This Phase 3 study will evaluate the efficacy of the investigational agent MRTX849 versus docetaxel in patients who have been previously treated for metastatic NSCLC with a KRAS G12C mutation.

NCT04685135

Conditions

1. Metastatic Non Small Cell Lung Cancer
2. Advanced Non Small Cell Lung Cancer

Interventions

1. Drug: MRTX849
2. Drug: Docetaxel

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

A Randomized Phase 3 Study of MRTX849 Versus Docetaxel in Patients With Previously Treated Non-Small Cell Lung Cancer With KRAS G12C Mutation. --- G12C ---

Phase 3 Study of MRTX849 vs Docetaxel in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation This Phase 3 study will evaluate the efficacy of the investigational agent MRTX849 versus docetaxel in patients who have been previously treated for metastatic NSCLC with a KRAS G12C mutation. --- G12C ---

Phase 3 Study of MRTX849 vs Docetaxel in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation This Phase 3 study will evaluate the efficacy of the investigational agent MRTX849 versus docetaxel in patients who have been previously treated for metastatic NSCLC with a KRAS G12C mutation. --- G12C --- --- G12C ---

To be assessed by European Quality of Life Five Dimensions Questionnaire (EQ-5D-5L).. Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of NSCLC with KRAS G12C mutation. --- G12C ---

Exclusion Criteria: - Prior treatment with an agent targeting KRAS G12C (e.g., AMG 510). --- G12C ---

Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of NSCLC with KRAS G12C mutation. --- G12C ---

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

Conditions

1. Colorectal Cancer

Interventions

1. Other: Plasma Analysis of circulating cell free DNA
2. 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 --- --- G12S --- --- G12C ---

The purpose of this study is to determine if it is safe to add multiple immunotherapies to standard chemotherapy and radiation for treating pancreatic cancer tumors that cannot be completely removed by surgery. 1. GI-4000 Vaccination: The first involves a "vaccine," which is an injection (shot) that teaches your immune system to attack foreign invaders. The vaccine we will use is called "GI-4000" - a vaccine composed of yeast that is made to carry the same proteins (called "mutated Ras proteins") found in some pancreatic cancer cells. 2. Adoptive T-cell Transfer: The second type of immunotherapy in this study is called "adoptive T-cell transfer." This involves collecting a specific type of white blood cells from you (called "T-cells")and growing T-cells grown in a lab which may help the research participants' immune systems recover more quickly after chemotherapy, and possibly improved response to other immunotherapies. We hope that studying these agents together will teach us how to help the immune system fight pancreatic cancer.

NCT00837135

Conditions

1. Pancreatic Cancer

Interventions

1. Other: Screening
2. Biological: GI-4000 Vaccine
3. Biological: GI-4000 Vaccine + Activated T Cells
4. Biological: Surgical Evaluation after Vaccine #4

MeSH:Pancreatic Neoplasms

HPO:Neoplasm of the pancreas

1. Histologically-confirmed pancreatic adenocarcinoma that expresses one of the GI-4000-related k-ras oncoproteins (G12V, G12C, G12D, Q61L, or Q61R) 2. Locally advanced disease, (stages I-III, i.e no evidence of metastasis outside the pancreas and its regional lymph nodes). --- G12V --- --- G12C ---

This is a Phase I dose-escalation and dose-expansion study that will evaluate the safety, pharmacokinetics (PK), and preliminary activity of GDC-6036 in patients with advanced or metastatic solid tumors with a KRAS G12C mutation.

NCT04449874

Conditions

1. Non-Small Cell Lung Cancer
2. Colorectal Cancer
3. Advanced Solid Tumors

Interventions

1. Drug: GDC-6036

MeSH:Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms

HPO:Neoplasm of the large intestine Non-small cell lung carcinoma

A Phase I Dose-Escalation and Dose-Expansion Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-6036 in Patients With Advanced or Metastatic Solid Tumors With a KRAS G12C Mutation. --- G12C ---

A Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-6036 in Participants With Advanced or Metastatic Solid Tumors With a KRAS G12C Mutation This is a Phase I dose-escalation and dose-expansion study that will evaluate the safety, pharmacokinetics (PK), and preliminary activity of GDC-6036 in patients with advanced or metastatic solid tumors with a KRAS G12C mutation. --- G12C ---

A Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-6036 in Participants With Advanced or Metastatic Solid Tumors With a KRAS G12C Mutation This is a Phase I dose-escalation and dose-expansion study that will evaluate the safety, pharmacokinetics (PK), and preliminary activity of GDC-6036 in patients with advanced or metastatic solid tumors with a KRAS G12C mutation. --- G12C --- --- G12C ---

Inclusion Criteria: - Histologically documented advanced or metastatic solid tumor with KRAS G12C mutation. --- G12C ---

This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 in patients with advanced solid tumors that have a KRAS G12C mutation.

