A Study of a Personalized Cancer Vaccine Targeting Shared Neoantigens

• Sponsor: Gritstone bio, Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT03953235
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 144
• Locations: 13
• Arms: 2
• Anticipated Duration (Months): 52.5
• Patients Per Site: 11.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief 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 colorectal cancer, pancreatic cancer, and shared neoantigen-positive tumors.

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer; Colorectal Cancer; Pancreatic Cancer; Solid Tumor; Shared Neoantigen-Positive Solid Tumors	Biological: GRT-C903; Biological: GRT-R904; Biological: nivolumab; Biological: ipilimumab	Phase 1/Phase 2

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 144 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Jul 18, 2019
• Anticipated Primary Completion Date: Dec 1, 2022
• Anticipated Study Completion Date: Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1 GRT-C903 GRT-R904 nivolumab ipilimumab	Biological: GRT-C903; a shared neoantigen cancer vaccine prime; Biological: GRT-R904; a shared neoantigen cancer vaccine boost; Biological: nivolumab; anti-PD-1 monoclonal antibody; Biological: ipilimumab; anti-CTLA-4 monoclonal antibody
Experimental: Phase 2 GRT-C903 GRT-R904 nivolumab ipilimumab	Biological: GRT-C903; a shared neoantigen cancer vaccine prime; Biological: GRT-R904; a shared neoantigen cancer vaccine boost; Biological: nivolumab; anti-PD-1 monoclonal antibody; Biological: ipilimumab; anti-CTLA-4 monoclonal antibody

Outcome Measures

Primary Outcome Measures

1. Incidence of adverse events (AEs), serious adverse events (SAEs), and dose limiting toxicities (DLTs) [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 [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 [Up to approximately 6 months]

Secondary Outcome Measures

1. Measure the immune response to the neoantigens encoded by GRT-C903 and GRT-R904 [Baseline to end of treatment (up to approximately 12 months)]

2. Objective Response Rate (ORR) in Phase 1 using RECIST v1.1 [Initiation of study treatment until disease progression (up to approximately 27 months)]

3. Duration of response (DOR) using RECIST v1.1 [Initiation of study treatment until disease progression (up to approximately 27 months)]

4. Clinical benefit rate (CBR) using RECIST v1.1 [Initiation of study treatment until disease progression (up to approximately 27 months)]

5. Progression-free survival (PFS) [Up to approximately 4 years]

6. Overall survival (OS) [Up to approximately 4 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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:

1. 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.

2. 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.

3. 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.

4. Any solid tumor histology where the patient has experienced disease progression with all available therapies known to confer clinical benefit

• 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:

BRAF_G466V // CTNNB1_S37F // CTNNB1_S45F // CTNNB1_S45P // CTNNB1_T41A // ERBB2_Y772_A775dup // KRAS_G12C or NRAS_G12C // KRAS_G12D or NRAS_G12D // KRAS_G12V // KRAS_G13D // KRAS_Q61H or NRAS_Q61H // KRAS_Q61K or NRAS_Q61K // KRAS_Q61L or NRAS_Q61L // KRAS_Q61R or NRAS_Q61R // TP53_K132E // TP53_K132N // TP53_R213L // TP53_R249M // TP53_S127Y

• 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)

Exclusion Criteria:

• Tumors with genetic characteristics as follows:

1. For NSCLC, patients with a known genetic driver alteration in EGFR, ALK, ROS1, RET, or TRK

2. 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

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Arizona	Phoenix	Arizona	United States	85054
2	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
3	UCLA Medical Center	Santa Monica	California	United States	90404
4	Mayo Clinic Florida	Jacksonville	Florida	United States	32224
5	University of Chicago Medicine, Comprehensive Cancer Center	Chicago	Illinois	United States	60637
6	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
7	Mayo Clinic Rochester	Rochester	Minnesota	United States	55905
8	Columbia University Medical Center, Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
9	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
10	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
11	Tennessee Oncology	Nashville	Tennessee	United States	37203
12	MD Anderson Cancer Center	Houston	Texas	United States	77030
13	Virginia Cancer Specialists	Fairfax	Virginia	United States	22031

Sponsors and Collaborators

• Gritstone bio, Inc.
• Bristol-Myers Squibb

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gritstone bio, Inc.
• ClinicalTrials.gov Identifier: NCT03953235
• Other Study ID Numbers: GO-005
• First Posted: May 16, 2019
• Last Update Posted: Sep 11, 2020
• Last Verified: Sep 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Gritstone bio, Inc.: neoantigen cancer vaccine; shared neoantigen; GRT-C903; GRT-R904; immunotherapy; PD-1; CTLA-4; nivolumab; ipilimumab
• Additional relevant MeSH terms: Neoplasms; Nivolumab; Ipilimumab

Study Results

No Results Posted as of Sep 11, 2020