History of Changes for Study: NCT04933695

Version	Submitted Date	Changes
1	June 14, 2021	None (earliest Version on record)
2	October 13, 2021	Study Status
3	December 8, 2021	Study Status, Arms and Interventions, Study Identification, Contacts/Locations, Eligibility and Study Description
4	January 7, 2022	Study Status and Contacts/Locations
5	January 25, 2022	Study Status and Contacts/Locations
6	February 2, 2022	Recruitment Status, Study Status, Contacts/Locations and Oversight
7	February 17, 2022	Contacts/Locations and Study Status
8	March 2, 2022	Study Status and Contacts/Locations
9	March 30, 2022	Contacts/Locations and Study Status
10	April 6, 2022	Study Status and Contacts/Locations
11	April 13, 2022	Contacts/Locations and Study Status
12	May 24, 2022	Contacts/Locations, Study Status and Eligibility
13	June 8, 2022	Contacts/Locations and Study Status
14	June 17, 2022	Contacts/Locations and Study Status
15	June 22, 2022	Contacts/Locations and Study Status
16	July 6, 2022	Study Status and Contacts/Locations
17	July 27, 2022	Contacts/Locations and Study Status
18	August 3, 2022	Study Status and Contacts/Locations
19	August 11, 2022	Recruitment Status, Study Status and Contacts/Locations
20	November 29, 2022	Contacts/Locations and Study Status
21	February 3, 2023	Study Status, Study Design and Contacts/Locations
22	April 20, 2023	Study Status
23	October 10, 2023	Study Status

Unique Protocol ID:

20190288

Brief Title:

A Study of Sotorasib (AMG 510) in Participants With Stage IV NSCLC Whose Tumors Harbor a KRAS p.G12C Mutation in Need of First-line Treatment (CodeBreaK201)

Official Title:

A Phase 2, Multicenter, Open-label Study of Sotorasib (AMG 510) in Subjects With Stage IV NSCLC Whose Tumors Harbor a KRAS G12C Mutation in Need of First-line Treatment (CodeBreaK 201)

Secondary IDs:

2021-002638-18 [EudraCT Number]

Record Verification:

April 2023

October 2023

Overall Status:

Active, not recruiting

Study Start:

January 28, 2022

Primary Completion:

August 23, 2024 [Anticipated]

November 14, 2024 [Anticipated]

Study Completion:

August 23, 2024 [Anticipated]

November 14, 2024 [Anticipated]

First Submitted:

June 14, 2021

First Submitted that
Met QC Criteria:

June 14, 2021

First Posted:

June 22, 2021 [Actual]

Last Update Submitted that
Met QC Criteria:

April 20, 2023

October 10, 2023

Last Update Posted:

April 21, 2023 [Actual]

October 11, 2023 [Actual]

Brief Summary:

The main objective of this study is to evaluate the tumor objective response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in participants who receive sotorasib at either 960 mg daily or 240 mg daily whose tumors are programmed death-ligand 1 (PD-L1) Tumor Proportion Score (TPS) < 1% and/or harbor a serine/threonine kinase 11 (STK11) co-mutation, in a subgroup of participants with PD-L1 < 1% and in a subgroup of participants with STK11 co-mutation.

Detailed Description:

Arms

Assigned Interventions

Experimental: Sotorasib: 960 mg Daily

Participants with metastatic non-small cell lung cancer (NSCLC) with Kirsten rat sarcoma (KRAS) p.G12C mutation whose tumors express < 1% programmed death-ligand 1 (PD-L1) and/or serine/threonine kinase 11 (STK11) mutation in need of first line treatment will be administered sotorasib 960 mg daily. Participants will be stratified by known presence of STK11 mutation.

Drug: Sotorasib

Oral tablet

Other Names:

AMG 510
LUMYKRAS
LUMAKRAS

Experimental: Sotorasib: 240 mg Daily

Participants with metastatic non-small cell lung cancer (NSCLC) with Kirsten rat sarcoma (KRAS) p.G12C mutation whose tumors express < 1% programmed death-ligand 1 (PD-L1) and/or serine/threonine kinase 11 (STK11) mutation in need of first line treatment will be administered sotorasib 240 mg daily. Participants will be stratified by known presence of STK11 mutation.

Drug: Sotorasib

Oral tablet

Other Names:

AMG 510
LUMYKRAS
LUMAKRAS

Primary Outcome Measures:

Objective Response Rate (OR)
[ Time Frame: Up to 6 years ]

OR is defined as the total of Complete Response (CR) and Partial Response (PR).

