SNPMiner Trials (Home Page)
Report for Mutation G13D
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 5 clinical trials
Clinical Trials
1 Phase II Clinical Study of Cetuximab in Refractory Colorectal Cancer With K-RAS Mutated and Favourable FcγR IIa (CD32) Genotype
This national, multicenter, open-label phase 2 study without any control arm aims to evaluate the activity of cetuximab monotherapy in the treatment of refractory colorectal cancer in subjects with K-RAS mutated and FcγRIIa polymorphism tumors, in which there is no therapeutic alternative for treatment. Failure of the first and second line conventional therapeutic lines was documented.
NCT01450319 Colorectal Neoplasms Drug: Cetuximab MeSH:Colorectal Neoplasms
HPO:Neoplasm of the large intestine
All subjects were analyzed and classified as carriers of every different polymorphism of FCy Receptors: for FCyRIIa (H/H, homozygous alleles with histidine and R/H, heterozygous alleles with arginine/histidine) and FCyRIIIa (V/V, homozygous alleles with valine, F/F, homozygous alleles with phenylalanine and F/V, heterozygous alleles with valine ⁄ phenylalanine) (units: subjects with every type of polymorphism) .The FCyR genotype was determined using a TaqMan Allelic Discrimination Assay.. Overall Survival (OS) Related to Codon G13D. --- G13D ---
Primary Outcomes
Description: Overall survival was defined as the time from date of informed consent signature until death.
Measure: Overall Survival (OS) Time Time: From the date of informed consent signature until death, assessed up to 3 yearsSecondary Outcomes
Description: DCR was defined as those subjects achieving complete response (CR), partial response (PR) or stable disease (SD), according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v.1.1). For target lesions (TLs), CR was defined as the disappearance of all TLs; PR was defined as at least a 30 percent (%) decrease in the sum of longest diameter (SLD) of the TLs, taking as a reference the baseline (BL) SLD; Stable disease (SD) was defined as neither sufficient decrease in SLD to qualify for PR nor sufficient increase in SLD to qualify for PD; and PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since the treatment started. For non-target lesions (NTLs), CR was defined as the disappearance of all NTLs and normalization of tumor marker levels; SD was defined as the persistence of 1 or more NTLs and/or maintenance of tumor marker levels above normal limits; and progressive disease (PD) was defined as the appearance
Measure: Percentage of Subjects With Disease Control Rate (DCR) Time: From the date of informed consent signature until progressive disease, assessed up to 3 yearsDescription: PFS was defined as the time from informed consent signature until PD or death, whatever occurred first. Subjects who did not have disease progression or were lost to follow-up, were censored at the date of last contact, known to be alive and progression free; moreover, those subjects who started a new treatment (different from cetuximab), were censored at the date of starting the new treatment. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from BL or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without second-line PD or death were censored at the date of last tumor assessment where non-progression was documented.
Measure: Progression Free Survival (PFS) Time Time: From the date of informed consent signature until progressive disease (PD) or death, assessed up to 3 yearsDescription: An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Measure: Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, AEs Leading to Death Time: From the date of enrollment up to 30 days after the last dose of study drug administration, assessed up to 3 yearsDescription: The antibody fragment C portion (FCy) of cetuximab interacts with Fc-gamma receptors (FCyRs) expressed by immune effector cells. Polymorphisms were described in genes coding for FCyRIIa and in FCyRIIIa. A histidine/arginine polymorphism at position 131 for FCyRIIa gene and valine ⁄ phenylalanine polymorphism at position 158 for the FCyRIIIa gene were reported to be functionally relevant in the ADCC mechanism. All subjects were analyzed and classified as carriers of every different polymorphism of FCy Receptors: for FCyRIIa (H/H, homozygous alleles with histidine and R/H, heterozygous alleles with arginine/histidine) and FCyRIIIa (V/V, homozygous alleles with valine, F/F, homozygous alleles with phenylalanine and F/V, heterozygous alleles with valine ⁄ phenylalanine) (units: subjects with every type of polymorphism) .The FCyR genotype was determined using a TaqMan Allelic Discrimination Assay.
Measure: Number of Subjects With Fcγ Receptors (FCγR) IIa/IIIa Polymorphisms Time: BaselineDescription: OS was defined as the time from informed consent signature until death. Subjects without death were censored at the last date known alive (within the study).
Measure: Overall Survival (OS) Related to Codon G13D Time: From the date of informed consent signature until death, lost-to-follow-up or end of study, whatever occurred first (maximal up to 3 years)Description: OS was defined as the time from informed consent signature until death. Subjects without death were censored at the last date known alive (within the study).
