A Phase 1/2, Study Evaluating the Safety, Tolerability, PK, and Efficacy of Sotorasib (AMG 510) in Subjects With Solid Tumors With a Specific KRAS Mutation (CodeBreaK 100)

• ClinicalTrials.gov Identifier: NCT03600883
• Recruitment Status: Active, not recruiting
• First Posted: July 26, 2018
• Last Update Posted: May 22, 2023
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: June 26, 2018
• First Posted Date: July 26, 2018
• Last Update Posted Date: May 22, 2023
• Actual Study Start Date: August 27, 2018
• Estimated Primary Completion Date: May 9, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 18, 2022)

• Primary: Number of subjects with treatment-emergent adverse events [ Time Frame: 24 Months ]
  Treatment-emergent adverse events will be a primary outcome measure for the following groups:

  • Phase 1 Dose Exploration Part 1 monotherapy
  • Phase 1 Dose Expansion Part 2 monotherapy
  • Phase 1 combination arm with sotorasib and anti PD-1/L1
  • Phase 1 monotherapy treatment naïve advanced NSCLC
  • Phase 2 monotherapy dose comparison
• Primary: Number of subjects with treatment-related adverse events [ Time Frame: 24 Months ]
  Treatment-related adverse events will be a primary outcome measure for the following groups:

  • Phase 1 Dose Exploration Part 1 monotherapy
  • Phase 1 Dose Expansion Part 2 monotherapy
  • Phase 1 combination arm with sotorasib and anti PD-1/L1
  • Phase 1 monotherapy treatment naïve advanced NSCLC
• Primary: Number of subjects with grade ≥3 treatment-emergent adverse events [ Time Frame: 24 Months ]
  Grade ≥3 treatment-emergent adverse events will be a primary outcome measure in the following group: - Phase 2 monotherapy dose comparison
• Primary: Number of subjects with serious adverse events [ Time Frame: 24 Months ]
  Serious adverse events will be a primary outcome measure in the following group: - Phase 2 monotherapy dose comparison
• Primary: Number of subjects with adverse events of interest [ Time Frame: 24 Months ]
  Adverse events of interest will be a primary outcome measure in the following group: - Phase 2 monotherapy dose comparison
• Primary: Number of subjects with clinically significant changes in vital signs [ Time Frame: Baseline to 24 Months ]
  Vital signs will be a primary outcome measure for the following groups:

  • Phase 1 Dose Exploration Part 1 monotherapy
  • Phase 1 Dose Expansion Part 2 monotherapy
  • Phase 1 combination arm with sotorasib and anti PD-1/L1
  • Phase 1 monotherapy treatment naïve advanced NSCLC
• Primary: Number of subjects with clinically significant changes in physical examination results [ Time Frame: Baseline to 24 Months ]
  Physical examinations will be a primary outcome measure for the following groups:

  • Phase 1 Dose Exploration Part 1 monotherapy
  • Phase 1 Dose Expansion Part 2 monotherapy
  • Phase 1 combination arm with sotorasib and anti PD-1/L1
• Primary: Number of subjects with clinically significant changes on electrocardiograms (ECGs) [ Time Frame: Baseline to 24 Months ]
  ECGs will be a primary outcome measure for the following groups:

  • Phase 1 Dose Exploration Part 1 monotherapy
  • Phase 1 Dose Expansion Part 2 monotherapy
  • Phase 1 combination arm with sotorasib and anti PD-1/L1
  • Phase 1 monotherapy treatment naïve advanced NSCLC
• Primary: Number of subjects with clinically significant changes in clinical laboratory values [ Time Frame: Baseline to 24 Months ]
  Abnormal clinical laboratory values will be a primary outcome measure for the following groups:

  • Phase 1 Dose Exploration Part 1 monotherapy
  • Phase 1 Dose Expansion Part 2 monotherapy
  • Phase 1 combination arm with sotorasib and anti PD-1/L1
  • Phase 1 monotherapy treatment naïve advanced NSCLC
• Primary: Number of subjects with dose-limiting toxicities (DLTs) [ Time Frame: 21 Days ]
  DLTs will be a primary outcome measure for the following groups:

