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Gritstone bio Announces Positive Preliminary Progression-free Survival and Long-term Circulating Tumor DNA (ctDNA) Data from Phase 2 Portion of Ongoing Phase 2/3 Study of its Personalized Cancer Vaccine, GRANITE, in Front-line Metastatic Microsatellite Stable Colorectal Cancer (MSS-CRC)

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Gritstone bio, Inc. (Nasdaq: GRTS) announces positive preliminary data from Phase 2 study of GRANITE, a personalized neoantigen cancer vaccine, in metastatic colorectal cancer patients. Early PFS trends show benefit for GRANITE recipients, with a high-risk group showing a 48% relative risk reduction in progression or death. Mature PFS data expected in Q3 2024 and overall survival data in 1H 2025.
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The preliminary data from Gritstone bio's Phase 2 study on GRANITE, a personalized neoantigen cancer vaccine, is indeed promising, particularly for metastatic microsatellite stable colorectal cancer (MSS-CRC), a variant notoriously resistant to conventional immunotherapies. The progression-free survival (PFS) trends indicate a potential shift in treatment paradigms for a disease that has limited options once it becomes metastatic. The hazard ratios (HR) reported suggest a reduction in the risk of disease progression or death, especially notable in high-risk patients with liver metastases. The correlation between long-term circulating tumor DNA (ctDNA) responses and PFS is an important indicator of the vaccine's potential efficacy.

From a research standpoint, the 100% vaccine manufacturing success rate is a technical triumph, ensuring that the study's validity is not compromised by production issues. This aspect also highlights the company's capability to scale up personalized medicine, which is a complex process. However, the admission of an uninformative short-term molecular response due to an unexpectedly persistent ctDNA drop post-chemotherapy is a reminder of the challenges in defining biomarkers for immunotherapy response. This could influence future study designs and the interpretation of early data in similar trials.

Considering the long-term implications, if the mature PFS data expected in Q3 2024 and overall survival data expected in the first half of 2025 confirm these preliminary findings, there could be a substantial impact on the standard of care for MSS-CRC patients. The potential for a Phase 3 trial would be a significant step forward, not just for Gritstone bio but for the field of oncology, as it would validate the role of personalized vaccines in treating 'cold' tumors that are less likely to respond to immunotherapies.

The biotechnology sector is highly driven by clinical trial outcomes, which Gritstone bio's GRANITE vaccine has just influenced. The early positive results are likely to be well-received by investors, as they represent a breakthrough in a difficult-to-treat cancer. The stock market typically reacts to such news with optimism, potentially increasing Gritstone bio's market valuation. However, investors should take note of the fact that the data is still preliminary and the confidence intervals are wide, indicating uncertainty in the results.

Moreover, the successful manufacturing rate is a positive indicator not only of the company's technical expertise but also of its potential to deliver on personalized therapies at scale, which could be a significant competitive advantage. The financial implications of this could be considerable, as personalized medicine commands a premium price in the market. Yet, the cost of goods sold (COGS) and logistics for such tailored treatments are typically higher, which will need to be factored into the company's financial modeling.

Looking ahead, the mature PFS data and overall survival data will be critical milestones that could further influence the company's stock performance. Positive results could lead to a surge in investor confidence and potentially partnerships or buyout offers. Conversely, disappointing results could have a detrimental effect. Investors should keep a close eye on these developments and consider the long-term potential alongside the inherent risks of clinical trials.

The MSS-CRC market segment represents a significant unmet medical need and the preliminary data suggesting efficacy of GRANITE in this space could have profound market implications. Currently, the options for patients with MSS-CRC are limited and a successful vaccine could disrupt existing treatment protocols. If the vaccine progresses to a Phase 3 trial and eventually gains regulatory approval, it could capture a sizable market share and potentially redefine the standard of care for this patient population.

From a market perspective, the ability to address 'cold' tumors, which traditionally have not responded well to immunotherapies, could open up new therapeutic categories and expand the addressable market for immunotherapies. This would not only benefit Gritstone bio but could also stimulate further innovation and competition in the biotech industry, leading to a dynamic shift in the oncology market landscape.

However, the route from Phase 2 to market success is fraught with challenges, including regulatory hurdles, market adoption and reimbursement issues. The long-term market impact will depend on the final clinical trial results, regulatory approval and the company's ability to market and distribute the vaccine effectively. Stakeholders should monitor how Gritstone bio navigates these challenges and the subsequent market response to gauge the full potential impact.