NCT03785249

Conditions

1. Advanced Cancer
2. Metastatic Cancer
3. Malignant Neoplastic Disease

Interventions

1. Drug: MRTX849
2. Drug: Pembrolizumab
3. Drug: Cetuximab
4. Drug: Afatinib

MeSH:Neoplasm Metastasis Neoplasms

HPO:Neoplasm

A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1. --- G12C ---

Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1 This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 in patients with advanced solid tumors that have a KRAS G12C mutation. --- G12C ---

Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1 This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 in patients with advanced solid tumors that have a KRAS G12C mutation. --- G12C --- --- G12C ---

Characterize the safety of MRTX849 in patients having advanced solid tumor malignancies with KRAS G12C mutation. --- G12C ---

Inclusion Criteria: - Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation - Unresectable or metastatic disease - Standard treatment is not available or patient declines - Adequate organ function Exclusion Criteria: - History of intestinal disease or major gastric surgery or inability to swallow oral medications - Other active cancer Inclusion Criteria: - Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation - Unresectable or metastatic disease - Standard treatment is not available or patient declines - Adequate organ function Exclusion Criteria: - History of intestinal disease or major gastric surgery or inability to swallow oral medications - Other active cancer Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease Neoplasm Metastasis Neoplasms This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 in patients with advanced solid tumors with a KRAS G12C mutation. --- G12C ---

Inclusion Criteria: - Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation - Unresectable or metastatic disease - Standard treatment is not available or patient declines - Adequate organ function Exclusion Criteria: - History of intestinal disease or major gastric surgery or inability to swallow oral medications - Other active cancer Inclusion Criteria: - Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation - Unresectable or metastatic disease - Standard treatment is not available or patient declines - Adequate organ function Exclusion Criteria: - History of intestinal disease or major gastric surgery or inability to swallow oral medications - Other active cancer Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease Neoplasm Metastasis Neoplasms This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 in patients with advanced solid tumors with a KRAS G12C mutation. --- G12C --- --- G12C ---

Inclusion Criteria: - Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation - Unresectable or metastatic disease - Standard treatment is not available or patient declines - Adequate organ function Exclusion Criteria: - History of intestinal disease or major gastric surgery or inability to swallow oral medications - Other active cancer Inclusion Criteria: - Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation - Unresectable or metastatic disease - Standard treatment is not available or patient declines - Adequate organ function Exclusion Criteria: - History of intestinal disease or major gastric surgery or inability to swallow oral medications - Other active cancer Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease Neoplasm Metastasis Neoplasms This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 in patients with advanced solid tumors with a KRAS G12C mutation. --- G12C --- --- G12C --- --- G12C ---

MRTX849 is an orally-available small molecule inhibitor of KRAS G12C. --- G12C ---

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

Conditions

1. Neoplasms
2. Carcinoma, Non-Small-Cell Lung
3. Pancreatic Neoplasms
4. Colorectal Neoplasms

Interventions

1. Biological: V941
2. Biological: Pembrolizumab

MeSH:Neoplasms Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms Pancreatic 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 --- --- G12C ---

This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors that have a KRAS G12C mutation.

NCT04330664

Conditions

1. Advanced Cancer
2. Metastatic Cancer
3. Malignant Neoplastic Disease

Interventions

1. Drug: MRTX849
2. Drug: TNO155

MeSH:Neoplasm Metastasis Neoplasms

HPO:Neoplasm

A Phase 1/2 Trial of MRTX849 in Combination With TNO155 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL 2. Phase 1/2 Study in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL 2 This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors that have a KRAS G12C mutation. --- G12C ---

A Phase 1/2 Trial of MRTX849 in Combination With TNO155 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL 2. Phase 1/2 Study in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL 2 This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors that have a KRAS G12C mutation. --- G12C --- --- G12C ---

A Phase 1/2 Trial of MRTX849 in Combination With TNO155 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL 2. Phase 1/2 Study in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL 2 This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors that have a KRAS G12C mutation. --- G12C --- --- G12C --- --- G12C ---

Characterize the safety of MRTX849 and TNO155 in patients having advanced solid tumor malignancies with KRAS G12C mutation.. Number of participants with treatment related adverse events. --- G12C ---