  • Phase 1 Dose Exploration Part 1 monotherapy
  • Phase 1 Dose Expansion Part 2 monotherapy
  • Phase 1 combination arm with sotorasib and anti PD-1/L1
  • Phase 1 monotherapy treatment naïve advanced NSCLC
• Primary: Objective response rate (ORR) as assessed by RECIST 1.1 criteria [ Time Frame: 24 Months ]
  ORR will be a primary outcome measure in the following group:

  • Phase 1 monotherapy treatment naïve advanced NSCLC
  • Phase 2 monotherapy
  • Phase 2 monotherapy dose comparison
• Primary: Duration of response (DOR) as assessed by RECIST 1.1 criteria [ Time Frame: 24 Months ]
  DOR will be a primary outcome measure in the following group: - Phase 1 monotherapy treatment naïve advanced NSCLC
• Primary: Disease control as assessed by RECIST 1.1 criteria [ Time Frame: 24 Months ]
  Disease control will be a primary outcome measure in the following group: - Phase 1 monotherapy treatment naïve advanced NSCLC
• Primary: Duration of stable disease (SD) as assessed by RECIST 1.1 criteria [ Time Frame: 24 Months ]
  Duration of SD will be a primary outcome measure in the following group: - Phase 1 monotherapy treatment naïve advanced NSCLC
• Primary: Time to response (TTR) as assessed by RECIST 1.1 criteria [ Time Frame: 24 Months ]
  TTR will be a primary outcome measure in the following group: - Phase 1 monotherapy treatment naïve advanced NSCLC

Original Primary Outcome Measures (submitted: July 17, 2018)

• Number of Participants With Abnormal Laboratory Values [ Time Frame: 24 Months ]
• Number of subjects with clinically significant changes in vital signs. [ Time Frame: 24 Months ]
• Number of subjects with changes on ECG. [ Time Frame: 24 Months ]

Current Secondary Outcome Measures (submitted: February 18, 2022)

• Secondary: Plasma concentration (Cmax) of sotorasib [ Time Frame: 15 Weeks ]
  Cmax will be a secondary outcome measure for the following groups:

  • Phase 1 Dose Exploration Part 1 monotherapy
  • Phase 1 Dose Expansion Part 2 monotherapy
  • Phase 2 monotherapy
  • Phase 1 combination arm with sotorasib and anti PD-1/L1
  • Phase 1 monotherapy treatment naïve advanced NSCLC
  • Phase 2 monotherapy dose comparison
• Secondary: Plasma concentration (Cmax) of midazolam [ Time Frame: 16 Days ]
  Cmax of midazolam will be a secondary outcome measure for the subgroup of subjects who were administered midazolam in the following group: - Phase 1 monotherapy treatment naïve advanced NSCLC
• Secondary: Time to achieve Cmax (Tmax) of sotorasib [ Time Frame: 15 Weeks ]
  Tmax will be a secondary outcome measure for the following groups:

  • Phase 1 Dose Exploration Part 1 monotherapy
  • Phase 1 Dose Expansion Part 2 monotherapy
  • Phase 2 monotherapy
  • Phase 1 combination arm with sotorasib and anti PD-1/L1
  • Phase 1 monotherapy treatment naïve advanced NSCLC
• Secondary: Area under the plasma concentration-time curve (AUC) of sotorasib [ Time Frame: 15 Weeks ]
  AUC will be a secondary outcome measure for the following groups:

  • Phase 1 Dose Exploration Part 1 monotherapy
  • Phase 1 Dose Expansion Part 2 monotherapy
  • Phase 2 monotherapy
  • Phase 1 combination arm with sotorasib and anti PD-1/L1
  • Phase 1 monotherapy treatment naïve advanced NSCLC
  • Phase 2 monotherapy dose comparison
• Secondary: Area under the plasma concentration-time curve (AUC) of midazolam [ Time Frame: 16 Days ]
  AUC of midazolam will be a secondary outcome measure for the subgroup of subjects who were administered midazolam in the following group: - Phase 1 monotherapy treatment naïve advanced NSCLC
• Secondary: Clearance of midazolam from the plasma [ Time Frame: 16 Days ]
  Clearance of midazolam from the plasma will be a secondary outcome measure for the subgroup of subjects who were administered midazolam in the following group: - Phase 1 monotherapy treatment naïve advanced NSCLC
• Secondary: Terminal half-life (t1/2) of midazolam [ Time Frame: 16 Days ]
  t1/2 of midazolam will be a secondary outcome measure for the subgroup of subjects who were administered midazolam in the following group: - Phase 1 monotherapy treatment naïve advanced NSCLC
• Secondary: Objective response rate (ORR) as assessed by RECIST 1.1 criteria [ Time Frame: 24 Months ]
  ORR will be a secondary outcome measure for the following groups:

