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Non-Small Cell Lung CancerPhase 1/2NCT03953235

A Study of a Personalized Cancer Vaccine Targeting Shared Neoantigens

A Phase 1/2 study testing GRT-C903, GRT-R904 and nivolumab in people with Non-Small Cell Lung Cancer and Colorectal Cancer, run by Gritstone bio, Inc. at 12 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to evaluate the dose, safety, immunogenicity and early clinical activity of GRT-C903 and GRT-R904, a neoantigen-based therapeutic cancer vaccine, in combination with immune checkpoint blockade, in patients with advanced or metastatic non-small cell lung cancer, microsatellite stable… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
GRT-C903, GRT-R904 and nivolumab
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
12 sitesUnited States
Study dates
18 Jul 2019to 10 Mar 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Provide a signed and dated informed consent form prior to initiation of study-specific procedures.
  • Patients with the indicated advanced or metastatic solid tumor as follows:
  • Microsatellite-stable colorectal cancer (MSS-CRC) who are currently receiving systemic treatment with a fluoropyrimidine and oxaliplatin and/or irinotecan that may include a VEGF or EGFR targeting therapy as their 1L therapy for metastatic disease OR who have experienced disease progression following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan that may include a VEGF or EGFR targeting therapy and have not received additional lines of systemic therapy in the metastatic setting.
  • Non-small cell lung cancer (NSCLC) who are currently receiving systemic treatment with an anti-PD-(L)1 antibody in combination with cytotoxic, platinum-based chemotherapy OR who have experienced disease progression following treatment with an anti-PD-(L)1 antibody in combination with cytotoxic, platinum-based chemotherapy (or anti-PD-(L)1 alone if patient refuses platinum-based chemotherapy), and have not received additional lines of systemic therapy in the metastatic setting.
  • Pancreatic ductal adenocarcinoma (PDA) who are currently receiving systemic cytotoxic chemotherapy as their 1L therapy for metastatic disease OR who have experienced disease progression on 1L systemic cytotoxic chemotherapy and have received no more than 1 prior line of therapy in the metastatic setting.
  • Any solid tumor histology where the patient has experienced disease progression with all available therapies known to confer clinical benefit
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  • Patient's tumor possesses one of the mutations listed below, and is determined to express a HLA allele for antigen presentation of the identified tumor mutation:
  • VERSION 1.0 of the expression cassette:
  • BRAFG466V // CTNNB1S37F // CTNNB1S45F // CTNNB1S45P // CTNNB1T41A // ERBB2Y772A775dup // KRASG12C or NRASG12C // KRASG12D or NRASG12D // KRASG12V // KRASG13D // KRASQ61H or NRASQ61H // KRASQ61K or NRASQ61K // KRASQ61L or NRASQ61L // KRASQ61R or NRASQ61R // TP53K132E // TP53K132N // TP53R213L // TP53R249M // TP53S127Y
  • VERSION 2.0 of the expression cassette:
  • KRASG12C or NRASG12C // KRASG12D or NRASG12D // KRASG12V or NRASG12V // KRASQ61H or NRASQ61H
  • ECOG Performance Status 0 or 1
  • Measurable disease according to RECIST v1.1
  • Adequate organ function, as measured by laboratory values (criteria listed in protocol)

Who cannot join

  • Tumors with genetic characteristics as follows:
  • For NSCLC, patients with a known genetic driver alteration in EGFR, ALK, ROS1, RET, or TRK
  • Patients with known MSI-high disease based on institutional standard
  • Known exposure to chimpanzee adenovirus or any history of anaphylaxis in reaction to a vaccination
  • Bleeding disorder (eg., factor deficiency, coagulopathy) or history of significant bruising or bleeding following IM injections or blood draws
  • History of allogenic/solid organ transplant
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  • Active, known, or suspected autoimmune disease
  • Active tuberculosis or recent (<2 week) clinically significant infection, or evidence of active hepatitis B or hepatitis C
  • Known history of positive test for human immunodeficiency (HIV) or known acquired immunodeficiency syndrome (AIDS)
  • Complete inclusion and exclusion criteria are listed in the clinical study protocol.

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites

  • University of Chicago Medicine, Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • The Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Virginia Cancer Specialists

    Fairfax, Virginia, 22031

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Mayo Clinic Florida

    Jacksonville, Florida, 32224

  • Tennessee Oncology

    Nashville, Tennessee, 37203

  • Columbia University Medical Center, Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Mayo Clinic Arizona

    Phoenix, Arizona, 85054

  • Mayo Clinic Rochester

    Rochester, Minnesota, 55905

  • UCLA Medical Center

    Santa Monica, California, 90404

Other trials in United States

About this study

Official title: A Phase 1/2 Study of GRT-C903/GRT-R904, a Vaccine Targeting Shared Neoantigens, in Combination With Immune Checkpoint Blockade for Patients With Advanced Solid Tumors

The purpose of this study is to evaluate the dose, safety, immunogenicity and early clinical activity of GRT-C903 and GRT-R904, a neoantigen-based therapeutic cancer vaccine, in combination with immune checkpoint blockade, in patients with advanced or metastatic non-small cell lung cancer, microsatellite stable colorectal cancer, pancreatic cancer, and shared neoantigen-positive tumors. Based on the Phase 1 data, an updated vaccine candidate (SLATE-KRAS or version 2) was developed that removed 16 of the 20 mutations included in the original vaccine (version 1) and solely targets KRAS mutations.

