SOTORASIB for Non-small cell lung cancer | Colorectal cancer | Advanced solid tumour (KRAS p.G12C mutant)

Inclusion criteria

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

Exclusion criteria

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

Primary endpoints

• {"endpoint_text":"- Phase 1 Part 1a and Part 2a Monotherapy Cohorts: Incidence of treatment emergent adverse events, treatment-related adverse events, and clinically significant changes in vital signs, physical examinations, electrocardiograms (ECGs), and clinical laboratory tests","definition_or_measurement_approach":"Incidence measured via clinical AE reporting, vital sign measurements, physical examinations, ECGs and clinical laboratory tests as recorded in study assessments."}
• {"endpoint_text":"- Phase 1 Part 1a and Part 2a Monotherapy Cohorts: Incidence of dose-limiting toxicity (DLT)","definition_or_measurement_approach":"DLTs identified per protocol-defined toxicity criteria during DLT evaluation window (protocol-defined)."}
• {"endpoint_text":"- Phase 1 Part 1b and Part 2b Monotherapy Cohorts and Phase 1 Part 1d and Part 2d Monotherapy Cohorts: Incidence of DLTs, treatment emergent adverse events, treatment-related adverse events, and changes in vital signs, ECGs, and clinical laboratory tests","definition_or_measurement_approach":"Incidence measured via clinical AE reporting, DLT assessment, vitals, ECGs and laboratory evaluations per protocol."}
• {"endpoint_text":"- Phase 1 Part 1c and Part 2c Pembrolizumab Combination Therapy Cohorts: Incidence of DLTs, treatment emergent adverse events, treatment-related adverse events, and clinically significant changes in vital signs, physical examinations, ECGs, and clinical laboratory tests","definition_or_measurement_approach":"Safety events and DLTs assessed and recorded per protocol using clinical assessments, ECGs and labs."}
• {"endpoint_text":"- Phase 1 Part 2e Previously Untreated Metastatic NSCLC Monotherapy Cohort: Incidence of DLTs, treatment emergent adverse events, treatment-related adverse events, and changes in vital signs, ECGs, and clinical laboratory tests","definition_or_measurement_approach":"Safety endpoints captured via AE reporting, vital signs, ECGs and laboratory tests according to protocol-defined schedules."}
• {"endpoint_text":"- Phase 1 Part 2e Previously Untreated Metastatic NSCLC Monotherapy Cohort: Objective response (OR = complete response [CR] + partial response [PR]), duration of response (DOR), disease control (CR + PR + stable disease [SD]), duration of SD, and time to response measured by CT or MRI and assessed per RECIST 1.1. Response will be assessed by BICR. CR and PR require confirmatory CT or MRI repeat assessment at least 4 weeks after the first detection of response.","definition_or_measurement_approach":"Tumour responses measured by CT or MRI and assessed per RECIST 1.1 by blinded independent central review (BICR); CR/PR require confirmatory imaging ≥4 weeks after first detection."}
• {"endpoint_text":"- Phase 2 Part A – NSCLC, CRC, and other tumor types (AMG 510 monotherapy): Objective response (OR = CR + PR), measured by CT or MRI and assessed per RECIST 1.1. Response will be assessed by BICR. Complete response and PR require confirmatory CT or MRI repeat assessment at least 4 weeks after the first detection of response.","definition_or_measurement_approach":"Tumour responses measured by CT or MRI and evaluated per RECIST 1.1 by BICR; confirmatory imaging required for CR/PR ≥4 weeks after initial detection."}
• {"endpoint_text":"- Phase 2 Part B – NSCLC (Dose Comparison Study): Objective response (ORR = CR + PR), measured by CT or MRI and assessed per RECIST 1.1. Response will be assessed by BICR. Complete response and PR require confirmatory CT or MRI repeat assessment at least 4 weeks after the first detection of response.","definition_or_measurement_approach":"Tumour responses measured via CT/MRI and assessed per RECIST 1.1 by BICR; CR/PR confirmation required ≥4 weeks after first detection."}
• {"endpoint_text":"- Phase 2 Part B – NSCLC (Dose Comparison Study): Treatment emergent adverse events (TEAE), grade greater/equal to 3 TEAE, serious adverse event (SAEs), and events of interest (EOIs)","definition_or_measurement_approach":"Safety endpoints captured as TEAEs graded by CTCAE, SAEs and protocol-defined events of interest recorded throughout study."}

