Clinical Trial Results:
A Multicenter, Open-label, Single-arm, Expanded Access Protocol of Sotorasib (AMG 510) for the Treatment of Subjects in Select European Countries with Previously Treated Locally Advanced and Unresectable or Metastatic Non-small Cell Lung Cancer with KRAS p.G12C Mutation
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Summary
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EudraCT number |
2020-005279-11 |
Trial protocol |
IT ES |
Global end of trial date |
11 Aug 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
21 May 2023
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First version publication date |
21 May 2023
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
20190442
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Amgen Inc.
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Sponsor organisation address |
One Amgen Center Drive, Thousand Oaks, CA, United States,
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Public contact |
IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, medinfo@amgen.com
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Scientific contact |
IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, medinfo@amgen.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
11 Aug 2022
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
11 Aug 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objectives of this study were to provide expanded access and to characterize the safety profile of sotorasib in participants with previously treated locally advanced unresectable/metastatic non-small cell lung cancer (NSCLC) with Kirsten rat sarcoma viral oncogene homolog (KRAS) p.G12C mutation.
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Protection of trial subjects |
This study was conducted in accordance with International Council for Harmonisation (ICH) Good Clinical Practice (GCP) regulations/guidelines.
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Background therapy |
- | ||
Evidence for comparator |
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Actual start date of recruitment |
08 Jul 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Italy: 75
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Country: Number of subjects enrolled |
Spain: 44
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Worldwide total number of subjects |
119
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EEA total number of subjects |
119
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
45
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From 65 to 84 years |
72
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85 years and over |
2
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Recruitment
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Recruitment details |
This study was conducted at 40 centers in Italy and Spain from 08 July 2021 to 11 August 2022. | ||||||||||||||
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Pre-assignment
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Screening details |
A total of 130 participants were screened for enrollment into this study. Of those, 119 participants were enrolled. A total of 118 participants received at least 1 dose of sotorasib. | ||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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Sotorasib | ||||||||||||||
Arm description |
Participants received sotorasib 960 mg orally once daily (QD). Treatment cycles were 28 days long, with no treatment-free intervals. Participants were treated with sotorasib until disease progression, intolerance of protocol treatment, start of another anti-cancer therapy, death, withdrawal of informed consent, or for up to 6 months (if in accordance with local laws and regulations) of treatment for an individual participant after sotorasib received marketing authorization approval for the treatment of NSCLC in the participant's country, whichever occurred first. Participants with previously treated locally advanced unresectable/metastatic NSCLC with KRAS p.G12C mutation who were not eligible or did not have the opportunity to enroll in an ongoing sotorasib interventional clinical study and who met the eligibility criteria outlined in the protocol were considered for participation in this study. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Sotorasib
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Investigational medicinal product code |
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Other name |
AMG 510 Lumakras® Lumykras®
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received sotorasib 960 mg once daily (QD) in each 28 day cycle.
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Baseline characteristics reporting groups
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Reporting group title |
Sotorasib
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Reporting group description |
Participants received sotorasib 960 mg orally once daily (QD). Treatment cycles were 28 days long, with no treatment-free intervals. Participants were treated with sotorasib until disease progression, intolerance of protocol treatment, start of another anti-cancer therapy, death, withdrawal of informed consent, or for up to 6 months (if in accordance with local laws and regulations) of treatment for an individual participant after sotorasib received marketing authorization approval for the treatment of NSCLC in the participant's country, whichever occurred first. Participants with previously treated locally advanced unresectable/metastatic NSCLC with KRAS p.G12C mutation who were not eligible or did not have the opportunity to enroll in an ongoing sotorasib interventional clinical study and who met the eligibility criteria outlined in the protocol were considered for participation in this study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Sotorasib
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Reporting group description |
Participants received sotorasib 960 mg orally once daily (QD). Treatment cycles were 28 days long, with no treatment-free intervals. Participants were treated with sotorasib until disease progression, intolerance of protocol treatment, start of another anti-cancer therapy, death, withdrawal of informed consent, or for up to 6 months (if in accordance with local laws and regulations) of treatment for an individual participant after sotorasib received marketing authorization approval for the treatment of NSCLC in the participant's country, whichever occurred first. Participants with previously treated locally advanced unresectable/metastatic NSCLC with KRAS p.G12C mutation who were not eligible or did not have the opportunity to enroll in an ongoing sotorasib interventional clinical study and who met the eligibility criteria outlined in the protocol were considered for participation in this study. | ||
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End point title |
Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) [1] | ||||||
End point description |
TEAEs were events categorized as Adverse Events (AEs) starting on or after first dose of investigation product. An AE was defined is any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment.