Inclusion Criteria: - Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation (phase 2 must be either Non-Small Cell Lung Cancer or Colorectal Cancer) - Unresectable or metastatic disease - No available treatment with curative intent - Adequate organ function Exclusion Criteria: - History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow - Other active cancer - Cardiac abnormalities Inclusion Criteria: - Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation (phase 2 must be either Non-Small Cell Lung Cancer or Colorectal Cancer) - Unresectable or metastatic disease - No available treatment with curative intent - Adequate organ function Exclusion Criteria: - History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow - Other active cancer - Cardiac abnormalities Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease Neoplasm Metastasis Neoplasms This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors with a KRAS G12C mutation. --- G12C ---

Inclusion Criteria: - Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation (phase 2 must be either Non-Small Cell Lung Cancer or Colorectal Cancer) - Unresectable or metastatic disease - No available treatment with curative intent - Adequate organ function Exclusion Criteria: - History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow - Other active cancer - Cardiac abnormalities Inclusion Criteria: - Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation (phase 2 must be either Non-Small Cell Lung Cancer or Colorectal Cancer) - Unresectable or metastatic disease - No available treatment with curative intent - Adequate organ function Exclusion Criteria: - History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow - Other active cancer - Cardiac abnormalities Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease Neoplasm Metastasis Neoplasms This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors with a KRAS G12C mutation. --- G12C --- --- G12C ---

Inclusion Criteria: - Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation (phase 2 must be either Non-Small Cell Lung Cancer or Colorectal Cancer) - Unresectable or metastatic disease - No available treatment with curative intent - Adequate organ function Exclusion Criteria: - History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow - Other active cancer - Cardiac abnormalities Inclusion Criteria: - Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation (phase 2 must be either Non-Small Cell Lung Cancer or Colorectal Cancer) - Unresectable or metastatic disease - No available treatment with curative intent - Adequate organ function Exclusion Criteria: - History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow - Other active cancer - Cardiac abnormalities Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease Neoplasm Metastasis Neoplasms This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors with a KRAS G12C mutation. --- G12C --- --- G12C --- --- G12C ---

MRTX849 is an orally available small molecule inhibitor of KRAS G12C and TNO155 is a selective, orally bioavailable allosteric inhibitor of wild-type SHP2. --- G12C ---

The reason for this study is to see if the study drug LY3499446 is safe and effective in participants with solid tumors with KRAS G12C mutation.

NCT04165031

Conditions

1. Advanced Solid Tumor
2. Non-Small Cell Lung Cancer
3. Colorecta
4. Colorectal Cancer

Interventions

1. Drug: LY3499446
2. Drug: Abemaciclib
3. Drug: Cetuximab
4. Drug: Erlotinib
5. Drug: Docetaxel

MeSH:Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms

HPO:Neoplasm of the large intestine Non-small cell lung carcinoma

A Phase 1/2 Study of LY3499446 Administered to Patients With Advanced Solid Tumors With KRAS G12C Mutation. --- G12C ---

A Study of LY3499446 in Participants With Advanced Solid Tumors With KRAS G12C Mutation The reason for this study is to see if the study drug LY3499446 is safe and effective in participants with solid tumors with KRAS G12C mutation. --- G12C ---

A Study of LY3499446 in Participants With Advanced Solid Tumors With KRAS G12C Mutation The reason for this study is to see if the study drug LY3499446 is safe and effective in participants with solid tumors with KRAS G12C mutation. --- G12C --- --- G12C ---

Inclusion Criteria: - Participants must have diagnosis of a solid tumor with KRAS G12C mutation that did not respond to at least 1 line of standard therapy and has spread to other part(s) of the body - For phase II, participants must be willing to have new tumor tissue biopsies (doctor removes a small amount of tissue) during the study if it does not cause undue risks to health - Participants must be willing to use highly effective birth control - Participants must have adequate organ function - Participants must be able to swallow capsules Exclusion Criteria: - Participants must not have certain infections such as hepatitis or tuberculosis or HIV that is not well controlled - Participants must not have another serious medical condition including a serious heart condition, such as congestive heart failure, unstable angina pectoris, or heart attack within the last three months - Participants must not have cancer of the central nervous system that is not stable - Participants must not be pregnant or breastfeeding - Participants must not use herbal supplements Inclusion Criteria: - Participants must have diagnosis of a solid tumor with KRAS G12C mutation that did not respond to at least 1 line of standard therapy and has spread to other part(s) of the body - For phase II, participants must be willing to have new tumor tissue biopsies (doctor removes a small amount of tissue) during the study if it does not cause undue risks to health - Participants must be willing to use highly effective birth control - Participants must have adequate organ function - Participants must be able to swallow capsules Exclusion Criteria: - Participants must not have certain infections such as hepatitis or tuberculosis or HIV that is not well controlled - Participants must not have another serious medical condition including a serious heart condition, such as congestive heart failure, unstable angina pectoris, or heart attack within the last three months - Participants must not have cancer of the central nervous system that is not stable - Participants must not be pregnant or breastfeeding - Participants must not use herbal supplements Advanced Solid Tumor Non-Small Cell Lung Cancer Colorecta Colorectal Cancer Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms null --- G12C ---