Read the detailed description

Tumors harboring non-synonymous deoxyribonucleic acid (DNA) mutations can present peptides containing these mutations as non-self antigens in the context of HLA on the tumor cell surface. A fraction of mutated peptides result in neoantigens capable of generating T-cell responses that exclusively target tumor cells. Some of these tumor-specific neoantigens are known or expected to be common across a subset of patients and are called shared neoantigens. This study aims to target shared neoantigens using a heterologous prime/boost therapeutic vaccine approach (GRT-C903 first followed by GRT-R904) in combination with checkpoint blockade to stimulate an immune response. This study will explore the safety and early clinical activity of this neoantigen-based immunotherapy intended to induce T-cell responses specific for the shared neoantigens contained within the therapeutic vaccine. Phase 1 will test multiple doses and combinations with checkpoint blockade and Phase 2 will test for early signs of clinical activity using a vaccine regimen based on Phase 1 data.

Being tested
GRT-C903, GRT-R904, nivolumab, ipilimumab
Keywords
neoantigen cancer vaccine, shared neoantigen, GRT-C903, GRT-R904, immunotherapy, PD-1, CTLA-4, nivolumab, ipilimumab
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Pancreatic Neoplasms, Diabetes Mellitus, Insulin-Dependent, 12

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GRT-C903Biological

    a shared neoantigen cancer vaccine prime

  • GRT-R904Biological

    a shared neoantigen cancer vaccine boost

  • nivolumabBiological

    anti-PD-1 monoclonal antibody

  • ipilimumabBiological

    anti-CTLA-4 monoclonal antibody

Study groups in NCT03953235
Study groupRoleWhat they receive
Phase 1Experimental* GRT-C903 * GRT-R904 * nivolumab * ipilimumab
Receives: Biological: GRT-C903; Biological: GRT-R904; Biological: nivolumab; Biological: ipilimumab
Phase 2Experimental* GRT-C903 * GRT-R904 * nivolumab * ipilimumab Phase 2 for some patients includes a monthly or every two month treatment schedule
Receives: Biological: GRT-C903; Biological: GRT-R904; Biological: nivolumab; Biological: ipilimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of adverse events (AEs), serious adverse events (SAEs), and dose limiting toxicities (DLTs)

    Measured: Initiation of study treatment through 100 days post-last dose (up to approximately 27 months)

  2. Objective Response Rate (ORR) in Phase 2 using RECIST v1.1

    Measured: Initiation of study treatment until disease progression (up to approximately 27 months)

  3. Identify the recommended Phase 2 dose (RP2D) of GRT-C903 and GRT-R904

    Measured: Up to approximately 6 months

Secondary outcomes (6)

  1. Measure the immune response to the neoantigens encoded by GRT-C903 and GRT-R904

    Measured: Baseline to end of treatment (up to approximately 12 months)

  2. Objective Response Rate (ORR) in Phase 1 using RECIST v1.1

    Measured: Initiation of study treatment until disease progression (up to approximately 27 months)

  3. Duration of response (DOR) using RECIST v1.1

    Measured: Initiation of study treatment until disease progression (up to approximately 27 months)

  4. Clinical benefit rate (CBR) using RECIST v1.1

    Measured: Initiation of study treatment until disease progression (up to approximately 27 months)

  5. Progression-free survival (PFS)

    Measured: Up to approximately 4 years

  6. Overall survival (OS)

    Measured: Up to approximately 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 May 2019
  2. Study start18 Jul 2019
  3. Primary completion10 Mar 2023
  4. Study completion10 Mar 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03953235
Sponsor's protocol ID
GO-005
Status last verified
Sep 2023
First submitted
14 May 2019
Last updated
13 Sep 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Rappaport AR, Kyi C, Lane M, Hart MG, Johnson ML, Henick BS, Liao CY, Mahipal A, Shergill A, Spira AI, Goldman JW, Scallan CD, Schenk D, Palmer CD, Davis MJ, Kounlavouth S, Kemp L, Yang A, Li YJ, Likes M, Shen A, Boucher GR, Egorova M, Veres RL, Espinosa JA, Jaroslavsky JR, Kraemer Tardif LD, Acrebuche L, Puccia C, Sousa L, Zhou R, Bae K, Hecht JR, Carbone DP, Johnson B, Allen A, Ferguson AR, Jooss K. A shared neoantigen vaccine combined with immune checkpoint blockade for advanced metastatic solid tumors: phase 1 trial interim results. Nat Med. 2024 Apr;30(4):1013-1022. doi: 10.1038/s41591-024-02851-9. Epub 2024 Mar 27.

    PubMed 38538867

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing GRT-C903, GRT-R904 and nivolumab in people with Non-Small Cell Lung Cancer and Colorectal Cancer, run by Gritstone bio, Inc. at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (AEs), serious adverse events (SAEs), and dose limiting toxicities (DLTs) (time frame: Initiation of study treatment through 100 days post-last dose (up to approximately 27 months)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03953235, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2023.

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