  • Phase 1 Dose Exploration Part 1 monotherapy
  • Phase 1 Dose Expansion Part 2 monotherapy
  • Phase 1 combination arm with sotorasib and anti PD-1/L1
• Secondary: Duration of response (DOR) as assessed by RECIST 1.1 criteria [ Time Frame: 24 Months ]
  DOR will be a secondary outcome measure for the following groups:

  • Phase 1 Dose Exploration Part 1 monotherapy
  • Phase 1 Dose Expansion Part 2 monotherapy
  • Phase 2 monotherapy
  • Phase 1 combination arm with sotorasib and anti PD-1/L1
  • Phase 2 monotherapy dose comparison
• Secondary: Disease control as assessed by RECIST 1.1 criteria [ Time Frame: 24 Months ]
  DOR will be a secondary outcome measure for the following groups:

  • Phase 1 Dose Exploration Part 1 monotherapy
  • Phase 1 Dose Expansion Part 2 monotherapy
  • Phase 2 monotherapy
  • Phase 1 combination arm with sotorasib and anti PD-1/L1
  • Phase 2 monotherapy dose comparison
• Secondary: Progression-free survival (PFS) as assessed by RECIST 1.1 criteria [ Time Frame: 24 Months ]
  PFS will be a secondary outcome measure for the following groups:

  • Phase 1 Dose Exploration Part 1 monotherapy
  • Phase 1 Dose Expansion Part 2 monotherapy
  • Phase 2 monotherapy
  • Phase 1 combination arm with sotorasib and anti PD-1/L1
  • Phase 2 monotherapy dose comparison
  • Phase 1 monotherapy treatment naïve advanced NSCLC
• Secondary: Duration of stable disease (SD) as assessed by RECIST 1.1 criteria [ Time Frame: 24 Months ]
  Duration of SD will be a secondary outcome measure for the following groups:

  • Phase 1 Dose Exploration Part 1 monotherapy
  • Phase 1 Dose Expansion Part 2 monotherapy
  • Phase 1 combination arm with sotorasib and anti PD-1/L1
• Secondary: Depth of response (best percentage change from baseline in lesion sum diameters) as assessed by RECIST 1.1 criteria [ Time Frame: Baseline to 24 Months ]
  Depth of response will be a secondary outcome measure for the following group: - Phase 2 monotherapy dose comparison
• Secondary: Time to response (TTR) as assessed by RECIST 1.1 criteria [ Time Frame: 24 Months ]
  DOR will be a secondary outcome measure for the following groups:

  • Phase 1 Dose Exploration Part 1 monotherapy
  • Phase 1 Dose Expansion Part 2 monotherapy
  • Phase 2 monotherapy
  • Phase 1 combination arm with sotorasib and anti PD-1/L1
  • Phase 2 monotherapy dose comparison
• Secondary: Overall survival (OS) [ Time Frame: 24 Months ]
  OS will be a secondary outcome measure for the following groups:

  • Phase 1 Dose Exploration Part 1 monotherapy
  • Phase 1 Dose Expansion Part 2 monotherapy
  • Phase 2 monotherapy
  • Phase 1 combination arm with sotorasib and anti PD-1/L1
  • Phase 2 monotherapy dose comparison
  • Phase 1 monotherapy treatment naïve advanced NSCLC
• Secondary: sotorasib exposure and QTc interval relationship [ Time Frame: 24 Months ]
  sotorasib exposure and QTc interval relationship will be a secondary outcome measure for the following groups:

  • Phase 1 Dose Exploration Part 1 monotherapy
  • Phase 1 Dose Expansion Part 2 monotherapy
• Secondary: Progression-free survival (PFS) at 6 months [ Time Frame: 6 Months ]
  PFS at 6 months will be a secondary outcome measure for the following group: - Phase 2 monotherapy
• Secondary: Progression-free survival (PFS) at 12 months [ Time Frame: 12 Months ]
  PFS at 12 months will be a secondary outcome measure for the following group: - Phase 2 monotherapy
• Secondary: Overall survival (OS) at 12 months [ Time Frame: 12 Months ]
  OS at 12 months will be a secondary outcome measure for the following group: - Phase 2 monotherapy
• Secondary: Number of subjects with treatment-emergent adverse events [ Time Frame: 24 Months ]
  Treatment-emergent adverse events will be a secondary outcome measure for the following group: - Phase 2 monotherapy
• Secondary: Number of subjects with grade ≥3 treatment-emergent adverse events [ Time Frame: 24 Months ]
  Grade ≥3 treatment-emergent adverse events will be a secondary outcome measure for the following group: - Phase 2 monotherapy
• Secondary: Impact of treatment on disease-related symptoms and health related quality of life (HRQOL) as assessed by EORTC QLQ-C30 [ Time Frame: 24 Months ]
  Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group: - Phase 2 monotherapy dose comparison
• Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by disease-specific modules Quality-of-Life Questionnaire Lung Cancer Module (QLQ LC13) [ Time Frame: 24 Months ]
  Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group: - Phase 2 monotherapy dose comparison
• Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by non-small cell lung cancer symptom assessment questionnaire (NSCLC SAQ) for NSCLC [ Time Frame: 24 Months ]
  Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group: - Phase 2 monotherapy dose comparison
• Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by Patient Global Impression of Severity (PGIS) [ Time Frame: 24 Months ]
  Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group: - Phase 2 monotherapy dose comparison
• Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by Patient Global Impression of Change (PGIC) in cough, dyspnea and chest pain for NSCLC [ Time Frame: 24 Months ]
  Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group: - Phase 2 monotherapy dose comparison
• Secondary: Treatment-related symptoms and impact on the subject as assessed by EORTC QLQ-C30 [ Time Frame: 24 Months ]
  Treament related symptoms and impact on the subject will be a secondary outcome measure for the following group: - Phase 2 monotherapy dose comparison
• Secondary: Treatment-related symptoms and impact on the subject as assessed by selected questions from the Patient-reported Outcome of the Common Terminology Criteria for Adverse Events (PRO-CTCAE library) [ Time Frame: 24 Months ]
  Treatment-related symptoms and impact on the subject will be a secondary outcome measure for the following group: - Phase 2 monotherapy dose comparison
• Secondary: Treatment-related symptoms and impact on the subject as assessed by a single item about symptom bother, item GP5 of the Functional Assessment of Cancer Therapy - General (FACT-G) [ Time Frame: 24 Months ]
  Treatment-related symptoms and impact on the subject will be a secondary outcome measure for the following group: - Phase 2 monotherapy dose comparison
• Secondary: Change from baseline in physical function as assessed by EORTC QLQ-C30 [ Time Frame: Baseline to 24 Months ]
  Treatment-related symptoms and impact on the subject will be a secondary outcome measure for the following group: - Phase 2 monotherapy dose comparison

Original Secondary Outcome Measures (submitted: July 17, 2018)

• Plasma concentration (Cmax) [ Time Frame: 24 Months ]
• Time to achieve Cmax (tmax) [ Time Frame: 24 Months ]
• Area under the plasma concentration-time curve (AUC) [ Time Frame: 24 Months ]
• Objective response rate [ Time Frame: 24 months ]
• Duration of overall response [ Time Frame: 24 Months ]
• Progression-free survival [ Time Frame: 24 Months ]
• Duration of stable disease [ Time Frame: 24 Months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 1/2, Study Evaluating the Safety, Tolerability, PK, and Efficacy of Sotorasib (AMG 510) in Subjects With Solid Tumors With a Specific KRAS Mutation (CodeBreaK 100)
• Official Title: A Phase 1/2, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Sotorasib (AMG 510) Monotherapy in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation and Sotorasib (AMG 510) Combination Therapy in Subjects With Advanced NSCLC With KRAS p.G12C Mutation (CodeBreaK 100)

Brief Summary

Evaluate the safety and tolerability of sotorasib in adult subjects with KRAS p.G12C mutant advanced solid tumors.