Secondary endpoints

• {"endpoint_text":"- Phase 1 Part 1a and Part 2a Monotherapy Cohorts (QD), Phase 1 Part 1b and Part 2b Monotherapy Cohorts (BID), and Phase 1 Part 1d and Part 2d Monotherapy Cohorts (QD): PK parameters of AMG 510 including, but not limited to, maximum plasma concentration (Cmax), time to achieve Cmax (tmax), and area under the plasma concentration-time curve (AUC)","definition_or_measurement_approach":"PK parameters (Cmax, tmax, AUC, etc.) measured from plasma concentration-time sampling per protocol."}
• {"endpoint_text":"- Phase 1 Part 1a and Part 2a Monotherapy Cohorts (QD), Phase 1 Part 1b and Part 2b Monotherapy Cohorts (BID), and Phase 1 Part 1d and Part 2d Monotherapy Cohorts (QD): OR, DOR, disease control, progression free survival (PFS), duration of stable disease, and TTR measured by CT or MRI and assessed per RECIST 1.1. Response will be assessed by BICR. Complete response and PR require confirmatory CT or MRI repeat assessment at least 4 weeks after the first detection of response.","definition_or_measurement_approach":"Efficacy outcomes measured by CT/MRI per RECIST 1.1 and adjudicated by BICR; CR/PR confirmation required ≥4 weeks."}
• {"endpoint_text":"- Phase 1 Part 1a and Part 2a Monotherapy Cohorts (QD), Phase 1 Part 1b and Part 2b Monotherapy Cohorts (BID), and Phase 1 Part 1d and Part 2d Monotherapy Cohorts (QD): Overall survival (OS)","definition_or_measurement_approach":"OS measured as time from first dose to death from any cause."}
• {"endpoint_text":"- Phase 1 Part 1a and Part 2a Monotherapy Cohorts (QD), Phase 1 Part 1b and Part 2b Monotherapy Cohorts (BID), and Phase 1 Part 1d and Part 2d Monotherapy Cohorts (QD): PK parameters of AMG 510 including, but not limited to, Cmax, tmax, and AUC in the fed and/or fasted state","definition_or_measurement_approach":"PK comparisons in fed vs fasted state using plasma concentration-time analysis (Cmax, tmax, AUC)."}
• {"endpoint_text":"- Phase 1 Part 1a and Part 2a Monotherapy Cohorts (QD), Phase 1 Part 1b and Part 2b Monotherapy Cohorts (BID), and Phase 1 Part 1d and Part 2d Monotherapy Cohorts (QD): AMG 510 exposure/QTc interval relationship","definition_or_measurement_approach":"Exposure–QTc relationship evaluated using PK (exposure) and ECG-derived QTc interval measurements per protocol."}
• {"endpoint_text":"- Phase 1 Part 1c and Part 2c Pembrolizumab Combination Therapy Cohorts: PK parameters of AMG 510 including, but not limited to, Cmax, tmax, and AUC","definition_or_measurement_approach":"PK parameters measured for AMG 510 when administered with pembrolizumab (Cmax, tmax, AUC)."}
• {"endpoint_text":"- Phase 1 Part 1c and Part 2c Pembrolizumab Combination Therapy Cohorts: OR, DOR, disease control, PFS, duration of stable disease, and TTR measured by CT or MRI and assessed per RECIST 1.1. Response will be assessed by BICR. Complete response and PR require confirmatory CT or MRI repeat assessment at least 4 weeks after the first detection of response.","definition_or_measurement_approach":"Tumour response endpoints measured by CT/MRI per RECIST 1.1 and assessed by BICR; confirmatory imaging for CR/PR required."}
• {"endpoint_text":"- Phase 1 Part 1c and Part 2c Pembrolizumab Combination Therapy Cohorts: OS","definition_or_measurement_approach":"Overall survival measured from first dose to death from any cause."}
• {"endpoint_text":"- Phase 1 Part 2e Previously Untreated Metastatic NSCLC Monotherapy Cohort: PK parameters of AMG 510 including, but not limited to Cmax, tmax, and AUC","definition_or_measurement_approach":"PK sampling for AMG 510 (Cmax, tmax, AUC) per protocol schedule."}
• {"endpoint_text":"- Phase 1 Part 2e Previously Untreated Metastatic NSCLC Monotherapy Cohort: PK parameters for midazolam including, but not limited to: Cmax, AUC, clearance, and t1/2","definition_or_measurement_approach":"Midazolam PK parameters measured in substudy when administered with and without AMG 510 (Cmax, AUC, clearance, t1/2)."}
