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Trial record 1 of 1 for:    NCT05141721
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A Study of a Personalized Neoantigen Vaccine in Combination With Immune Checkpoint Blockade for Patients With Metastatic Colorectal Cancer

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ClinicalTrials.gov Identifier: NCT05141721
Recruitment Status : Recruiting
First Posted : December 2, 2021
Last Update Posted : October 28, 2022
Sponsor:
Information provided by (Responsible Party):
Gritstone bio, Inc.

Brief Summary:
The primary objective of the Phase 2 portion of the study is to characterize the clinical activity of maintenance therapy with GRT-C901/GRT-R902 in combination with checkpoint inhibitors in addition to fluoropyrimidine/bevacizumab versus fluoropyrimidine/bevacizumab alone as assessed by changes in circulating tumor (ct)DNA. The primary objective of the Phase 3 portion is to demonstrate clinical efficacy of the regime as assessed by progression-free survival.

Condition or disease Intervention/treatment Phase
Colorectal Neoplasms Drug: GRT-C901 Drug: GRT-R902 Drug: Atezolizumab Drug: Ipilimumab Drug: Fluoropyrimidine Drug: Bevacizumab Drug: Oxaliplatin Phase 2 Phase 3

Detailed Description:
Tumors harboring non-synonymous deoxyribonucleic acid (DNA) mutations can present peptides containing these mutations as non-self antigens in the context of human leukocyte antigens (HLAs) on the tumor cell surface. A fraction of mutated peptides result in neoantigens capable of generating T-cell responses that exclusively target tumor cells. Sensitive detection of these mutations allows for the identification of neoantigens unique to each patient's tumor to be included in a personalized cancer vaccine that targets these neoantigens. This vaccine regimen uses two vaccine vectors as a heterologous prime/boost approach (GRT-C901 first followed by GRT-R902) to stimulate an immune response. This study will explore the anti-tumor activity of this patient-specific immunotherapy in combination with checkpoint inhibitors in addition to fluoropyrimidine/bevacizumab.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 665 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2/3, Randomized, Open-Label Study of Maintenance GRT-C901/GRT-R902, A Neoantigen Vaccine, in Combination With Immune Checkpoint Blockade for Patients With Metastatic Colorectal Cancer
Actual Study Start Date : February 12, 2022
Estimated Primary Completion Date : March 2027
Estimated Study Completion Date : March 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vaccines

Arm Intervention/treatment
Experimental: Vaccine Arm
After receiving up to 24 weeks induction therapy with fluoropyrimidine/oxaliplatin/bevacizumab standard of care and undergoing vaccine production screening, patients will receive a total of 6 administrations of GRT-C901/GRT-R902 plus ipilimumab co-administered only with the first dose of GRT-C901 and GRT-R902. All patients will receive atezolizumab in addition to maintenance therapy of fluoropyrimidine and bevacizumab according to standard of care.
Drug: GRT-C901
A patient-specific neoantigen cancer vaccine administered via intramuscular (IM) injection as prime and single boost.

Drug: GRT-R902
A patient-specific neoantigen cancer vaccine boost, administered via IM injection.

Drug: Atezolizumab
Atezolizumab will be administered via intravenous infusion at a dose of 1680 mg once every 4 weeks.
Other Name: Tecentriq

Drug: Ipilimumab
Ipilimumab will be administered via subcutaneous injection at a dose of 30 mg with the first dose of GRT-C901 and GRT-R902.
Other Name: Yervoy

Drug: Fluoropyrimidine
Fluoropyrimidine administered as maintenance therapy per standard of care.

Drug: Bevacizumab
Bevacizumab administered as maintenance therapy per standard of care.
Other Name: Avastin

Drug: Oxaliplatin
Oxaliplatin administered as induction therapy per standard of care.
Other Name: Eloxatin

Active Comparator: Control Arm
After receiving up to 24 weeks induction therapy with fluoropyrimidine/oxaliplatin/bevacizumab standard of care and undergoing vaccine production screening, patients will receive maintenance therapy of fluoropyrimidine and bevacizumab according to standard of care.
Drug: Fluoropyrimidine
Fluoropyrimidine administered as maintenance therapy per standard of care.

