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DRUG:

KRAS peptide vaccine

i
Other names: KRAS peptide vaccine, SLP mKRASvax
Associations
Company:
Sidney Kimmel Comprehensive Cancer Center
Drug class:
Immunostimulant, KRAS inhibitor
Related drugs:
Associations
9ms
Pooled Mutant KRAS-Targeted Long Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Resected Mismatch Repair Protein (MMR-p) Colorectal and Pancreatic Cancer (clinicaltrials.gov)
P1, N=30, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2024 --> Aug 2025 | Trial primary completion date: Dec 2024 --> Aug 2025
Trial completion date • Trial primary completion date • Mismatch repair
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KRAS (KRAS proto-oncogene GTPase) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
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KRAS mutation
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Opdivo (nivolumab) • Yervoy (ipilimumab) • Hiltonol (poly-ICLC) • KRAS peptide vaccine
1year
Barcoding intracellular reverse transcription enables high-throughput phenotype-coupled T cell receptor analyses. (PubMed, Cell Rep Methods)
We used INCERTS to discover antigen-specific TCRs from patients with cancer immunized with a novel mutant KRAS peptide vaccine. After ex vivo stimulation, 28 uniquely barcoded samples were pooled prior to FACS into peptide-reactive and non-reactive CD4 and CD8 populations. Combining complementary patient-matched single-cell RNA sequencing (scRNA-seq) data enabled retrieval of full-length, paired TCR alpha and beta chain sequences for future validation of therapeutic utility.
Journal • IO biomarker
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KRAS (KRAS proto-oncogene GTPase) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
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KRAS mutation
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KRAS peptide vaccine
over1year
Pooled Mutant KRAS-Targeted Long Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Resected MMR-p Colorectal and Pancreatic Cancer (clinicaltrials.gov)
P1, N=30, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jun 2024 --> Dec 2024 | Trial primary completion date: Jun 2024 --> Dec 2024
Trial completion date • Trial primary completion date
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KRAS (KRAS proto-oncogene GTPase) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
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KRAS mutation
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Opdivo (nivolumab) • Yervoy (ipilimumab) • Hiltonol (poly-ICLC) • KRAS peptide vaccine
over1year
A pooled mutant KRAS peptide vaccine activates polyfunctional T cell responses in patients with resected pancreatic cancer (AACR 2023)
Patients with no evidence of disease on imaging within 6 months of completion of adjuvant chemotherapy were vaccinated with the mKRAS vaccine (0.3mg/peptide and 0.5mg poly-ICLC (Hiltonol: Oncovir)) weekly for 4 doses followed by booster vaccines every 8 weeks. Patients also received ipilimumab (1mg/kg, every 6 weeks for 2 doses) and nivolumab (3mg/kg, every 3 weeks in the priming phase) followed by nivolumab (480mg, flat dose in boost phase)... This study thus far indicates the induction of de novo, high quality mKRAS-specific T cells in the periphery post-vaccine. Ongoing studies will define TCR diversity and clonality of mKRAS-specific T cells to each mKRAS epitope. Overall, our data will be used to identify peripheral T cell-based biomarkers that may be able to predict response to mKRAS-targeted immunotherapy.
Clinical • Late-breaking abstract • PD(L)-1 Biomarker • IO biomarker
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KRAS (KRAS proto-oncogene GTPase) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • CD4 (CD4 Molecule) • IL2 (Interleukin 2)
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KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • KRAS G12A • KRAS G12 • KRAS G13
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Opdivo (nivolumab) • Yervoy (ipilimumab) • Hiltonol (poly-ICLC) • KRAS peptide vaccine
over2years
Pooled Mutant KRAS-Targeted Peptide Vaccine with Nivolumab and Ipilimumab in Advanced KRAS Mutated Non-Small Cell Lung Cancer (IASLC-WCLC 2022)
Through preclinical and early (ongoing) clinical trial data, our institution has shown the benefits of combining targeted synthetic long peptide vaccines with ICB and adjuvant stimulants in treatment of solid malignancies. This is a single institution, phase I study for patients with Stage III/IV unresectable KRAS-mutated NSCLC to evaluate safety of the pooled mutant-KRAS peptide vaccine with poly-ICLC adjuvant in combination with nivolumab and ipilimumab in the first line treatment setting. The secondary objectives are to assess the impact of therapy on mutant-KRAS specific T cell responses in the peripheral blood and estimate the progression free survival (PFS) for patients treated with this combination. Correlative studies will assess the impact of predicted KRAS mutations on mutant-KRAS specific T cell responses in the peripheral blood, as well as evaluate dynamic genomic alterations of response and resistance through ctDNA analysis.