Secondary Outcome Measures:

Disease Control Rate
[ Time Frame: Up to 6 years ]

Duration of Reponse (DOR)
[ Time Frame: Up to 6 years ]

Time to Response (TTR)
[ Time Frame: Up to 6 years ]

Progression-free Survival (PFS)
[ Time Frame: Up to 6 years ]

Overall Survival (OS)
[ Time Frame: Up to 6 years ]

Number of Participants with a Treatment-emergent Adverse Event (TEAE)
[ Time Frame: Day 1 up to Month 13 ]

Number of Participants with a Treatment-related Adverse Event
[ Time Frame: Day 1 up to Month 13 ]

Number of Participants with a Clinically Significant Change from Baseline in Vital Signs
[ Time Frame: Baseline (Screening; up to 28 days pre-dose) up to Month 13 ]

Number of Participants with a Clinically Significant Change from Baseline in Electrocardiograms (ECGs)
[ Time Frame: Baseline (Screening; up to 28 days pre-dose) up to Month 13 ]

10.

Number of Participants with a Clinically Significant Change from Baseline in Clinical Laboratory Tests
[ Time Frame: Baseline (Screening; up to 28 days pre-dose) up to Month 13 ]

11.

Maximum Plasma Concentration (Cmax) of Sotorasib
[ Time Frame: Day 1 up to Month 3 ]

12.

Time to Reach Maximum Plasma Concentration (tmax) of Sotorasib
[ Time Frame: Day 1 up to Month 3 ]

13.

Area Under the Plasma Concentration-time Curve (AUC) of Sotorasib
[ Time Frame: Day 1 up to Month 3 ]

Minimum Age:

18 Years

Maximum Age:

Sex:

All

Gender Based:

Accepts Healthy Volunteers:

Criteria:

Inclusion Criteria:

Adult (= or > 18 years old) with NSCLC
Untreated Stage IV metastatic disease. Participants who received adjuvant or neoadjuvant anti-tumor therapy are eligible if the adjuvant/neoadjuvant therapy was completed greater than 12 months prior to the development of metastatic stage IV disease
Pathologically documented metastatic NSCLC with KRAS G12C mutation (local confirmation)
Programmed death-ligand 1 (PD-L1) TPS Score < 1% and/or serine/threonine kinase 11 (STK11) co-mutation (local confirmation)
Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
No active brain metastases
Measurable disease per investigator interpretation using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

Exclusion Criteria:

Mixed small-cell lung cancer and NSCLC histology
Myocardial Infarction within 6 months of study Day 1
Use of proton-pump inhibitors (PPIs), histamine (H2) receptor antagonists (H2RA), strong inducers of cytochrome P450 (CYP) 3A4 (CYP3A4) or known CYP3A4 sensitive substrates or P-gp substrates
Therapeutic or palliative radiation therapy within 2 weeks of study day 1
Unable to take oral medication
Unable to receive both iodinated contrast for computed tomography (CT) scans and gadolinium contrast for magnetic resonance imagine (MRI) scans

Inclusion Criteria:

Adult (= or > 18 years old) with NSCLC
Untreated Stage IV metastatic disease. Participants who received adjuvant or neoadjuvant anti-tumor therapy are eligible if the adjuvant/neoadjuvant therapy was completed greater than 12 months prior to the development of metastatic stage IV disease
Pathologically documented metastatic NSCLC with KRAS G12C mutation (local confirmation)
Programmed death-ligand 1 (PD-L1) TPS Score < 1% and/or serine/threonine kinase 11 (STK11) co-mutation (local confirmation)
Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
No active brain metastases
Measurable disease per investigator interpretation using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

Exclusion Criteria:

Mixed small-cell lung cancer and NSCLC histology
Myocardial Infarction within 6 months of study Day 1
Use of proton-pump inhibitors (PPIs), histamine (H2) receptor antagonists (H2RA), strong inducers of cytochrome P450 (CYP) 3A4 (CYP3A4) or known CYP3A4 sensitive substrates or P-gp substrates
Therapeutic or palliative radiation therapy within 2 weeks of study day 1
Unable to take oral medication
Unable to receive both iodinated contrast for computed tomography (CT) scans and gadolinium contrast for magnetic resonance imagine (MRI) scans

Contacts/Locations

Plan to Share IPD:

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

Supporting Information:

Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)

Supporting Information:

Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
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.

Time Frame:

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.

Access Criteria:

URL: http://www.amgen.com/datasharing