On December 12, 2019 Gritstone Oncology, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company developing the next generation of cancer immunotherapies to fight multiple cancer types, reported that the company has presented preliminary Phase 1 GRANITE immunogenicity data demonstrating the rapid, robust and consistent induction of large numbers of CD8+ T cells against multiple neoantigens in four solid tumor patients with available IFN-g ELISpot data (up to 3,000 IFN-g spot forming units per 106 PBMCs were generated, as measured by overnight ELISpot) within the first two dosing cohorts (Press release, Gritstone Oncology, DEC 12, 2019, View Source [SID1234552355]). Importantly, these T cells were also able to produce IL-2 and Granzyme B, demonstrating that they have cytotoxic potential. In addition to priming naive CD8+ T cells against encoded neoantigens, the data demonstrate that GRANITE can also stimulate the expansion of pre-existing T-cell populations. Safety data from five patients receiving GRANITE and three patients receiving SLATE across the first two dose levels indicate that the immunotherapies were well-tolerated with no dose-limiting toxicities observed. Dose escalation continues. These results were presented today in an oral session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology Congress in Geneva, Switzerland.
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"We are thrilled to observe very robust, polyfunctional CD8+ T cells against predicted neoantigens even at the first dose level of our phase 1 study," said Andrew Allen, M.D., Ph.D., co-founder, president and chief executive officer of Gritstone Oncology. "We view these preliminary results as important de-risking data, demonstrating the unprecedented immunogenicity of our heterologous prime/boost vaccine platform at its lowest dose, in combination with nivolumab. Pre-clinical data have shown a clear dose response where higher doses of the self-amplifying RNA boost vaccination, as well as the addition of anti-CTLA-4, further increase the number and function of CD8+ T cells. Notably, the starting dose of self-amplifying RNA was conservative since this is the first in-human study with this therapeutic approach. Therefore, we look forward to presenting mature data at higher doses with additional patients receiving the full immunotherapy regimen in several months."
In the GRANITE Phase 1 GO-004 study, the first dosing cohort consisted of three advanced cancer patients, including two gastroesophageal adenocarcinoma patients and one non-small cell lung cancer patient who had previously progressed on prior anti-PD-L1 therapy. From the second GRANITE dosing cohort, early ELISpot data was available from one microsatellite-stable
colorectal cancer patient. Most common adverse events in the GO-004 study were grade 1/2 fever and skin rash, consistent with an inflammatory immune reaction. In the SLATE Phase 1 GO-005 study, patients are still early in their course of treatment, and treatment-related adverse events have been limited to one injection site reaction and one case of grade 1/2 pruritus.
About GRANITE and SLATE Ongoing Phase 1/2 Clinical Studies
Gritstone’s GRANITE personalized immunotherapy delivers a cassette of 20 TSNA identified by the company using its proprietary Gritstone EDGETM artificial intelligence platform and tumor HLA peptide sequencing, representing tumor-specific neoantigens that are derived from the patient’s own tumor. GRANITE is being evaluated in combination with immune checkpoint blockade in a Phase 1/2 clinical study, referred to as GO-004, for the 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 the Phase 1 study, all patients receive a fixed dose of intramuscular adenovirus-based prime with three escalating doses (30, 100 and 300 µg) of intramuscular RNA-based boost vaccinations in combination with intravenous anti-PD-1 therapy. Following dose escalation of the RNA-based boost vaccine to 100 µg, subcutaneous anti-CTLA-4 is added to the treatment regimen in the third dosing cohort. GRANITE was granted Fast Track designation by the U.S. Food and Drug Administration for the treatment of MSS CRC.
Gritstone’s SLATE "off-the-shelf" immunotherapy delivers a cassette of 20 TSNA identified by the company using its proprietary EDGE artificial intelligence platform and tumor HLA peptide sequencing, representing mutated gene sequences that are shared across patients (such as K-RAS mutations). SLATE is being evaluated in combination with immune checkpoint blockade in a Phase 1/2 clinical study called GO-005 for the treatment of patients with advanced solid tumors, including metastatic non-small cell lung cancer, pancreatic ductal adenocarcinoma and microsatellite-stable colorectal cancer, as well as in patients with other solid tumor types who have relevant mutation/HLA (human leukocyte antigen) combinations. In the Phase 1 study, all patients receive a fixed dose of intramuscular adenovirus-based prime with three escalating doses (30, 100 and 300 µg) of intramuscular RNA-based boost vaccinations in combination with intravenous anti-PD-1 therapy. Following dose escalation of the RNA-based boost vaccine to 30 µg, subcutaneous anti-CTLA-4 is added to the treatment regimen in the second dosing cohort.
Investor Teleconference and Webcast
The company will host a conference call today, December 12, 2019 at 8:00 am ET to review its clinical programs, including the clinical data presented at ESMO (Free ESMO Whitepaper)-IO. The conference call can be accessed by dialing (866) 866-1333 or (404) 260-1421 and referencing conference ID number 49260042. A webcast of the call and accompanying slides will be available within the Investors & Media section of the Gritstone Oncology website at View Source An archived replay will be accessible for 30 days following the event.