Estimate the maximum tolerated dose (MTD) and/or a recommended phase 2 dose (RP2D) in adult subjects with KRAS p.G12C mutant advanced solid tumors.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: KRAS p.G12C Mutant Advanced Solid Tumors

Intervention

• Drug: sotorasib
  Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
• Drug: Anti PD-1/L1
  Administered as an intravenous (IV) infusion
• Drug: Midazolam
  Administered as an oral hydrochloride (HCI) syrup

Study Arms

• Experimental: Phase 1 Dose Exploration Part 1 monotherapy

  Cohorts with food effect and alternative dosing regimens

  Enrollment into the dose exploration cohorts may be from any eligible solid tumor type. Dose escalation will begin with 2-4 subjects treated at the lowest planned dose level of 180 mg. If no DLT is observed, dose escalation will continue to the next planned dose cohort

  Intervention: Drug: sotorasib
• Experimental: Phase 1 Dose Expansion Part 2 monotherapy
  Upon completing the dose exploration part of the study, dose expansion may proceed with 3 groups consisting of subjects with KRAS p.G12C mutant advanced solid tumors. Dose expansion in these 3 groups may be done concurrently
  Intervention: Drug: sotorasib
• Experimental: Phase 2 monotherapy
  Additional subjects will be enrolled in the dose expansion to confirm the recommended phase 2 dose. Enrollment into phase 2 will be opened after confirmation of the recommended phase 2 dose
  Intervention: Drug: sotorasib
• Experimental: Phase 1 combination arm with sotorasib and anti PD-1/L1
  Additional subjects will be enrolled into the combination arm with sotorasib in combination with an anti (PD-1/L1)
  Interventions:

  • Drug: sotorasib
  • Drug: Anti PD-1/L1
• Experimental: Phase 1 monotherapy treatment naive advanced NSCLC
  Separate cohort of part 1 dose expansion subjects to evaluate the safety and clinical activity of sotorasib administered orally once daily in subjects with previously untreated advanced non-small cell lung cancer (NSCLC). Drug-drug interaction will be evaluated in 6 of the subjects enrolled in the treatment naive cohort by adding Midazolam alone on Day -1 and in combination with sotorasib on Day 15 of Cycle 1, where each cycle is 21 days.
  Interventions:

  • Drug: sotorasib
  • Drug: Midazolam
• Experimental: Phase 2 monotherapy dose comparison
  Subjects with NSCLC will be enrolled in a dose comparison study evaluating safety and efficacy
  Intervention: Drug: sotorasib