Measure: Overall Survival (OS) Related to Killer Inhibitory Receptors 2DS4 (KIR2DS4) Functional Receptor (f/d) and Non-functional Receptor (NFR) Time: From the date of informed consent signature until death, lost-to-follow-up or end of study, whatever occurred first (maximal assessed up to 3 years)Measure: Beta 2-microglobulin Time: Baseline, Week 8
2 Comparison of KRAS/BRAF Mutational Status Between Tumor Tissue Section Analysis With Conventional Techniques and Plasma Samples Analysis (KPLEX2)
The goal of this multicenter prospective study is to validate, and ultimately translate in routine clinical practice, the use of plasma analysis of ccfDNA for the determination of KRAS mutation status in mCRC patients.
NCT02784639 Colorectal Cancer Other: Plasma Analysis of circulating cell free DNA Other: Tumor tissue analysis of circulating cell free DNA MeSH:Colorectal Neoplasms
HPO:Neoplasm of the large intestine
As a consequence, the method was adapted to detect the six more frequent KRAS mutations in CRC (G12D, G12V, G13D, G12S, G12C, G12A) and the BRAF V600E. --- G12D --- --- G12V --- --- G13D ---
Primary Outcomes
Description: Area under the ROC curve of the mutation percentage obtained from plasma ccfDNA analysis
Measure: Area under ROC curve Time: 12 month3 A Phase Ib, Open-label, Multicenter, Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Cobimetinib and HM95573 in Patients With Locally Advanced or Metastatic Solid Tumors
This study evaluates the safety, tolerability and pharmacokinetics of cobimetinib and HM95573 in patient with locally advanced or metastatic solid tumors.
NCT03284502 Locally Advanced Solid Tumor Metastatic Solid Tumor Drug: HM95573, cobimetinib Drug: HM95573, cobimetinib MeSH:Neoplasms
HPO:Neoplasm
No prior treatment with regorafenib in the CRC (KRAS G13D- and BRAF V600- mutant) expansion cohort II. --- G13D ---
2. Expansion cohort II (HM95573 300 mg BID + cobimetinib 20 mg QOD (3 times a week: day 1, 3, 5, 8, 10, 12, 15, 17, 19 of 28 day cycle)): - KRAS G13D- mutant CRC - BRAF V600- mutant CRC - NRAS-mutant Melanoma - RAS- or RAF-mutant solid tumors (basket cohort: A minimum of 10 BRAF V600 melanoma will be enrolled) - BRAF Class II-mutant (including BRAF fusions) or Class III-mutant solid tumors 15. --- G13D ---
Primary Outcomes
Measure: Percentage of patients with Adverse Events, Serious Adverse Events and Adverse Events of Special Interest as assessed by CTCAE v4.0 Time: up to approximately 3 yearsMeasure: Number of patients with DLT of cobimetinib and HM95573 Time: 28 days
Measure: Number of patients with MTD of cobimetinib and HM95573 Time: End of Stage 1, an approximately 2 years
Measure: Recommended Phase II dose (RPIID) of cobimetinib and HM95573 Time: End of Stage 1, an approximately 2 years
Secondary Outcomes
Measure: Area Under the Concentration-Time Curve (AUC) of cobimetinib and HM95573 Time: Cycle1 Day1, Cycle1 Day15, Cycle1 Day21, Cycle2 Day1, Cycle3 Day1, Study completion, an approximately 2 yearsMeasure: Maximum Serum Concentration (Cmax) of cobimetinib and HM95573 Time: Cycle1 Day1, Cycle1 Day15, Cycle1 Day21, Cycle2 Day1, Cycle3 Day1, Study completion, an approximately 2 years
Measure: Time to maximum concentration (Tmax) of cobimetinib and HM95573 Time: Cycle1 Day1, Cycle1 Day15, Cycle1 Day21, Cycle2 Day1, Cycle3 Day1, Study completion, an approximately 2 years
Measure: FDG-PET and molecular biomarkers assessed in pre and post treatment tumor tissues Time: Screening, Cycle1 Day15
Measure: Preliminary assessment of the anti tumor activity of cobimetinib and HM95573 combination measured by RECIST v1.1. Time: Screening, During Days 22-28 (Day 25 ± 3 days) in Cycle 2 and 4, and then every 8 weeks (±7 days), until disease progression, assessed approximately 3 years
4 A Phase 1, Open-Label, Multicenter Study to Assess the Safety and Tolerability of mRNA-5671/V941 as a Monotherapy and in Combination With Pembrolizumab in Participants With KRAS Mutant Advanced or Metastatic Non-Small Cell Lung Cancer, Colorectal Cancer or Pancreatic Adenocarcinoma
This study will determine the safety and tolerability and establish a preliminary recommended Phase 2 dose of V941(mRNA-5671/V941) as a monotherapy and in combination with pembrolizumab infusion.