PD(L)-1 Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1)
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KRAS mutation • EGFR mutation • KRAS G12C • KRAS G12D • KRAS G12V • STK11 mutation • KRAS G13D • ALK mutation • KRAS G12R • KEAP1 mutation • KRAS G12A • KRAS G12
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Opdivo (nivolumab) • Yervoy (ipilimumab) • Hiltonol (poly-ICLC) • KRAS peptide vaccine
over2years
Mutant KRAS -Targeted Long Peptide Vaccine for Patients at High Risk of Developing Pancreatic Cancer (clinicaltrials.gov)
P1, N=25, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting --> Recruiting
Enrollment open
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KRAS (KRAS proto-oncogene GTPase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CD4 (CD4 Molecule) • EPCAM (Epithelial cell adhesion molecule) • PMS1 (PMS1 protein homolog 1)
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KRAS mutation • PALB2 mutation • CDKN2A mutation • MLH1 mutation • PMS1 mutation
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Hiltonol (poly-ICLC) • KRAS peptide vaccine
almost3years
Mutant Kirsten Rat Sarcoma (KRAS) -Targeted Long Peptide Vaccine for Patients at High Risk of Developing Pancreatic Cancer (clinicaltrials.gov)
P1, N=25, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2025 --> Mar 2026 | Initiation date: Dec 2021 --> Mar 2022 | Trial primary completion date: Dec 2025 --> Mar 2026
Preclinical • Trial completion date • Trial initiation date • Trial primary completion date
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KRAS (KRAS proto-oncogene GTPase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CD4 (CD4 Molecule) • EPCAM (Epithelial cell adhesion molecule) • PMS1 (PMS1 protein homolog 1)
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KRAS mutation • PALB2 mutation • CDKN2A mutation • PMS1 mutation
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Hiltonol (poly-ICLC) • KRAS peptide vaccine
over3years
Clinical • New P1 trial • Preclinical
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KRAS (KRAS proto-oncogene GTPase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CD4 (CD4 Molecule) • EPCAM (Epithelial cell adhesion molecule) • PMS1 (PMS1 protein homolog 1)
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KRAS mutation • PALB2 mutation • CDKN2A mutation • PMS1 mutation
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Hiltonol (poly-ICLC) • KRAS peptide vaccine
over3years
Inhibition of lung tumorigenesis by a small molecule CA170 targeting the immune checkpoint protein VISTA. (PubMed, Commun Biol)
Remarkably, lung tumor development was almost completely suppressed when CA170 was combined with an MHCII-directed KRAS peptide vaccine. Flow cytometry and single-cell RNA sequencing (scRNA-seq) revealed that CA170 increased CD8 T cell infiltration and enhanced their effector functions by decreasing the tumor infiltration of myeloid-derived suppressor cells (MDSCs) and Regulatory T (Treg) cells, while the Kras vaccine primarily induced expansion of CD4 effector T cells. VISTA antagonism by CA170 revealed strong efficacy against lung tumorigenesis with broad immunoregulatory functions that influence effector, memory and regulatory T cells, and drives an adaptive T cell tumor-specific immune response that enhances the efficacy of the KRAS vaccine.
Journal
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KRAS (KRAS proto-oncogene GTPase) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
|
KRAS peptide vaccine
over4years
Pooled Mutant KRAS-Targeted Long Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Resected MMR-p Colorectal and Pancreatic Cancer (clinicaltrials.gov)
P1, N=30, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting --> Recruiting
Clinical • Enrollment open • PD(L)-1 Biomarker
|
KRAS (KRAS proto-oncogene GTPase) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • CD4 (CD4 Molecule)
|
KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • KRAS G13D • KRAS G12R • KRAS G12A • KRAS G12
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Opdivo (nivolumab) • Yervoy (ipilimumab) • Hiltonol (poly-ICLC) • KRAS peptide vaccine
over4years
Potentiation of Kras peptide cancer vaccine by avasimibe, a cholesterol modulator. (PubMed, EBioMedicine)
Avasimibe complements the efficacy of a multi-peptide Kras vaccine in controlling lung cancer development and growth. This treatment regimen represents a novel immunoprevention approach to prevent lung cancer.
Journal
|
KRAS (KRAS proto-oncogene GTPase) • CD8 (cluster of differentiation 8)
|
KRAS mutation
|
KRAS peptide vaccine
over4years
Pooled Mutant KRAS-Targeted Long Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Resected MMR-p Colorectal and Pancreatic Cancer (clinicaltrials.gov)
P1, N=30, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2024 --> Apr 2024 | Trial primary completion date: Dec 2024 --> Apr 2024
Clinical • Trial completion date • Trial primary completion date • PD(L)-1 Biomarker
|
KRAS (KRAS proto-oncogene GTPase) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • CD4 (CD4 Molecule)
|
KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • KRAS G13D • KRAS G12R • KRAS G12A • KRAS G12
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • Hiltonol (poly-ICLC) • KRAS peptide vaccine
almost5years
Pooled Mutant KRAS-Targeted Long Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Resected MMR-p Colorectal and Pancreatic Cancer (clinicaltrials.gov)
P1, N=30, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
Clinical • Trial completion date • Trial primary completion date • PD(L)-1 Biomarker
|
KRAS (KRAS proto-oncogene GTPase) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • CD4 (CD4 Molecule)
|
KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • KRAS G13D • KRAS G12R • KRAS G12A • KRAS G12
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • Hiltonol (poly-ICLC) • KRAS peptide vaccine