Inclusion Criteria: - Participants must have diagnosis of a solid tumor with KRAS G12C mutation that did not respond to at least 1 line of standard therapy and has spread to other part(s) of the body - For phase II, participants must be willing to have new tumor tissue biopsies (doctor removes a small amount of tissue) during the study if it does not cause undue risks to health - Participants must be willing to use highly effective birth control - Participants must have adequate organ function - Participants must be able to swallow capsules Exclusion Criteria: - Participants must not have certain infections such as hepatitis or tuberculosis or HIV that is not well controlled - Participants must not have another serious medical condition including a serious heart condition, such as congestive heart failure, unstable angina pectoris, or heart attack within the last three months - Participants must not have cancer of the central nervous system that is not stable - Participants must not be pregnant or breastfeeding - Participants must not use herbal supplements Inclusion Criteria: - Participants must have diagnosis of a solid tumor with KRAS G12C mutation that did not respond to at least 1 line of standard therapy and has spread to other part(s) of the body - For phase II, participants must be willing to have new tumor tissue biopsies (doctor removes a small amount of tissue) during the study if it does not cause undue risks to health - Participants must be willing to use highly effective birth control - Participants must have adequate organ function - Participants must be able to swallow capsules Exclusion Criteria: - Participants must not have certain infections such as hepatitis or tuberculosis or HIV that is not well controlled - Participants must not have another serious medical condition including a serious heart condition, such as congestive heart failure, unstable angina pectoris, or heart attack within the last three months - Participants must not have cancer of the central nervous system that is not stable - Participants must not be pregnant or breastfeeding - Participants must not use herbal supplements Advanced Solid Tumor Non-Small Cell Lung Cancer Colorecta Colorectal Cancer Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms null --- G12C --- --- G12C ---

This research study is designed to evaluate the effects of a dendritic cell (kind of white blood cell) vaccine for pancreatic cancer.

NCT03592888

Conditions

1. Pancreatic Ductal Adenocarcinoma

Interventions

1. Drug: mDC3/8-KRAS Vaccine

MeSH:Adenocarcinoma

Inclusion Criteria: - Pathologically-confirmed KRAS(G12D-), KRAS(G12V-), KRAS(G12R-) or KRAS(G12C-mutated) pancreatic ductal adenocarcinoma who are at high risk of relapse and have no evidence of disease. --- G12D --- --- G12V --- --- G12R --- --- G12C ---

This study is a Phase Ib, multi-center, open-label study of TNO155 in combination with spartalizumab or ribociclib with a dose escalation part followed by a dose expansion part in adult subjects with advanced solid tumors. These two treatment arms will enroll subjects in parallel to characterize the safety, tolerability, PK, PD and preliminary antitumor activity. The study treatment will be administered until the subject experiences unacceptable toxicity, progressive disease, and/or has treatment discontinued at the discretion of the Investigator or the subject, or due to withdrawal of consent.

NCT04000529

Conditions

1. Non-small Cell Lung Carcinoma
2. Head and Neck Squamous Cell Carcinoma
3. Esophageal SCC
4. Gastrointestinal Stromal Tumors
5. Colorectal Cancer

Interventions

1. Drug: TNO155
2. Drug: Spartalizumab
3. Drug: Ribociclib

MeSH:Carcinoma Squamous Cell Carcinoma of Head and Neck Gastrointestinal Stromal Tumors Carcinoma, Non-Small-Cell Lung Esophageal Squamous Cell Carcinoma

HPO:Carcinoma Gastrointestinal stroma tumor Non-small cell lung carcinoma

For TNO155 plus spartalizumab combination: i. Advanced EGFR WT, ALK WT, KRAS G12C NSCLC after progression on or intolerance to platinum-containing combination chemotherapy and after progression on anti-PD-1 or anti-PD-L1 therapy. --- G12C ---

The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of JNJ-74699157 in participants with advanced solid tumors harboring a kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation (Part 1: Dose escalation) and to determine the safety and preliminary antitumor activity of JNJ-74699157 at the RP2D regimen in participants with advanced solid tumors harboring a KRAS G12C mutation (Part 2: Dose expansion).