Drug: Bevacizumab
Bevacizumab administered as maintenance therapy per standard of care.
Other Name: Avastin

Drug: Oxaliplatin
Oxaliplatin administered as induction therapy per standard of care.
Other Name: Eloxatin




Primary Outcome Measures :
  1. Phase 2: Antitumor activity measured by number of patients with ≥50% decrease from baseline in circulating tumor DNA (ctDNA) [ Time Frame: Baseline and up to 27 months ]
  2. Phase 3: Progression-free Survival per Immune-based Response Evaluation Criteria in Solid Tumors (iRECIST) as assessed by blinded independent review committee (IRC) [ Time Frame: From time of randomization until disease progression or death from any cause (up to 60 months) ]

Secondary Outcome Measures :
  1. Phase 2 and 3: Incidence of adverse events (AEs), immune-related AEs, treatment-related AEs, serious AEs, AEs leading to death, AEs leading to dose delays, and AEs leading to discontinuation of study treatment [ Time Frame: Phase 2 up to 27 months, Phase 3 up to 60 months ]
  2. Phase 2 and 3: Progression-free Survival per RECIST v1.1 and iRECIST as assessed by the investigator [ Time Frame: From time of randomization until disease progression or death from any cause (Phase 2: up to 27 months, Phase 3: up to 60 months) ]
  3. Phase 3: Progression-free Survival per RECIST v1.1 as assessed by blinded IRC [ Time Frame: From time of randomization until disease progression or death from any cause (up to 60 months) ]
  4. Phase 2 and 3: Overall Survival [ Time Frame: Phase 2 up to 27 months, Phase 3 up to 60 months ]
  5. Phase 2 and 3: Overall Response Rate [ Time Frame: Phase 2 up to 27 months, Phase 3 up to 60 months ]
    Response measured by number of patients with best response of Partial Response (PR), immune-base PR (iPR), Complete Response (CR), or iCR.

  6. Phase 2 and 3: Duration of Response [ Time Frame: From time of first response until disease progression (Phase 2 up to 27 months, Phase 3 up to 60 months) ]
  7. Phase 2 and 3: Clinical Benefit Rate (CBR) [ Time Frame: Phase 2 up to 27 months, Phase 3 up to 60 months ]
    CBR measured by number of patients who have achieved Stable Disease (SD), iSD, PR, iPR, CR, or iCR.

  8. Phase 2 and 3: Deepening of Response [ Time Frame: From time of first response (SD or PR) until conversion to PR or CR (Phase 2 up to 27 months, Phase 3 up to 60 months) ]
    Deepening of response measured by number of patients with SD or better response to routine therapy who convert from SD to PR or from PR to CR.

  9. Phase 2 and 3: Success of Vaccine Manufacture [ Time Frame: Study Treatment Screening visit (up to 28 days before Day 1 of study drug administration) ]
    Vaccine manufacture success measured by the number of patients having sufficient neoantigens identified to warrant vaccine production.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with histologically confirmed metastatic colorectal cancer (CRC) who are planned for, or have received no more than 1 cycle of first-line treatment in the metastatic setting with a fluoropyrimidine and oxaliplatin in combination with bevacizumab
  • Measurable and unresectable disease according to RECIST v1.1
  • Availability of formalin-fixed paraffin-embedded (FFPE) tumor specimens.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Patient has adequate organ function in opinion of investigator
  • If women of childbearing potential (WCBP), must be willing to undergo pregnancy testing and agrees to the use at least 1 highly effective contraceptive method during the study treatment period and for 150 days after last investigational study treatment.

Exclusion Criteria:

  • Patients with deficient mismatch repair (dMMR) or high levels of microsatellite instability (MSI-H) phenotype
  • Patient has a known tumor mutation burden <1 non-synonymous mutations/megabase
  • Known DNA Polymerase Epsilon mutations
  • Patients with known BRAFV600E mutations
  • Bleeding disorder or history of significant bruising or bleeding following IM injections or blood draws
  • Immunosuppression anticipated at time of study treatment
  • History of allogeneic tissue/solid organ transplant
  • Active or history of autoimmune disease or immune deficiency
  • Patient with symptomatic or actively progressing central nervous system (CNS) metastases, carcinomatous meningitis, or has been treated with whole brain radiation
  • History of other cancer within 2 years with the exception of neoplasm that has undergone potentially curative therapy
  • Any severe concurrent non-cancer disease that, in the judgment of the Investigator, would make the patient inappropriate for the current study
  • Active tuberculosis or recent (<2 weeks) clinically significant infection, evidence of active hepatitis B or hepatitis C, or known history of positive test for HIV
  • History of pneumonitis requiring systemic steroids for treatment (with the exception of prior resolved in-field radiation pneumonitis)
  • Myocardial infarction within previous 3 months, unstable angina, serious uncontrolled cardiac arrhythmia, history of myocarditis, or congestive heart failure
  • Pregnant, planning to become pregnant, or nursing.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05141721


Locations
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Sponsors and Collaborators
Gritstone bio, Inc.
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Responsible Party: Gritstone bio, Inc.
ClinicalTrials.gov Identifier: NCT05141721    
Other Study ID Numbers: GO-010
First Posted: December 2, 2021    Key Record Dates
Last Update Posted: October 28, 2022
Last Verified: September 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gritstone bio, Inc.:
Colorectal cancer vaccine
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Ipilimumab
Oxaliplatin
Atezolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action