-- Early progression-free survival (PFS) trends favor GRANITE recipients with hazard ratios of 0.82 in the overall population ([95% CI, 0.34-1.67]; 62% censored) and 0.52 (48% relative risk reduction of progression or death with GRANITE vs. control) in a high-risk group, where clinical data are more mature ([95% CI, 0.15-1.38]; 44% censored); >90% of high-risk patients have liver metastases --

-- Short-term molecular response (as defined by protocol) is uninformative due to an unexpectedly persistent ctDNA drop beyond induction chemotherapy; long-term circulating tumor DNA (ctDNA) responses align with PFS trends and favor GRANITE vs. control patients --

-- GRANITE was generally well-tolerated with manageable adverse events; no patients have discontinued GRANITE due to adverse events --

-- Mature PFS data expected in the third quarter of 2024; overall survival data expected in 1H 2025 --

EMERYVILLE, Calif., April 01, 2024 (GLOBE NEWSWIRE) -- Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company working to develop the world’s most potent vaccines, today announced positive preliminary data from the ongoing, signal seeking Phase 2 portion of the Phase 2/3 study evaluating GRANITE, its personalized neoantigen cancer vaccine, in front-line metastatic microsatellite stable colorectal cancer (MSS-CRC). The randomized, controlled, open-label study is designed to quantify the clinical benefit of maintenance therapy with GRANITE (GRT-C901/GRT-R902) in combination with immune checkpoint blockade in addition to fluoropyrimidine/bevacizumab versus fluoropyrimidine/bevacizumab alone. Overall progression free survival (PFS) data show an early trend in benefit for GRANITE patients (HR=0.82, [95% CI, 0.34-1.67]; 62% censored) and extended PFS benefit in high-risk patients (HR=0.52 [95% CI, 0.15-1.38]; 44% censored), in whom progression occurs faster. Circulating tumor DNA (ctDNA) analysis over several months of treatment shows the expected relationship with disease progression and favors GRANITE, while short-term ctDNA response analysis (molecular response as defined per protocol) did not demonstrate a difference between study arms. Gritstone bio successfully manufactured GRANITE product candidate for every eligible patient (i.e., 100% vaccine manufacturing success rate).

“Today's preliminary Phase 2 results are highly encouraging and represent the first randomized trial evidence, albeit early, that a personalized neoantigen-directed vaccine can potentially drive efficacy in a metastatic ‘cold’ tumor. The overall trend of PFS improvement in GRANITE recipients is great to see, and the exploratory PFS hazard ratio of 0.52 in the high-risk group, a more mature dataset, is a striking signal,” said Andrew Allen, MD, PhD, Co-founder, President & CEO of Gritstone bio. “Pioneering new spaces carries inherent risks, and with regard to defining molecular response, we simply got it wrong. ctDNA levels in both arms decreased on chemotherapy for longer than we anticipated, generating similar short-term molecular response rates across arms and rendering our protocol measure of ctDNA change uninformative. Fortunately, long-term analysis demonstrates the expected correlation of ctDNA with clinical benefit and favors GRANITE patients. We believe these preliminary findings put us in a strong position to share mature PFS data in the third quarter and then enter regulatory discussions regarding Phase 3. The growing body of evidence favoring GRANITE in this trial, including positive PFS and long-term ctDNA trends in both high and low-risk populations, is exciting and suggests GRANITE is working in this notoriously underserved patient population.”

“Up to 97% of patients with metastatic colorectal cancer, the second most common cause of cancer death, are MSS. Unlike patients with melanoma and lung cancer, they have not benefited from standard immunotherapies such as checkpoint inhibitors. These preliminary results indicate that GRANITE is inducing a potentially significant immune response in a disease that has been felt to be immunologically cold,” said J. Randolph Hecht, MD, Professor of Clinical Medicine and Director of the UCLA GI Oncology Program and an investigator in the GRANITE Phase 2/3 study. “The PFS difference, particularly in a poor prognosis group of patients, indicates the potential for clinical benefit and provides the rationale for a confirmatory Phase 3 trial, about which I am very excited. Furthermore, we are learning how to better analyze ctDNA continuously to study the efficacy of this novel immunotherapy. Expanding the scope of immunotherapy to a broader spectrum of cancer patients is the ‘holy grail’ of oncology, especially for MSS colorectal cancer. While early, these promising results suggest GRANITE has potential to deliver clinically meaningful benefit in MSS-CRC and other cold tumors.”

Key Findings from Preliminary Phase 2 Data in Front-Line Metastatic MSS-CRC
Clinical data cut as of March 8, 2024; ctDNA data cut as of March 12, 2024

One hundred and four (104) patients were randomized (1:1) in the study: Sixty-seven (67) patients (39 GRANITE arm, 28 control arm) are included in the treated analysis below. Thirty-six patients have left the study prior to randomized treatment primarily due to early progressive disease or withdrawal of consent, and one patient has yet to begin study treatment start. Demographics and clinical characteristics were balanced between arms (stage, sidedness, presence of liver metastases), with approximately 75% of patients having liver metastases.

