Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Nervous System Diseases

Carcinoma, Non-Small-Cell Lung

Neoplasm Metastasis

Lung Neoplasms

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Antineoplastic Agents

All Drugs and Chemicals

Sotorasib

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Continuous once daily (QD) oral dosing (Days 1-21 each cycle) with or without food.

AMG 510

Intravenous (i.v.) infusion every 21 days (i.e. Day 1 of each 21-day cycle).

MVASI

Wade Iams, MD, MSCI

This is a multicenter, non-randomized, open-label, phase I/II study to evaluate the safety and tolerability of AMG 510 plus MVASI in subjects with advanced KRAS p.G12C mutant non-small cell lung cancer (NSCLC) with small, untreated brain metastases.

Each patient is scheduled to receive AMG 510 (KRASG12C inhibitor) in combination with MVASI (vascular endothelial growth factor \[VEGF\] inhibitor; bevacizumab biosimilar); both drugs will be provided by the study:

AMG 510:

Continuous once daily (QD) oral dosing (Days 1-21 each cycle) with or without food.

MVASI:

Intravenous (i.v.) infusion every 21 days (i.e. Day 1 of each 21-day cycle).

The study will be conducted in 2 parts. The dose expansion part of the study (Part 2) can open once the maximum tolerated dose (MTD) and/or a biologically active dose (e.g. recommended phase 2 dose \[RP2D\]) using a 3+3 study design has been determined in Part 1.

CNS response will be assessed using RANO-BM criteria, and non-CNS objective response will be based on Solid Tumor Response Criteria \[RECIST v1.1\] assessment of overall tumor burden at baseline versus that detected on subsequent CT/MRI re-scans. This includes a brain MRI on C2D1 (21 days) and a CT chest/abdomen/pelvis (C/A/P) at 6 weeks, then brain MRI at 15 weeks and CT C/A/P imaging at 12-16 weeks, and then every 4 cycles (every 12 weeks) while on study. It is intended that patients will be treated until disease progression or intolerable toxicity. Patients will be followed for survival for up to 18 months after ending study treatment.

A Phase I/II Study of AMG 510 in Combination With MVASI in Patients With Advanced, Unresectable or Metastatic KRAS G12C Mutant NSCLC With Asymptomatic Brain Metastasis

A Phase I/II Study of AMG 510 in Combination With MVASI in Patients With Advanced, Unresectable or Metastatic KRAS G12C Mutant NSCLC With Asymptomatic Brain Metastasis.

To determine the feasibility and safety of AMG 510 in combination with MVASI for the treatment of patients with KRAS G12C mutant NSCLC with asymptomatic, untreated brain metastases.

For patients enrolled in the dose exploration part of the study (anticipated to be the initial 9-18 patients participating in the study), whose participation will establish the recommended phase 2 dose (RP2D), dedicated surveillance and expedited reporting of Dose Limiting Toxicity (DLT) required for 21 days after initiating protocol-indicated treatment. Satisfactory completion of the physical exam and safety labs is required to help detect evidence of past or present DLT as having occurred during the first 21 days of protocol-indicated treatment.

To determine the CNS objective response and rate of salvage radiation to the CNS 18 weeks after therapy initiation.

The CNS objective response rate using Rando-BM will be evaluated at 18 weeks. Whether or not the patient requires salvage radiation therapy will be evaluated at 18 weeks

Safety and tolerability (phase I component).

Dedicated surveillance and expedited reporting of Dose Limiting Toxicity (DLT) is required for 21 days after initiating protocol-indicated treatment A minimum of 6 patients will be treated at the Maximum tolerated dose on the phase I portion of the study in order to obtain sufficient toxicity data prior to proceeding to the phase II evaluation of this regimen

CNS objective response, assessed using RANO-BM.

Initiation of salvage radiation therapy to the CNS at 18 weeks (phase II component).

To evaluate systemic disease control by progression free survival and overall survival.

Non-CNS overall response (ORR), assessed using RECIST v1.1.

Amgen

Criterium, Inc.

Digestive System Diseases

Rare Diseases

Sarcoma

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Anti-Infective Agents

Trifluridine

Panitumumab

Antimetabolites

Antiviral Agents

Participants will be administered trifluridine and tipiracil, or regorafenib

Panitumumab will be administered as intravenous (IV) infusion

Trifluridine and Tipiracil will be administered orally

Trifluridine and Tipiracil

Regorafenib

The aim of the study is to compare progression-free survival (PFS) in previously treated participants with Kirsten rat sarcoma (KRAS) p.G12C mutated colorectal cancer (CRC) receiving sotorasib 240 mg once daily (QD) and panitumumab vs investigator's choice (trifluridine and tipiracil, or regorafenib), and sotorasib 960 mg QD and panitumumab vs investigator's choice (trifluridine and tipiracil, or regorafenib).

