A Study of a Personalized Neoantigen Vaccine in Combination With Immune Checkpoint Blockade for Patients With Metastatic Colorectal Cancer

Sponsor

Gritstone bio, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05141721

Collaborator

(none)

665

Enrollment

Locations

Arms

60.6

Anticipated Duration (Months)

17.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

Anticipated 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 :

Feb 12, 2022

Anticipated Primary Completion Date :

Mar 1, 2027

Anticipated Study Completion Date :

Mar 1, 2027

Arms and Interventions

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 Names: 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 Names: Yervoy Drug: Fluoropyrimidine Fluoropyrimidine administered as maintenance therapy per standard of care. Drug: Bevacizumab Bevacizumab administered as maintenance therapy per standard of care. Other Names: Avastin Drug: Oxaliplatin Oxaliplatin administered as induction therapy per standard of care. Other Names: 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 Names: Avastin Drug: Oxaliplatin Oxaliplatin administered as induction therapy per standard of care. Other Names: Eloxatin

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 Names:

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 Names:

Yervoy

Drug: Fluoropyrimidine

Fluoropyrimidine administered as maintenance therapy per standard of care.

Drug: Bevacizumab

Bevacizumab administered as maintenance therapy per standard of care.

Other Names:

Avastin

Drug: Oxaliplatin

Oxaliplatin administered as induction therapy per standard of care.

Other Names:

Eloxatin

Active Comparator: Control Arm

Drug: Fluoropyrimidine

Fluoropyrimidine administered as maintenance therapy per standard of care.

Drug: Bevacizumab

Bevacizumab administered as maintenance therapy per standard of care.

Other Names:

Avastin

Drug: Oxaliplatin

Oxaliplatin administered as induction therapy per standard of care.

Other Names:

Eloxatin

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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 [Phase 2 up to 27 months, Phase 3 up to 60 months]
Phase 2 and 3: Progression-free Survival per RECIST v1.1 and iRECIST as assessed by the investigator [From time of randomization until disease progression or death from any cause (Phase 2: up to 27 months, Phase 3: up to 60 months)]
Phase 3: Progression-free Survival per RECIST v1.1 as assessed by blinded IRC [From time of randomization until disease progression or death from any cause (up to 60 months)]
Phase 2 and 3: Overall Survival [Phase 2 up to 27 months, Phase 3 up to 60 months]
Phase 2 and 3: Overall Response Rate [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.
Phase 2 and 3: Duration of Response [From time of first response until disease progression (Phase 2 up to 27 months, Phase 3 up to 60 months)]
Phase 2 and 3: Clinical Benefit Rate (CBR) [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.
Phase 2 and 3: Deepening of Response [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.
Phase 2 and 3: Success of Vaccine Manufacture [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Banner MD Anderson	Gilbert	Arizona	United States	85234
3	Highlands Oncology	Springdale	Arkansas	United States	72762
4	U.S.C Norris Cancer Center, Keck School of Medicine, Division of Medical Oncology	Los Angeles	California	United States	90033
5	University of California - Irvine (UCI)	Orange	California	United States	92697
6	University of California Los Angeles (UCLA)	Santa Monica	California	United States	90404
7	Eastern CT Hematology and Oncology Associates (ECHO)	Norwich	Connecticut	United States	06360
8	Lynn Cancer Institute - Boca Raton Regional Hospital	Boca Raton	Florida	United States	33486
9	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida	United States	33140
10	University of Miami	Miami	Florida	United States	33136
11	Miami Cancer Institute at Baptist Health South Florida (USOR site)	Miami	Florida	United States	33176
12	Orlando Health	Orlando	Florida	United States	32806
13	Advanced Research (Oncology & Hemotology Associates of West Broward)	Tamarac	Florida	United States	33321
14	University of Illinois at Chicago	Chicago	Illinois	United States	60607
15	Rush University Medical Center	Chicago	Illinois	United States	60612
16	University of Chicago	Chicago	Illinois	United States	60637
17	Indiana University	Indianapolis	Indiana	United States	46202
18	American Oncology Partners of Maryland, PA	Bethesda	Maryland	United States	20817
19	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201
20	Astera Cancer Care	East Brunswick	New Jersey	United States	08816
21	Summit Health	Florham Park	New Jersey	United States	07932
22	Morristown Medical Center	Morristown	New Jersey	United States	07960
23	Rutgers	New Brunswick	New Jersey	United States	08903
24	NYU Langone Health	New York	New York	United States	10016
25	Columbia University Irving Medical Center	New York	New York	United States	10032
26	New York Cancer and Blood	Port Jefferson Station	New York	United States	11776
27	Carolinas Center For Advanced Management of Pain	Pinehurst	North Carolina	United States	28370
28	Christ Hospital Cancer Center	Cincinnati	Ohio	United States	45229
29	Sidney Kimmel Medical College at Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
30	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
31	Tennessee Oncology - Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
32	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
33	MD Anderson	Houston	Texas	United States	77030
34	Baylor Scott and White	Temple	Texas	United States	76508
35	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah	United States	84112
36	University of Virginia	Charlottesville	Virginia	United States	22903
37	Virginia Cancer Specialists	Fairfax	Virginia	United States	22031
38	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226