NCT04006301

Conditions

1. Neoplasms
2. Advanced Solid Tumors
3. Non-small Cell Lung Cancer
4. Colorectal Cancer

Interventions

1. Drug: JNJ-74699157

MeSH:Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms

HPO:Neoplasm of the large intestine Non-small cell lung carcinoma

A First-in-Human Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of JNJ-74699157 in Participants With Advanced Solid Tumors Harboring the KRAS G12C Mutation. --- G12C ---

First-in-Human Study of JNJ-74699157 in Participants With Tumors Harboring the KRAS G12C Mutation The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of JNJ-74699157 in participants with advanced solid tumors harboring a kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation (Part 1: Dose escalation) and to determine the safety and preliminary antitumor activity of JNJ-74699157 at the RP2D regimen in participants with advanced solid tumors harboring a KRAS G12C mutation (Part 2: Dose expansion). --- G12C ---

First-in-Human Study of JNJ-74699157 in Participants With Tumors Harboring the KRAS G12C Mutation The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of JNJ-74699157 in participants with advanced solid tumors harboring a kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation (Part 1: Dose escalation) and to determine the safety and preliminary antitumor activity of JNJ-74699157 at the RP2D regimen in participants with advanced solid tumors harboring a KRAS G12C mutation (Part 2: Dose expansion). --- G12C --- --- G12C ---

First-in-Human Study of JNJ-74699157 in Participants With Tumors Harboring the KRAS G12C Mutation The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of JNJ-74699157 in participants with advanced solid tumors harboring a kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation (Part 1: Dose escalation) and to determine the safety and preliminary antitumor activity of JNJ-74699157 at the RP2D regimen in participants with advanced solid tumors harboring a KRAS G12C mutation (Part 2: Dose expansion). --- G12C --- --- G12C --- --- G12C ---

AUC (0-last) is the area under the plasma concentration-time curve from time zero to last observed quantifiable concentration.. Part 1 and 2: Percentage of KRAS G12C Protein in Tumor Tissue Covalently Bound with JNJ-74699157 or its Metabolites. --- G12C ---

Percentage of kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) protein in tumor tissue covalently bound with JNJ-74699157 or its metabolites will be evaluated using mass spectroscopy.. Part 1: Overall Response Rate. --- G12C ---

Change from baseline in QTcF intervals will be assessed.. Inclusion Criteria: - Kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation in tumor tissue or blood - Histological documentation of disease: Part 1: Histologically or cytologically confirmed solid tumor malignancy that is metastatic or unresectable, Part 2: (a) unresectable, locally advanced (Stage IIIB) or metastatic (Stage IV) non-small cell lung cancer (NSCLC), (b) Solid tumor malignancy other than NSCLC that is metastatic or unresectable - Received or was ineligible for standard treatment options. --- G12C ---

Participants who have had complete surgical resection of or received stereotactic radiosurgery to less than or equal to (<=) 3 metastatic lesions will be permitted to enroll in the study within 14 days of such treatment if they have recovered from treatment, are clinically stable, and do not require prolonged systemic corticosteroid therapy as noted above - Prior treatment with an inhibitor specific to KRAS G12C - Prior solid organ transplantation - History of malignancy (other than the disease under study) within 2 years before the first administration of study drug. --- G12C ---

If any of these conditions exist, the investigator should discuss with the sponsor to determine participant eligibility Inclusion Criteria: - Kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation in tumor tissue or blood - Histological documentation of disease: Part 1: Histologically or cytologically confirmed solid tumor malignancy that is metastatic or unresectable, Part 2: (a) unresectable, locally advanced (Stage IIIB) or metastatic (Stage IV) non-small cell lung cancer (NSCLC), (b) Solid tumor malignancy other than NSCLC that is metastatic or unresectable - Received or was ineligible for standard treatment options. --- G12C ---

This study will evaluate JNJ-74699157, a potent and specific, orally bioavailable inhibitor of the glycine-to-cysteine (G12C) mutant KRAS protein, which is found in non-small cell lung cancers and other solid tumor types. --- G12C ---

This study will enroll participants with advanced solid tumors harboring the KRAS G12C mutation and will be conducted in 2 parts. --- G12C ---

This Phase 2 study evaluates the safety, pharmacokinetics, and clinical activity of MRTX849 in Combination with Pembrolizumab in Patients with Advanced Non-Small Cell Lung Cancer with KRAS G12C Mutation