Progression Free Survival (PFS)

  • Early trend in PFS benefit was observed for GRANITE recipients
    • Hazard ratio of 0.82 ([95% CI, 0.34-1.67]; 62% censored) in all patients
    • Hazard ratio of 0.52 ([95% CI, 0.15-1.38]; 44% censored) in high-risk patients1 (>90% have liver metastases). Median PFS of 12 months (GRANITE) vs. 7 months (control).
      • 1High-risk subgroup defined as baseline ctDNA above the median value (2%) for the control group (ctDNA quantified as mean variant allele frequency [VAF] at time of study randomization). This analysis was performed on 44 patients who received study treatment (control and GRANITE arms) and have available baseline ctDNA data.
    • GRANITE and control arms begin separating 1-2 months after initiation of GRANITE treatment, consistent with expected kinetics of GRANITE-induced immune response

Biomarker Results – Circulating Tumor DNA (ctDNA)

  • Short-term molecular response (>30% reduction in ctDNA using single time-point analysis, defined per protocol) is uninformative due to unanticipated continuation of ctDNA drop beyond induction chemotherapy.
    • Molecular response, similar in both arms (30% [6/20] in vaccine arm; 42% [5/12] in control arm)
  • Long-term ctDNA responses align with PFS trends and favor GRANITE vs. control patients
    • Analysis in the high-risk group1 shows that between first blood draw (time of randomization) and last blood draw (most recent study visit), ctDNA shifted from high (>2% VAF) to low (≤2% VAF) in 56% (9/16) of GRANITE patients vs 22% (2/9) of control patients. Progressive disease was observed in 44% (7/16) vs 78% (7/9), respectively, within this group.
    • Analysis in patients whose ctDNA was negative after induction chemotherapy, a low-risk group, favors GRANITE. Sustained ctDNA negativity was observed in 67% (6/9) of GRANITE recipients vs 38% (3/8) control patients. Progressive disease was observed in 11% (1/9) and 38% (3/8) of these patients, respectively.

Safety and Tolerability

  • GRANITE demonstrated a favorable safety and tolerability profile
    • Vast majority of adverse events (AEs) were Grade 1/2
    • Common AEs were mild systemic and local effects typically associated with any potent vaccine (i.e., transient flu-like illness)
    • No patients discontinued study treatment due to an AE

A presentation reviewing these results has been added to the Presentations page of Gritstone’s website, https://ir.gritstonebio.com/investors/presentations.

About Gritstone bio
Gritstone bio, Inc. (Nasdaq: GRTS) is a clinical-stage biotechnology company that aims to develop the world’s most potent vaccines. We leverage our innovative vectors and payloads to train multiple arms of the immune system to attack critical disease targets. Independently and with our collaborators, we are advancing a portfolio of product candidates to treat and prevent viral diseases and solid tumors in pursuit of improving patient outcomes and eliminating disease. www.gritstonebio.com

Gritstone Forward-Looking Statements
This press release contains forward-looking statements, including, but not limited to, statements related to our clinical and regulatory development plans for our product candidates; our expectations regarding the data to be derived in our ongoing and planned clinical trials, including, the preliminary nature of the data disclosed in this press release and potential for such data to change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data; the timing of commencement and results of our future nonclinical studies, clinical trials and research and development programs; our ability to discover, develop and advance product candidates into, and successfully complete, clinical trials (including the timing of our expected PFS and OS data readout); and our plans and strategy regarding maintaining existing and entering into new collaborations and/or partnerships. Such forward-looking statements involve substantial risks and uncertainties that could cause Gritstone bio’s research and clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the drug development process, including Gritstone bio’s programs’ clinical 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 product candidates, Gritstone bio’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 bio 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 bio’s most recent Annual Report on Form 10-K filed on March 5, 2024 and any subsequent current and periodic reports filed with the Securities and Exchange Commission.

Gritstone Contacts
Investors:
George E. MacDougall
Gritstone bio, Inc.
ir@gritstone.com

Media:
Dan Budwick
1AB
(973) 271-6085
dan@1abmedia.com


FAQ

What is the ticker symbol of Gritstone bio, Inc.?

The ticker symbol of Gritstone bio, Inc. is GRTS.

What type of cancer is being studied in the Phase 2 trial of GRANITE?

The Phase 2 trial of GRANITE is studying metastatic microsatellite stable colorectal cancer (MSS-CRC).

What are the early progression-free survival (PFS) trends favoring GRANITE recipients?

The early PFS trends show a hazard ratio of 0.82 in the overall population and 0.52 in a high-risk group, with a 48% relative risk reduction in progression or death.

When are mature PFS data expected for the GRANITE study?

Mature PFS data are expected in the third quarter of 2024.

What are the overall survival data expected for the GRANITE study?

Overall survival data are expected in the first half of 2025.

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About GRTS

gritstone oncology is a cancer immunotherapy company developing next-generation personalized cancer therapeutics. gritstone brings together distinguished scientific founders, an experienced and diverse management team, a seasoned and successful board of directors, and very deep financial backing to tackle fundamental challenges at the intersection of cancer biology, immunology, and immunotherapy design. the company’s initial goal is to identify and deploy therapeutic neo-antigens from individual patients’ tumors to develop novel treatments for lung cancer. gritstone oncology is headquartered in the san francisco bay area with certain key functions located in cambridge, ma. gritstone oncology launched in october 2015 with a series a financing of $102 million.