NCT03948763 Neoplasms Carcinoma, Non-Small-Cell Lung Pancreatic Neoplasms Colorectal Neoplasms Biological: V941 Biological: Pembrolizumab MeSH:Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms Pancreatic Neoplasms Neoplasms
HPO:Neoplasm Neoplasm of the large intestine Neoplasm of the pancreas Non-small cell lung carcinoma
All - Has a histologically confirmed advanced or metastatic KRAS 4MUT+ (G12D, G12V, G13D or G12C) (4 prevalent KRAS mutant antigens in solid tumors) solid tumor identified by local laboratory testing, and who have received, or been intolerant to, or ineligible for all treatment known to confer clinical benefit. --- G12D --- --- G12V --- --- G13D ---
Primary Outcomes
Description: The following toxicities graded for severity using NCI Common Terminology for Adverse Events (CTCAE), Version 4.0 will be considered a DLT if judged by the investigator to be possibly related to study investigational products: 1) Grade 4 nonhematologic toxicity (ie. not a laboratory finding). 2) Grade 4 hematologic toxicity lasting ≥ 7 days, except thrombocytopenia: 3) Grade 4 thrombocytopenia of any duration 4) Grade 3 thrombocytopenia associated with clinically significant bleeding 5) Any nonhematologic AE ≥ Grade 3 in severity, with some exceptions 6) Any Grade 3 or Grade 4 nonhematologic laboratory value that meets one of the study criteria 7) Febrile neutropenia Grade 3 or Grade 4 8) Prolonged delay (> 2 weeks) in initiating Cycle 2 due to treatment-related toxicity. 9) Any treatment-related toxicity that causes the participant to discontinue treatment during Cycle 1. 10) Grade 5 toxicity 11) Any other clinically significant toxicity judged to be a DLT by the investigator.
Measure: Dose-Limiting Toxicities (DLTs) Time: Cycle 1 (Up to 21 days)Description: Number of participants who experienced an AE. An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Measure: Adverse Events (AEs) Time: Up to approximately 25 monthsDescription: Number of participants who discontinued from study due to an AE. An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Measure: Discontinuations Time: Up to approximately 24 monthsSecondary Outcomes
Description: ORR is assessed by the investigator based on Response Rate Assessed by Modified Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) and RECIST for immune-based therapeutics (iRECIST) following administration of V941 in combination with pembrolizumab. Objective response is a confirmed complete response (CR) or partial response (PR).
Measure: Objective Response Rate (ORR) Time: Up to approximately 24 monthsDescription: Presence of and changes in the quantity of mutant KRAS specific T cells in the blood.
Measure: Mutant KRAS Specific T cells Time: Up to approximately 24 monthsOther Outcomes
Description: T-cell receptor (TCR) clonality and diversity in the periphery and tumor.
Measure: T-cell receptor (TCR) Time: Up to approximately 24 months5 First-in-Human, Phase 1/1b, Open-label, Multicenter Study of Bifunctional EGFR/TGFβ Fusion Protein BCA101 Alone and in Combination With Pembrolizumab in Patients With EGFR-Driven Advanced Solid Tumors
The investigational drug to be studied in this protocol, BCA101, is a first-in-class compound that targets both EGFR with TGFβ. Based on preclinical data, this bifunctional antibody may exert synergistic activity in patients with EGFR-driven tumors.
