Gritstone Announces Positive Clinical Data with GRANITE (Individualized Neoantigen Immunotherapy Program) during ESMO 2021 and Launch of Randomized Clinical Trial Program in Colorectal Cancer with Registrational Intent
- GRANITE individualized immunotherapy demonstrates objective evidence of efficacy in end-stage colorectal cancer (CRC) patients (3rd line or greater) who have “cold” tumors at baseline
- 44% molecular response rate (4/9) by ctDNA (circulating tumor DNA) analysis
- Molecular response associated with extended median overall survival >17 months
- 44% molecular response rate (4/9) by ctDNA (circulating tumor DNA) analysis
- Phase 2/3 randomized, controlled trial of maintenance GRANITE immunotherapy in newly diagnosed, metastatic, microsatellite-stable (MSS)-CRC patients expected to start in 1H 2022, has registrational intent and has been discussed with the FDA
- Randomized, controlled phase 2 trial of adjuvant GRANITE immunotherapy in MSS-CRC patients with stage II/III disease who are ctDNA+ after definitive surgery is expected to start in 1H22
Webcast today,
In the 26 patients treated in the study with metastatic solid tumors largely focused on MSS-CRC and gastro-esophageal adenocarcinoma (GEA), GRANITE immunotherapy demonstrated good tolerability, consistent and potent immunogenicity (CD8+ neoantigen-specific T cell induction in all subjects), and objective evidence of efficacy as measured by reduction in ctDNA (molecular response). In particular, MSS-CRC patients exhibited “cold” tumors at baseline, with low PD-L1 and IFN-g expression and low tumor mutational burden.
Based on these data, Gritstone has discussed the registrational path with the
“GRANITE is demonstrating a favorable safety and tolerability profile and is consistently inducing high numbers of neoantigen-specific CD8+ T cells” said
As of the
In MSS-CRC patients, where checkpoint inhibitors have shown minimal activity, GRANITE elicited a 44% molecular response rate in 9 evaluable patients (defined as a 50% or greater reduction in ctDNA from baseline) which is an increasingly well recognized objective efficacy biomarker for novel immunotherapy. Patients who demonstrated molecular response had median overall survival of >17 months (median not reached) whereas those without molecular response exhibited a median overall survival of 7.8 months, consistent with expected outcomes in 3rd line treatment of MSS-CRC.
MSS-CRC | All (n=121) | No Molecular Response (n=5) | Molecular Response (n=4) |
Median Overall Survival (months) | 8.7 | 7.8 | Not reached (>17) |
Median iPFS per iRECIST (months) | 3.9 | 2.0 | 11.8 |
Median PFS per RECIST (months) | 2.0 | 2.0 | 4.9 |
i=immune-based; PFS = progression-free survival; RECIST=Response Evaluation Criteria in Solid Tumors
1. 12 MSS-CRC patients treated; 9 patients eligible for analysis of ctDNA changes relative to baseline
A confirmed complete RECIST response was observed in a GEA patient (ctDNA negative at baseline). Multiple patients remained on treatment for over 6 months with lack of confirmed disease progression including 2/9 MSS-CRC patients receiving treatment beyond 12 months and one patient currently at 11+ months, which contrasts sharply with the expected outcome for these patients. 50% of patients (3/6) had a slow decrease in volume of multiple pulmonary metastasis during the first year of therapy, even though these objective radiological responses did not meet RECIST criteria. These radiological observations were associated with prolonged time on study and decrease in biomarkers such as ctDNA.
“The unmet need in our many patients with metastatic colorectal cancer is profound –third-line therapy offers limited additional benefit and checkpoint inhibitors are ineffective in this setting” said Dr.
Additional information about the trial can be found at www.clinicaltrials.gov, NCT03639714
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Webcast Information
To register for the webinar, please click here. The call and accompanying slides will be webcast live on the “Events” page under the “Investors & Media” section of the company’s website at www.gritstone.com. A replay of the webcast will be accessible at the same link approximately one day after its completion.
About GRANITE
Gritstone’s neoantigen-based immunotherapies are engineered to elicit a significant T-cell response (particularly CD8+ cytotoxic T cells) against mutation-derived tumor-specific neoantigens, or TSNA, that are identified by the company using its proprietary Gritstone EDGETM artificial intelligence platform and tumor HLA peptide sequencing. GRANITE is an individualized neoantigen-based immunotherapy and uses a priming adenoviral vector (GRT-C901) and self-amplifying mRNA vector (GRT-R902) to deliver personalized immunotherapy containing the relevant neoantigens. It is being evaluated in the Phase 2 portion of a Phase 1/2 clinical study in combination with checkpoint inhibitors for patients with microsatellite stable colorectal cancer (MSS CRC) who have progressed on FOLFOX/FOLFIRI therapy and a second cohort for patients with gastro-esophageal cancer who have progressed on chemotherapy (NCT03639714). GRANITE was granted Fast Track designation by the
About Gritstone
Gritstone Forward-Looking Statements
This press release contains forward-looking statements, including, but not limited to, statements related to the potential of Gritstone’s therapeutic programs; the advancements in the company’s ongoing clinical trials; the timing of data announcements related to ongoing clinical trials and the initiation of future clinical trials. Such forward-looking statements involve substantial risks and uncertainties that could cause Gritstone’s research and clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements, including interim results obtained may differ from those at completion of the studies and clinical trials. Such risks and uncertainties include, among others, the uncertainties inherent in the drug development process, including Gritstone’s programs’ early stage of development, the process of designing and conducting preclinical and clinical trials, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, Gritstone’s ability to successfully establish, protect and defend its intellectual property and other matters that could affect the sufficiency of existing cash to fund operations. Gritstone undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of the company in general, see Gritstone’s most recent Quarterly Report on Form 10-Q filed on
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