Study of an Individualized Vaccine Targeting Neoantigens in Combination With Immune Checkpoint Blockade for Patients With Colon Cancer

Phase 2

Withdrawn

• Conditions: Colonic Neoplasms; Colorectal Neoplasms
• Interventions: Drug: GRT-C901; Drug: GRT-R902; Drug: Atezolizumab; Drug: Ipilimumab; Drug: Adjuvant chemotherapy

• Registration Number: NCT05456165
• Lead Sponsor: Gritstone bio, Inc.

Brief Summary

The primary objective is to assess and characterize the antitumor activity and safety and tolerability of adjuvant treatment with an individualized neoantigen vaccine called GRT-C901/GRT-R902 (chimpanzee adenovirus \[ChAd\] and self-amplifying messenger RNA \[samRNA\] vectors), in combination with checkpoint inhibitors. Antitumor activity will be based on molecular response in patients with colon cancer who have circulating tumor deoxyribonucleic acid (ctDNA) following surgical resection.

Detailed Description

Tumors harboring non-synonymous deoxyribonucleic acid (DNA) mutations 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 results 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, ChAd as prime and GRT-R902, samRNA as boost) to stimulate an immune response. This study (GRANITE-ADJUVANT) will explore the anti-tumor activity of this individualized, patient specific immunotherapy in combination with checkpoint inhibitors.

Study Timeline

• Study Start: 2022-05-19
• Study First Submitted: 2022-07-08
• Study First Submitted QC: 2022-07-08
• Study First Posted: 2022-07-13
• Primary Completion: 2022-09-01
• Study Completion: 2022-09-01
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-30
• Last Update Posted: 2024-12-31

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: 1

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GRT-C901/GRT-R902 Vaccine arm	GRT-C901	After surgical resection, patients who are circulating tumor DNA (ctDNA) positive will receive adjuvant chemotherapy for 12-24 weeks during which they will undergo neoantigen prediction, randomization, and vaccine manufacturing. After study treatment screening, patients who are still ctDNA positive with no evidence of residual or metastatic disease will receive a total of 6 doses of GRT-C901/ GRT-R902, 2 doses of ipilimumab, and 13 doses of atezolizumab. Study visits occur every 28 days.
GRT-C901/GRT-R902 Vaccine arm	GRT-R902	After surgical resection, patients who are circulating tumor DNA (ctDNA) positive will receive adjuvant chemotherapy for 12-24 weeks during which they will undergo neoantigen prediction, randomization, and vaccine manufacturing. After study treatment screening, patients who are still ctDNA positive with no evidence of residual or metastatic disease will receive a total of 6 doses of GRT-C901/ GRT-R902, 2 doses of ipilimumab, and 13 doses of atezolizumab. Study visits occur every 28 days.
GRT-C901/GRT-R902 Vaccine arm	Atezolizumab	After surgical resection, patients who are circulating tumor DNA (ctDNA) positive will receive adjuvant chemotherapy for 12-24 weeks during which they will undergo neoantigen prediction, randomization, and vaccine manufacturing. After study treatment screening, patients who are still ctDNA positive with no evidence of residual or metastatic disease will receive a total of 6 doses of GRT-C901/ GRT-R902, 2 doses of ipilimumab, and 13 doses of atezolizumab. Study visits occur every 28 days.
GRT-C901/GRT-R902 Vaccine arm	Ipilimumab	After surgical resection, patients who are circulating tumor DNA (ctDNA) positive will receive adjuvant chemotherapy for 12-24 weeks during which they will undergo neoantigen prediction, randomization, and vaccine manufacturing. After study treatment screening, patients who are still ctDNA positive with no evidence of residual or metastatic disease will receive a total of 6 doses of GRT-C901/ GRT-R902, 2 doses of ipilimumab, and 13 doses of atezolizumab. Study visits occur every 28 days.
GRT-C901/GRT-R902 Vaccine arm	Adjuvant chemotherapy	After surgical resection, patients who are circulating tumor DNA (ctDNA) positive will receive adjuvant chemotherapy for 12-24 weeks during which they will undergo neoantigen prediction, randomization, and vaccine manufacturing. After study treatment screening, patients who are still ctDNA positive with no evidence of residual or metastatic disease will receive a total of 6 doses of GRT-C901/ GRT-R902, 2 doses of ipilimumab, and 13 doses of atezolizumab. Study visits occur every 28 days.
Observation arm	Adjuvant chemotherapy	After surgical resection, patients who are ctDNA positive will receive adjuvant chemotherapy for 12-24 weeks during which they will undergo neoantigen prediction and randomization. After study treatment screening, patients who are still ctDNA positive with no evidence of residual or metastatic disease will be observed via study visits occur every 12 weeks.

Primary Outcome Measures

Name	Time	Method
Incidence and Severity of Adverse Events	Up to ~100 days after last study treatment (Up to 62 weeks)	The incidence and severity will be assessed for treatment-emergent adverse events (TEAEs), immune-related AEs (irAEs), treatment-related AEs, serious AEs (SAEs), AEs leading to death while patients are on treatment or up to 100 days after the last study treatment, AEs leading to dose delays or dose discontinuation, and AEs leading to discontinuation of study treatment using National Cancer Institute (NCI) Criteria for Adverse Events (CTCAE) v5.0
Percentage of Patients with a ≥50% Decrease from Baseline in Circulating Tumor deoxyribonucleic acid (ctDNA)	Baseline and up to ~24 months

Secondary Outcome Measures

Name	Time	Method
Recurrence-free survival (RFS) per Investigator	From time of randomization until first recurrence of the same cancer, or death (Up to ~36 months)
Longest Duration of Molecular response of ctDNA Decrease from Baseline	Baseline and up to ~24 months
Success of Vaccine Manufacture	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.
Overall Survival (OS)	From time of randomization until death due to any cause (Up to ~36 months)
Disease-free survival (DFS) per Investigator	From time of randomization until first recurrence of any cancer, or death (Up to ~36 months)
Conversion of Patients with ctDNA at Baseline to Undetectable ctDNA as Assessed via a Polymerase Chain Reaction (PCR)-Based Assay	Baseline and up to ~24 months
T-cell response using Peripheral Blood Mononuclear Cells (PBMCs)	Up to ~24 months

Trial Locations

Locations (3)

Barbara Ann Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Christ Hospital Cancer Center; 🇺🇸 Cincinnati, Ohio, United States

NYU Langone Health; 🇺🇸 New York, New York, United States