NCT04429542 TNBC - Triple-Negative Breast Cancer Head and Neck Squamous Cell Carcinoma Squamous Cell Carcinoma of Anal Canal Uveal Melanoma Glioblastoma Colorectal Cancer Chordoma Squamous Cell Carcinoma of the Lung KRAS G12D KRAS G13D EGFR Amplification Epithelial Ovarian Cancer Hepatocellular Carcinoma Anaplastic Thyroid Cancer Pancreas Cancer Drug: BCA101 Drug: Pembrolizumab MeSH:Carcinoma Carcinoma, Squamous Cell Glioblastoma Triple Negative Breast Neoplasms Squamous Cell Carcinoma of Head and Neck Carcinoma, Ovarian Epithelial Pancreatic Neoplasms Chordoma Thyroid Carcinoma, Anaplastic Lung Neoplasms
HPO:Anaplastic thyroid carcinoma Carcinoma Chordoma Glioblastoma multiforme Neoplasm of the lung Neoplasm of the pancreas Squamous cell carcinoma
i Single agent BCA101 - patients with the following tumor types will be eligible: 1) Squamous Cell Lung Cancer (SqCLC) 2) Squamous Cell Carcinoma of the Head and Neck (HNSCC) 3) RAS wild-type microsatellite stable Colorectal Carcinoma (RAS WT MSS CRC) 4) Triple Negative Breast Cancer (TNBC) 5) Chordoma 6) Squamous Cell Carcinoma of the Anal Canal (SCCAC) 7) Uveal Melanoma 8) Glioblastoma (GBM) 9) Gastric Cancer 10) Any solid tumor with a KRAS G12D or G13D mutation 11) Any solid tumor with EGFR amplification 12) Epithelial Ovarian Cancer 13) Hepatocellular Carcinoma (HCC) 14) Anaplastic Thyroid Cancer (ATC) 15) Pancreatic Cancer 16) Other EGFR-driven advanced solid tumors (if there is compelling data or evidence to enroll a patient with a tumor type other than those listed in 1 - 15, the treating physician may discuss the patient with the Sponsor to determine eligibility). --- G12D --- --- G13D ---
i Single agent BCA101 - patients with the following tumor types will be eligible: 1. PD-L1 negative, EGFR-amplified SqCLC 2. RAS WT MSS CRC 3. EGFR-amplified TNBC 4. Any solid tumor with a KRAS G12D or G13D mutation ii. --- G12D --- --- G13D ---
TNBC - Triple-Negative Breast Cancer Head and Neck Squamous Cell Carcinoma Squamous Cell Carcinoma of Anal Canal Uveal Melanoma Glioblastoma Colorectal Cancer Chordoma Squamous Cell Carcinoma of the Lung KRAS G12D KRAS G13D EGFR Amplification Epithelial Ovarian Cancer Hepatocellular Carcinoma Anaplastic Thyroid Cancer Pancreas Cancer Carcinoma Carcinoma, Squamous Cell Glioblastoma Triple Negative Breast Neoplasms Squamous Cell Carcinoma of Head and Neck Carcinoma, Ovarian Epithelial Pancreatic Neoplasms Chordoma Thyroid Carcinoma, Anaplastic Lung Neoplasms This is a Phase 1/1b, open-label study, which consists of dose escalation parts (Part A) followed by expansion cohorts (Part B) for both single agent BCA101 and combination BCA101 plus pembrolizumab. --- G12D --- --- G13D ---
Planned expansion cohorts for single agent BCA101 include 1) PD-L1 negative, EGFR-amplified Squamous Cell Lung Cancer (SqCLC); 2) RAS wild-type, microsatellite stable Colorectal Carcinoma (RAS wt, MSS CRC); 3) EGFR-amplified Triple Negative Breast Cancer; and 4) any solid tumor with either a KRAS G12D or G13D mutation. --- G12D --- --- G13D ---
Primary Outcomes
Description: Incidence and severity of AEs and SAEs
Measure: Safety of BCA101 alone and BCA101 in combination with pembrolizumab: Incidence and severity of AEs and SAEs Time: 24 monthsDescription: Incidence and severity of AEs and SAEs
Measure: Tolerability of BCA101 alone and BCA101 in combination with pembrolizumab: Incidence and severity of AEs and SAEs Time: 24 monthsDescription: Incidence of DLTs during the first cycle of treatment with BCA101 monotherapy or the combination of BCA101 and pembrolizumab.
Measure: Incidence of Dose Limiting Toxicities (DLTs) Time: 21 daysSecondary Outcomes
Description: Determine objective response rate in each part of the study, per RECIST v1.1 and iRECIST
Measure: Objective Response Rate Time: 24 monthsDescription: Determine clinical benefit rate in each part of the study, per RECIST v1.1 and iRECIST
Measure: Clinical Benefit Rate Time: 24 monthsDescription: Determine PFS in each part of the study, per RECIST v1.1 and iRECIST
Measure: Progression free survival Time: 24 monthsDescription: Determine duration of response in each part of the study, per RECIST v1.1 and iRECIST
Measure: Duration of Response Time: 24 monthsDescription: Determine survival rates in each part of the study.
Measure: Overall Survival Time: 24 monthsDescription: AUC
Measure: AUC of BCA101 and pembrolizumab Time: 24 monthsDescription: Cmax
Measure: Cmax of BCA101 and pembrolizumab Time: 24 monthsDescription: Tmax
Measure: Tmax of BCA101 and pembrolizumab Time: 24 monthsDescription: Ctrough
Measure: Concentration vs time profile of BCA101 and pembrolizumab Time: 24 monthsDescription: Half-life
Measure: Half-life of BCA101 and pembrolizumab Time: 24 monthsDescription: Incidence and titer of anti-drug-antibodies
Measure: Immunogenicity of BCA101 and pembrolizumab Time: 24 months