NCT04613596

Conditions

1. Advanced Non-Small Cell Lung Cancer
2. Metastatic Cancer

Interventions

1. Drug: MRTX849 in Combination with Pembrolizumab

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung Neoplasm Metastasis

HPO:Neoplasm of the lung Non-small cell lung carcinoma

A Phase 2 Trial of MRTX849 in Combination With Pembrolizumab in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation. --- G12C ---

Phase 2 Trial of MRTX849 Plus Pembrolizumab for NSCLC With KRAS G12C Mutation KRYSTAL-7 This Phase 2 study evaluates the safety, pharmacokinetics, and clinical activity of MRTX849 in Combination with Pembrolizumab in Patients with Advanced Non-Small Cell Lung Cancer with KRAS G12C Mutation Evaluate the clinical activity of MRTX849 in combination with pembrolizumab. --- G12C ---

Phase 2 Trial of MRTX849 Plus Pembrolizumab for NSCLC With KRAS G12C Mutation KRYSTAL-7 This Phase 2 study evaluates the safety, pharmacokinetics, and clinical activity of MRTX849 in Combination with Pembrolizumab in Patients with Advanced Non-Small Cell Lung Cancer with KRAS G12C Mutation Evaluate the clinical activity of MRTX849 in combination with pembrolizumab. --- G12C --- --- G12C ---

Inclusion Criteria: - Histologically confirmed diagnosis of NSCLC (squamous or nonsquamous) with KRAS G12C mutation and known PD-L1 Tumor Proportion Score (TPS) score. --- G12C ---

Exclusion Criteria: - Prior systemic treatment for locally advanced or metastatic NSCLC including chemotherapy, immune checkpoint inhibitor therapy, or a therapy targeting KRAS G12C mutation (e.g., AMG 510). --- G12C ---

Advanced Non-Small Cell Lung Cancer Metastatic Cancer Lung Neoplasms Carcinoma, Non-Small-Cell Lung Neoplasm Metastasis This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 with Pembrolizumab in Patients with Advanced Non-Small Cell Lung Cancer with KRAS G12C Mutation. --- G12C ---

MRTX849 is an orally available small molecule inhibitor of KRAS G12C, and Pembrolizumab (KEYTRUDA®) is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. --- G12C ---

This phase II Lung-MAP treatment trial studies the effect of AMG 510 in treating non-squamous non-small cell lung cancer that is stage IV or has come back (recurrent) and has a specific mutation in the KRAS gene, known as KRAS G12C. Mutations in this gene may cause the cancer to grow. AMG 510, a targeted treatment against the KRAS G12C mutation, may help stop the growth of tumor cells.

NCT04625647

Conditions

1. Lung Adenocarcinoma
2. Lung Non-Small Cell Carcinoma
3. Recurrent Lung Non-Squamous Non-Small Cell Carcinoma
4. Stage IV Lung Cancer AJCC v8
5. Stage IVA Lung Cancer AJCC v8
6. Stage IVB Lung Cancer AJCC v8

Interventions

1. Drug: Sotorasib

MeSH:Carcinoma Lung Neoplasms Carcinoma, Non-Small-Cell Lung Adenocarcinoma of Lung

HPO:Carcinoma Neoplasm of the lung Non-small cell lung carcinoma

A Phase II Study of AMG 510 in Participants With Previously Treated Stage IV or Recurrent KRAS G12C Mutated Non-Squamous Non-Small Cell Lung Cancer (ECOG-ACRIN LUNG-MAP SUB-STUDY). --- G12C ---

Testing the Use of Targeted Treatment (AMG 510) for KRAS G12C Mutated Advanced Non-squamous Non-small Cell Lung Cancer (A Lung-MAP Treatment Trial) This phase II Lung-MAP treatment trial studies the effect of AMG 510 in treating non-squamous non-small cell lung cancer that is stage IV or has come back (recurrent) and has a specific mutation in the KRAS gene, known as KRAS G12C. --- G12C ---

Testing the Use of Targeted Treatment (AMG 510) for KRAS G12C Mutated Advanced Non-squamous Non-small Cell Lung Cancer (A Lung-MAP Treatment Trial) This phase II Lung-MAP treatment trial studies the effect of AMG 510 in treating non-squamous non-small cell lung cancer that is stage IV or has come back (recurrent) and has a specific mutation in the KRAS gene, known as KRAS G12C. --- G12C --- --- G12C ---

AMG 510, a targeted treatment against the KRAS G12C mutation, may help stop the growth of tumor cells. --- G12C ---

Lung cancer tumors become resistant to the first generation epidermal growth factor receptor (EGFR) inhibitors erlotinib or gefitinib by changing and increasing the activity of two cell signaling pathways: the cMET pathway and the EGFR pathway. Both resistance mechanisms can occur at the same time, in the same patient and even in the same tumor. This study combines a second generation EGFR inhibitor and a cMET inhibitor to block both these pathways in order to overcome resistance and treat this disease.

