal cancer.
The first dosing cohort had three advanced cancer patients, including two with gastroesophageal adenocarcinoma and one with NSCLC, who progressed from prior anti-PD-L1 therapy.
This is the first-in-human study with this therapeutic approach, Gritstone said. Grade 1/2 adverse events were observed in study participants, and their symptoms were consistent with an inflammatory immune reaction.
Dose-escalation will continue in the Phase I portion of the Phase I/II trial until researchers establish an ideal dose for further investigation in Phase II. Researchers will also monitor for efficacy of the treatment through measures like using in-study biopsies to examine neoantigen-specific T-cell infiltration of tumors.
In a call with investors on Thursday, Gritstone said it expected to share all early clinical efficacy data for Phase I in the next six months and launch Phase II in the second half of 2020.
Phase II will aim to demonstrate proof of concept through single-arm cohort expansions into non-T-cell inflamed tumors like MSS colorectal cancer and in randomized cohorts in patients with more inflamed tumors, like in lung, gastric or bladder cancer.
Gritstone is simultaneously investigating an "off-the-shelf" version of GRANITE-001, called SLATE-001, in the Phase I GO-005 trial. SLATE-001 uses the same delivery approach as GRANITE-001 but contains a fixed cassette with TSNAs that are shared across a subset of cancer patients, rather than having a cassette unique to an individual patient.