Sotorasib and Panitumumab Versus Investigator's Choice for Participants With Kirsten Rat Sarcoma (KRAS) p.G12C Mutation

A Phase 3 Multicenter, Randomized, Open-label, Active-controlled Study of Sotorasib and Panitumumab Versus Investigator's Choice (Trifluridine and Tipiracil, or Regorafenib) for the Treatment of Previously Treated Metastatic Colorectal Cancer Subjects With Kirsten Rat Sarcoma (KRAS) p.G12C Mutation

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

A TEAE is any untoward medical occurrence in a clinical study participant following first dose of treatment irrespective of a causal relationship with the study treatment. Any clinically significant changes in vital signs and clinical laboratory tests following first dose will be recorded as TEAEs.

Item 3 of the BFI records a participants' fatigue on a scale from 0 to 10. Higher scores indicate a higher severity of fatigue. An increase in score from baseline indicates a worsening of fatigue. A decrease in score from baseline indicates an improvement in fatigue.

Item 3 of the BPI records a participants' pain on a scale from 1 to 10, where pain is mild (score of 1 to 4), moderate (score of 5 to 6), or severe (score of 7 to 10). An increase in score from baseline indicates a worsening of pain. A decrease in score from baseline indicates a lessening of pain.

The physical function domain of the EORTC QLQ-C30 assesses a participants' quality of life regarding their physical function on a scale from 1 to 4, with higher scores indicating a worse outcome. An increase in score from baseline indicates a worsening of physical functioning. A decrease in score from baseline indicates an improvement in physical functioning.

Questions 29 and 30 of the EORTC QLQ-C30 assess a participants' global health status on a scale from 1 to 7, with higher scores indicating a better outcome. An increase in score from baseline indicates an improvement in global health status. A decrease in score from baseline indicates a worsening in global health status.

The BFI is a questionnaire that includes 3 items to assess fatigue severity and 5 items to assess interference due to fatigue, with each item reported on a numeric rating scale from 0 to 10. Higher scores indicate a higher severity of fatigue. An increase in score from baseline indicates a worsening of fatigue. A decrease in score from baseline indicates an improvement in fatigue.

The BPI is a 9-item questionnaire which includes 2 body diagrams, four items to assess pain severity, four items to assess pain interference and one question about percentage of pain relief by analgesics. The level of pain and pain interference assessed can be divided into categories based on score of mild (1 to 4), moderate (5 to 6), and severe (7 to 10). An increase in score from baseline indicates a worsening of pain. A decrease in score from baseline indicates a lessening of pain.

The EORTC QLQ-C30 is a self-reporting 30-item generic instrument which assesses 5 functional domains (physical, role, emotional, cognitive, social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties), and a global health status/quality of life (QOL) scale. Higher scores indicate a worse outcome. An increase in score from baseline indicates a worsening of outcome. A decrease in score from baseline indicates an improvement in outcome.

The EQ-5D-5L questionnaire is a 2-page, standardized instrument for use as a measure of health outcome. It is comprised of a 5-dimension health status measure and a visual analogue scale. The 5-dimension health status measure evaluates: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression based on a 5-level scale: no problems, slight problems, moderate problems, severe problems, and extreme problems. The visual analogue scale records the participant's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'.

The GP5 from the FACT-G is a single item included in the Physical Well-Being subscale of the FACT-G. Responses to the item: "I am bothered by side effects of treatment" are rated on a 5-point Likert scale from "not at all" to "very much".

The PGIC scale consists of one item which measures the participants' perception of change in their condition relative to the beginning of the study. Responses are rated on a 7-item response scale ranging from very much improved to very much worse.

Skin and Connective Tissue Diseases

Breast Neoplasms

Lipid Regulating Agents

Bone Density Conservation Agents

Rosuvastatin Calcium

Calcium

Calcium, Dietary

Anticholesteremic Agents

Hypolipidemic Agents

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Enzyme Inhibitors

Rosuvastatin

A study to determine the effect of sotorasib on the pharmacokinetics (PK) of rosuvastatin, and to assess the PK of rosuvastatin when administered alone, in healthy participants.

Effect of Coadministration of Sotorasib on the Pharmacokinetics of Rosuvastatin in Healthy Participants

A Phase I, Open-label, Fixed Sequence Crossover Study to Investigate the Effect of Coadministration of Sotorasib on the Pharmacokinetics of Rosuvastatin, a Breast Cancer Resistance Protein Substrate, in Healthy Subjects

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

The pharmacokinetic (PK) parameters were determined using standard non-compartmental methods.

The PK parameters were determined using standard non-compartmental methods.

Any clinically significant changes in clinical laboratory tests, 12-lead electrocardiograms (ECGs), and vital signs results were recorded as AEs.

The safety population included all participants who received at least 1 dose of sotorasib or rosuvastatin and had at least 1 postdose safety assessment.

On Day 1, rosuvastatin was administered as a single 10 mg dose. All participants fasted overnight (at least 10 hours) until 4 hours postdose and refrained from consuming water for 1 hour prior to dosing and 2 hours postdose.

On Day 6, sotorasib was administered as a single 960 mg dose and was followed immediately by a single dose of 10 mg rosuvastatin. All participants fasted overnight (at least 10 hours) until 4 hours postdose and refrained from consuming water for 1 hour prior to dosing and 2 hours postdose.