Publications *

• Canon J, Rex K, Saiki AY, Mohr C, Cooke K, Bagal D, Gaida K, Holt T, Knutson CG, Koppada N, Lanman BA, Werner J, Rapaport AS, San Miguel T, Ortiz R, Osgood T, Sun JR, Zhu X, McCarter JD, Volak LP, Houk BE, Fakih MG, O'Neil BH, Price TJ, Falchook GS, Desai J, Kuo J, Govindan R, Hong DS, Ouyang W, Henary H, Arvedson T, Cee VJ, Lipford JR. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature. 2019 Nov;575(7781):217-223. doi: 10.1038/s41586-019-1694-1. Epub 2019 Oct 30.
• Skoulidis F, Li BT, Dy GK, Price TJ, Falchook GS, Wolf J, Italiano A, Schuler M, Borghaei H, Barlesi F, Kato T, Curioni-Fontecedro A, Sacher A, Spira A, Ramalingam SS, Takahashi T, Besse B, Anderson A, Ang A, Tran Q, Mather O, Henary H, Ngarmchamnanrith G, Friberg G, Velcheti V, Govindan R. Sotorasib for Lung Cancers with KRAS p.G12C Mutation. N Engl J Med. 2021 Jun 24;384(25):2371-2381. doi: 10.1056/NEJMoa2103695. Epub 2021 Jun 4.
• Fakih MG, Kopetz S, Kuboki Y, Kim TW, Munster PN, Krauss JC, Falchook GS, Han SW, Heinemann V, Muro K, Strickler JH, Hong DS, Denlinger CS, Girotto G, Lee MA, Henary H, Tran Q, Park JK, Ngarmchamnanrith G, Prenen H, Price TJ. Sotorasib for previously treated colorectal cancers with KRASG12C mutation (CodeBreaK100): a prespecified analysis of a single-arm, phase 2 trial. Lancet Oncol. 2022 Jan;23(1):115-124. doi: 10.1016/S1470-2045(21)00605-7. Epub 2021 Dec 15.
• Hong DS, Fakih MG, Strickler JH, Desai J, Durm GA, Shapiro GI, Falchook GS, Price TJ, Sacher A, Denlinger CS, Bang YJ, Dy GK, Krauss JC, Kuboki Y, Kuo JC, Coveler AL, Park K, Kim TW, Barlesi F, Munster PN, Ramalingam SS, Burns TF, Meric-Bernstam F, Henary H, Ngang J, Ngarmchamnanrith G, Kim J, Houk BE, Canon J, Lipford JR, Friberg G, Lito P, Govindan R, Li BT. KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors. N Engl J Med. 2020 Sep 24;383(13):1207-1217. doi: 10.1056/NEJMoa1917239. Epub 2020 Sep 20.
• Zhao Y, Murciano-Goroff YR, Xue JY, Ang A, Lucas J, Mai TT, Da Cruz Paula AF, Saiki AY, Mohn D, Achanta P, Sisk AE, Arora KS, Roy RS, Kim D, Li C, Lim LP, Li M, Bahr A, Loomis BR, de Stanchina E, Reis-Filho JS, Weigelt B, Berger M, Riely G, Arbour KC, Lipford JR, Li BT, Lito P. Diverse alterations associated with resistance to KRAS(G12C) inhibition. Nature. 2021 Nov;599(7886):679-683. doi: 10.1038/s41586-021-04065-2. Epub 2021 Nov 10.
• Strickler JH, Satake H, George TJ, Yaeger R, Hollebecque A, Garrido-Laguna I, Schuler M, Burns TF, Coveler AL, Falchook GS, Vincent M, Sunakawa Y, Dahan L, Bajor D, Rha SY, Lemech C, Juric D, Rehn M, Ngarmchamnanrith G, Jafarinasabian P, Tran Q, Hong DS. Sotorasib in KRAS p.G12C-Mutated Advanced Pancreatic Cancer. N Engl J Med. 2023 Jan 5;388(1):33-43. doi: 10.1056/NEJMoa2208470. Epub 2022 Dec 21.
• Lanman BA, Allen JR, Allen JG, Amegadzie AK, Ashton KS, Booker SK, Chen JJ, Chen N, Frohn MJ, Goodman G, Kopecky DJ, Liu L, Lopez P, Low JD, Ma V, Minatti AE, Nguyen TT, Nishimura N, Pickrell AJ, Reed AB, Shin Y, Siegmund AC, Tamayo NA, Tegley CM, Walton MC, Wang HL, Wurz RP, Xue M, Yang KC, Achanta P, Bartberger MD, Canon J, Hollis LS, McCarter JD, Mohr C, Rex K, Saiki AY, San Miguel T, Volak LP, Wang KH, Whittington DA, Zech SG, Lipford JR, Cee VJ. Discovery of a Covalent Inhibitor of KRASG12C (AMG 510) for the Treatment of Solid Tumors. J Med Chem. 2020 Jan 9;63(1):52-65. doi: 10.1021/acs.jmedchem.9b01180. Epub 2019 Dec 24.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 30, 2022): 713
• Original Estimated Enrollment (submitted: July 17, 2018): 60
• Estimated Study Completion Date: May 9, 2027
• Estimated Primary Completion Date: May 9, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Men or women greater than or equal to 18 years old.
• Pathologically documented, locally-advanced or metastatic malignancy with, KRAS p.G12C mutation identified through molecular testing.

Exclusion Criteria

• Active brain metastases from non-brain tumors.
• Myocardial infarction within 6 months of study day 1.
• Gastrointestinal (GI) tract disease causing the inability to take oral medication.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 100 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Brazil, Canada, France, Germany, Greece, Hungary, Japan, Korea, Republic of, Portugal, Romania, Spain, Switzerland, United States

Administrative Information

• NCT Number: NCT03600883
• Other Study ID Numbers: 20170543
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• URL: https://www.amgen.com/datasharing

• Current Responsible Party: Amgen
• Original Responsible Party: Same as current
• Current Study Sponsor: Amgen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: MD; Amgen

• PRS Account: Amgen
• Verification Date: May 2023