The full analysis set (FAS) included all enrolled subjects who received at least 1 dose of sotorasib.
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End point type |
Primary
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End point timeframe |
Up to approximately 1 year
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this primary endpoint. |
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Participants Who Experienced a TEAE of Interest [2] | ||||||
End point description |
TEAEs of interest included hepatotoxicity, pneumonitis, and renal toxicity.
The FAS included all enrolled subjects who received at least 1 dose of sotorasib.
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End point type |
Primary
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End point timeframe |
Up to approximately 1 year
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this primary endpoint. |
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Participants Who Experienced a Treatment-related Treatment-emergent AE [3] | ||||||
End point description |
Treatment-related adverse events are treatment-emergent adverse events considered related to investigational product by the investigator.
The FAS included all enrolled subjects who received at least 1 dose of sotorasib.
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End point type |
Primary
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End point timeframe |
Up to approximately 1 year
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this primary endpoint. |
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Participants Who Experienced a Serious TEAE [4] | ||||||
End point description |
A serious adverse event is defined as any untoward medical occurrence that, meets at least 1 of the following serious criteria: results in death, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or other medically important serious event.
The FAS included all enrolled subjects who received at least 1 dose of sotorasib.
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End point type |
Primary
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End point timeframe |
Up to approximately 1 year
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this primary endpoint. |
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Participants Who Experienced a TEAE Leading to Discontinuation of Sotorasib [5] | ||||||
End point description |
The FAS included all enrolled subjects who received at least 1 dose of sotorasib.
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End point type |
Primary
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End point timeframe |
Up to approximately 1 year
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this primary endpoint. |
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| No statistical analyses for this end point | |||||||
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End point title |
Number of participants with each KRAS p.G12C Testing Modality | ||||||||||||||||
End point description |
KRAS p.G12C testing modalities used: next-generation sequencing, polymerase chain reaction, sanger sequencing, other.
The FAS included all enrolled subjects who received at least 1 dose of sotorasib.
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End point type |
Secondary
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End point timeframe |
Screening (up to 28 days)
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Duration of Treatment of Sotorasib | ||||||||
End point description |
The FAS included all enrolled subjects who received at least 1 dose of sotorasib.
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End point type |
Secondary
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End point timeframe |
Up to a maximum of 11.1 months
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Up to approximately 1 year
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Adverse event reporting additional description |
Adverse events were reported for the full analysis set, which included all enrolled subjects who received at least 1 dose of sotorasib (118 participants)
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
25.0
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Reporting groups
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Reporting group title |
Sotorasib
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Reporting group description |
Participants received sotorasib 960 mg orally once daily (QD). Treatment cycles were 28 days long, with no treatment-free intervals. Participants were treated with sotorasib until disease progression, intolerance of protocol treatment, start of another anti-cancer therapy, death, withdrawal of informed consent, or for up to 6 months (if in accordance with local laws and regulations) of treatment for an individual participant after sotorasib received marketing authorization approval for the treatment of NSCLC in the participant's country, whichever occurred first. Participants with previously treated locally advanced unresectable/metastatic NSCLC with KRAS p.G12C mutation who were not eligible or did not have the opportunity to enroll in an ongoing sotorasib interventional clinical study and who met the eligibility criteria outlined in the protocol were considered for participation in this study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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08 Feb 2021 |
The protocol was amended for the following reasons: • Removed microscopic examination from the urinalysis
• Added language to address the risks/benefits assessment for COVID-19
• Added anti-programmed death-1 (PD-1)/anti-PD-1 ligand 1 (PD-L1) immunotherapy and docetaxel to inclusion criteria
• Changed inclusion criteria for estimated glomerular filtration rate to ≥ 45 mL/min/1.73 m^2
• Removed dose modification guidelines for grade ≥ 3 thrombocytopenia, febrile neutropenia, and neutropenia lasting longer than 7 days, and grade 4 hemoglobin decrease |
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06 May 2021 |
The protocol was amended for the following reasons: • Added other anticancer therapies to schedule of activities to be collected at screening and safety follow-up visits
• Added probability and adverse event rate to sample size determination section |
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11 Jan 2022 |
The protocol was amended for the following reasons: • Added interstitial lung disease/pneumonitis as key risk as determined by Amgen and for consistency with other studies within the sotorasib program
• Added sotorasib dose modification guidelines for ILD/pneumonitis
• Added details for reporting of serious adverse events after end of study
• Added requirement for polymerase chain reaction for hepatitis C virus (HCV) ribonucleic acid (RNA) to confirm diagnosis if hepatitis C test positive
• Clarified the definition of participant enrollment: when participant received first dose of sotorasib |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