NCT01121575

Conditions

1. Non Small Cell Lung Cancer

Interventions

1. Drug: PF-02341066
2. Drug: PF-00299804
3. Drug: PF-02341066
4. Drug: PF-00299804

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

Sample analyses were performed in accordance to Good Laboratory Practice (GLP) guidance and included mutation detection for EGFR gene.. Number of Participants With KRAS Mutation (GLY12CYS) at Baseline. --- GLY12CYS ---

This phase II trial studies how well trametinib and docetaxel work in treating patients with stage IV KRAS mutation positive non-small cell lung cancer or cancer that has come back. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving trametinib with docetaxel may work better in treating non-small cell lung cancer.

NCT02642042

Conditions

1. KRAS Gene Mutation
2. Recurrent Lung Non-Small Cell Carcinoma
3. Stage IV Lung Non-Small Cell Cancer AJCC v7

Interventions

1. Drug: Docetaxel
2. Other: Laboratory Biomarker Analysis
3. Drug: Trametinib

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

Response rate (confirmed and unconfirmed complete and partial responses) in all KRAS mutant patients (both those with G12C mutations and those with non-G12C mutations). --- G12C ---

Response rate (confirmed and unconfirmed complete and partial responses) in all KRAS mutant patients (both those with G12C mutations and those with non-G12C mutations). --- G12C --- --- G12C ---

Response rate in patients with a G12C mutation. --- G12C ---

SECONDARY OBJECTIVES: I. To evaluate if trametinib plus docetaxel is consistent with promise of activity measured by the response rate in G12C KRAS mutation positive NSCLC patients following one or two prior systemic therapies. --- G12C ---

To assess the response rate of this combination in non-G12C KRAS mutation positive NSCLC patients. --- G12C ---

To assess progression-free survival within the G12C and non-G12C KRAS positive subgroups and the entire study population. --- G12C ---

To assess progression-free survival within the G12C and non-G12C KRAS positive subgroups and the entire study population. --- G12C --- --- G12C ---

V. To assess overall survival within G12C positive patients, non-G12C positive patients, and the entire study population. --- G12C ---

V. To assess overall survival within G12C positive patients, non-G12C positive patients, and the entire study population. --- G12C --- --- G12C ---

The purpose of this study is to determine whether carboplatin-paclitaxel-bevacizumab results in a prolonged progression free survival compared to cisplatin-pemetrexed as first line treatment in patients with KRAS mutated non-small cell lung cancer.

NCT02743923

Conditions

1. Carcinoma, Non-Small Cell Lung

Interventions

1. Drug: carboplatin
2. Drug: paclitaxel
3. Drug: Bevacizumab
4. Drug: Pemetrexed
5. Drug: cisplatin

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

Stratification for KRAS mutation (G12V versus G12C versus other). --- G12V --- --- G12C ---

outcome between G12V versus G12C versus other subtypes of KRAS mutations (mutational analysis on plasma and blood platelets).. --- G12V --- --- G12C ---

The two most common KRAS types are G12C in about 40% of cases, G12V in 18% and G12D in 15% of cases. --- G12C ---

Stratification for KRAS mutation (G12V versus G12C versus other) at randomization.. response by Crabb criteria (if applicable). --- G12V --- --- G12C ---

The purpose of this study is to see if TAS0612 is safe in participants with advanced or metastatic solid tumor cancer.