Sotorasib + Rosuvastatin

On Day 1, rosuvastatin was administered as a single 10 mg dose. On Day 6, sotorasib was administered as a single 960 mg dose and was followed immediately by a single dose of 10 mg rosuvastatin. All participants fasted overnight (at least 10 hours) until 4 hours postdose and refrained from consuming water for 1 hour prior to dosing and 2 hours postdose.

All Participants

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Study Director

The ratios of geometric least squares means (GLSMs) and confidence intervals (CIs) were obtained by taking the exponential of the corresponding differences and CIs on the natural-log (ln) scale.

The PK population included all participants who received at least 1 dose of rosuvastatin or sotorasib and had evaluable PK data.

Maximum Observed Plasma Concentration (Cmax) of Rosuvastatin

The ratios of GLSMs and CIs were obtained by taking the exponential of the corresponding differences and CIs on the ln scale.

Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Rosuvastatin

AUC From Time Zero to Infinity (AUCinf) of Rosuvastatin

Number of Participants Reporting Any Treatment-Emergent Adverse Events (TEAEs)

Cmax of Sotorasib

AUClast of Sotorasib

AUCinf of Sotorasib

Overall Study

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Pembrolizumab

Carboplatin

Pemetrexed

Sotorasib administered in combination with carboplatin and pemetrexed.

Pembrolizumab administered in combination with carboplatin and pemetrexed.

Amgen Call Center

The primary objective of this study is to compare progression-free survival (PFS) in participants who receive sotorasib with platinum doublet chemotherapy versus participants who receive pembrolizumab with platinum doublet chemotherapy.

A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)

A Phase 3, Multicenter, Randomized, Open-label Study Evaluating Efficacy of Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Subjects With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers, Negative for PD-L1, and Positive for KRAS p.G12C (CodeBreaK 202)

PFS is defined as the time from randomization until the first documentation of radiologic disease progression or death due to any cause, whichever occurs first. Progression will be based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, per Blinded Independent Central Review (BICR).

Objective response is defined as the best overall response of complete response (CR) or partial response (PR), based on RECIST v1.1, per BICR.

OS is defined as the time from randomization until death due to any cause.

PFS2 is defined as the time from randomization to progression per investigator after initiation of new anticancer therapy or treatment beyond progression (ie, second progression) or death from any cause, whichever occurs first.

Measured by EuroQol-5 Dimension (EQ-5D-5L).

Duration of response is defined as the time from the first documentation of objective response until the first documentation of disease progression per BICR or death due to any cause, whichever occurs first.

Defined as the time from randomization to first evidence of PR or CR per BICR.

Defined as CR plus PR plus stable disease based on RECIST v1.1 per BICR.

Based on investigator tumor assessments per RECIST v1.1.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase I/II Study of AMG 510 in Combination With MVASI in Patients With Advanced, Unresectable or Metastatic KRAS G12C Mutant NSCLC With Asymptomatic Brain Metastasis	NCT05180422	Non Small Cell ...	AMG 510 MVASI	18 Years -	Criterium, Inc.
Sotorasib and Panitumumab Versus Investigator's Choice for Participants With Kirsten Rat Sarcoma (KRAS) p.G12C Mutation	NCT05198934	Colorectal Canc...	Sotorasib Panitumumab Trifluridine an... Regorafenib	18 Years - 100 Years	Amgen
Sotorasib and Panitumumab Versus Investigator's Choice for Participants With Kirsten Rat Sarcoma (KRAS) p.G12C Mutation	NCT05198934	Colorectal Canc...	Sotorasib Panitumumab Trifluridine an... Regorafenib	18 Years - 100 Years	Amgen
Effect of Coadministration of Sotorasib on the Pharmacokinetics of Rosuvastatin in Healthy Participants	NCT05045638	Healthy Partici...	Rosuvastatin Sotorasib	18 Years - 60 Years	Amgen
A Phase I/II Study of AMG 510 in Combination With MVASI in Patients With Advanced, Unresectable or Metastatic KRAS G12C Mutant NSCLC With Asymptomatic Brain Metastasis	NCT05180422	Non Small Cell ...	AMG 510 MVASI	18 Years -	Criterium, Inc.
Effect of Coadministration of Sotorasib on the Pharmacokinetics of Rosuvastatin in Healthy Participants	NCT05045638	Healthy Partici...	Rosuvastatin Sotorasib	18 Years - 60 Years	Amgen
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)	NCT05920356	Non-Small Cell ...	Sotorasib Pembrolizumab	18 Years - 100 Years	Amgen
Effect of Coadministration of Sotorasib on the Pharmacokinetics of Rosuvastatin in Healthy Participants	NCT05045638	Healthy Partici...	Rosuvastatin Sotorasib	18 Years - 60 Years	Amgen
A Phase I/II Study of AMG 510 in Combination With MVASI in Patients With Advanced, Unresectable or Metastatic KRAS G12C Mutant NSCLC With Asymptomatic Brain Metastasis	NCT05180422	Non Small Cell ...	AMG 510 MVASI	18 Years -	Criterium, Inc.

Spots Global Cancer Trial Database for amg 510

Every month we try and update this database with for amg 510 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for amg 510

Every month we try and update this database with for amg 510 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for amg 510 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.