NCT04586270

Conditions

1. Advanced or Metastatic Solid Tumors

Interventions

1. Drug: TAS0612

MeSH:Neoplasms

HPO:Neoplasm

The levels/changes of the phospho-proteins will be assessed and reported for target modulation.. Inclusion Criteria: - Dose Escalation: have evidence of a solid tumor that is locally advanced and/or metastatic (excluding primary brain tumor) - Dose Expansion: have evidence of a solid tumor as outlined below that is locally advanced and/or metastatic (excluding primary brain tumor) - Cohort A: Human epidermal growth factor negative (HER2 negative) Breast Cancer with an NF1 mutation - Cohort B: Hormone receptor positive (HR+)/HER2 negative breast cancer after progression on endocrine therapy and a CDK4/6 inhibitor - Cohort C: PTEN loss or mutations - Cohort D: KRAS G12C mutation - Cohort E: KRAS G12D mutation - Have adequate organ function - Amenable to biopsy - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale Exclusion Criteria: - Participating in medical research not compatible with this study - Have not discontinued or recovered from previous treatments for cancer - Have a significant cardiac condition - Have untreated brain metastases - Have a primary brain tumor - Have a serious concomitant disorder - Unable to swallow or digest pills - Poorly controlled diabetes - Concomitant medications or substances that are strong inhibitors/inducers of CYP3A.Study Inclusion Criteria: - Dose Escalation: have evidence of a solid tumor that is locally advanced and/or metastatic (excluding primary brain tumor) - Dose Expansion: have evidence of a solid tumor as outlined below that is locally advanced and/or metastatic (excluding primary brain tumor) - Cohort A: Human epidermal growth factor negative (HER2 negative) Breast Cancer with an NF1 mutation - Cohort B: Hormone receptor positive (HR+)/HER2 negative breast cancer after progression on endocrine therapy and a CDK4/6 inhibitor - Cohort C: PTEN loss or mutations - Cohort D: KRAS G12C mutation - Cohort E: KRAS G12D mutation - Have adequate organ function - Amenable to biopsy - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale Exclusion Criteria: - Participating in medical research not compatible with this study - Have not discontinued or recovered from previous treatments for cancer - Have a significant cardiac condition - Have untreated brain metastases - Have a primary brain tumor - Have a serious concomitant disorder - Unable to swallow or digest pills - Poorly controlled diabetes - Concomitant medications or substances that are strong inhibitors/inducers of CYP3A.Study Advanced or Metastatic Solid Tumors Neoplasms null --- G12C ---

The levels/changes of the phospho-proteins will be assessed and reported for target modulation.. Inclusion Criteria: - Dose Escalation: have evidence of a solid tumor that is locally advanced and/or metastatic (excluding primary brain tumor) - Dose Expansion: have evidence of a solid tumor as outlined below that is locally advanced and/or metastatic (excluding primary brain tumor) - Cohort A: Human epidermal growth factor negative (HER2 negative) Breast Cancer with an NF1 mutation - Cohort B: Hormone receptor positive (HR+)/HER2 negative breast cancer after progression on endocrine therapy and a CDK4/6 inhibitor - Cohort C: PTEN loss or mutations - Cohort D: KRAS G12C mutation - Cohort E: KRAS G12D mutation - Have adequate organ function - Amenable to biopsy - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale Exclusion Criteria: - Participating in medical research not compatible with this study - Have not discontinued or recovered from previous treatments for cancer - Have a significant cardiac condition - Have untreated brain metastases - Have a primary brain tumor - Have a serious concomitant disorder - Unable to swallow or digest pills - Poorly controlled diabetes - Concomitant medications or substances that are strong inhibitors/inducers of CYP3A.Study Inclusion Criteria: - Dose Escalation: have evidence of a solid tumor that is locally advanced and/or metastatic (excluding primary brain tumor) - Dose Expansion: have evidence of a solid tumor as outlined below that is locally advanced and/or metastatic (excluding primary brain tumor) - Cohort A: Human epidermal growth factor negative (HER2 negative) Breast Cancer with an NF1 mutation - Cohort B: Hormone receptor positive (HR+)/HER2 negative breast cancer after progression on endocrine therapy and a CDK4/6 inhibitor - Cohort C: PTEN loss or mutations - Cohort D: KRAS G12C mutation - Cohort E: KRAS G12D mutation - Have adequate organ function - Amenable to biopsy - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale Exclusion Criteria: - Participating in medical research not compatible with this study - Have not discontinued or recovered from previous treatments for cancer - Have a significant cardiac condition - Have untreated brain metastases - Have a primary brain tumor - Have a serious concomitant disorder - Unable to swallow or digest pills - Poorly controlled diabetes - Concomitant medications or substances that are strong inhibitors/inducers of CYP3A.Study Advanced or Metastatic Solid Tumors Neoplasms null --- G12C --- --- G12D --- --- G12C ---

This is a phase 1/2, open label study of D-1553 single agent and combination treatment to assess the safety and tolerability, identify the MTD and RP2D, evaluate the PK properties and antitumor activities in subjects with advanced or metastatic solid tumor with KRasG12C mutation.

NCT04585035

Conditions

1. Solid Tumor, Adult
2. NSCLC
3. CRC

Interventions

1. Drug: D-1553
2. Drug: Other

MeSH:Neoplasms

HPO:Neoplasm

Plasma concentration of D-1553 as a single agent or in combination with other therapies in subjects wiht advanced or metastatic solid tumors with KRas G12C mutation.. null. --- G12C ---