• {"endpoint_text":"- Phase 1 Part 2e Previously Untreated Metastatic NSCLC Monotherapy Cohort: - OS - PFS","definition_or_measurement_approach":"OS and PFS measured per standard time-to-event definitions (time from first dose to death or progression/death respectively)."}
• {"endpoint_text":"- Phase 2 Part A – NSCLC, CRC, and other tumor types (AMG 510 monotherapy): - Duration of response (DOR) - Disease control - Time to response (TTR) - Progression-free survival (PFS) - Overall survival (OS) - 6-month PFS and 12 month PFS - 12 month OS","definition_or_measurement_approach":"Tumour efficacy endpoints measured by imaging per RECIST 1.1 and time-to-event analysis (PFS, OS); DOR and TTR per RECIST assessments."}
• {"endpoint_text":"- Phase 2 Part A – NSCLC, CRC, and other tumor types (AMG 510 monotherapy): Incidence and severity of adverse events","definition_or_measurement_approach":"Safety assessed by AE reporting and CTCAE grading."}
• {"endpoint_text":"- Phase 2 Part A – NSCLC, CRC, and other tumor types (AMG 510 monotherapy): PK parameters of AMG 510 including, but not limited to, Cmax, tmax, and AUC","definition_or_measurement_approach":"PK measurements (Cmax, tmax, AUC) per protocol sampling."}
• {"endpoint_text":"- Phase 2 Part B – NSCLC (Dose Comparison Study): - Duration of response (DOR) - Disease control (DCR = CR + PR + SD) - Depth of response (best percent change from baseline in lesion sum diameters) - Time to response (TTR) - Progression free survival (PFS) - Overall survival (OS)","definition_or_measurement_approach":"Efficacy determined by RECIST 1.1 imaging assessments (CT/MRI) and time-to-event analyses; depth of response as percent change in sum diameters."}
• {"endpoint_text":"- Phase 2 Part B – NSCLC (Dose Comparison Study): PK parameters of AMG 510 including, but not limited to, Cmax and AUC","definition_or_measurement_approach":"PK sampling for specified doses (Cmax, AUC) per protocol."}
• {"endpoint_text":"- Phase 2 Part B – NSCLC: Changes in cancer-specific symptoms and overall health status using subject reported outcome instruments: Impact of treatment on disease related symptoms and HRQOL (instruments; EORTC QLQ C30 + disease-specific modules QLQ LC13 and NSCLC SAQ for NSCLC; PGIS and PGIC in cough, dyspnea and chest pain among NSCLC subjects). (cont.)","definition_or_measurement_approach":"Patient-reported outcomes collected using EORTC QLQ-C30 and disease-specific modules, PGIS/PGIC and NSCLC-specific instruments to assess symptoms and HRQOL."}
• {"endpoint_text":"- Phase 2 Part B – NSCLC: (cont. from prev. point) Treatment-related symptoms and impact on the subject (EORTC QLQ C30, selected questions from the PRO-CTCAE library and a single item about symptom bother, item GP5 of the FACT-G).","definition_or_measurement_approach":"Treatment-related symptom burden assessed via EORTC QLQ-C30, selected PRO-CTCAE items and FACT-G item GP5."}
• {"endpoint_text":"- Phase 2 Part B – NSCLC (Dose Comparison Study): Physical function (instrument: EORTC QLQ-C30, Physical function scale)","definition_or_measurement_approach":"Physical function assessed by the EORTC QLQ-C30 physical function scale (patient-reported)."}

Hungary

Earliest CTIS Part Ii Submission Date

11-03-2024

Latest Decision Or Authorization Date

19-04-2024

Processing Time Days

39

Number Of Sites

1

Number Of Participants

16

Portugal

Earliest CTIS Part Ii Submission Date

11-03-2024

Latest Decision Or Authorization Date

18-04-2024

Processing Time Days

38

Number Of Sites

1

Number Of Participants

9

Spain

Earliest CTIS Part Ii Submission Date

11-03-2024

Latest Decision Or Authorization Date

22-04-2024

Processing Time Days

42

Number Of Sites

2

Number Of Participants

27

France

Earliest CTIS Part Ii Submission Date

11-03-2024

Latest Decision Or Authorization Date

23-04-2024

Processing Time Days

43

Number Of Sites

1

Number Of Participants

40

Romania

Earliest CTIS Part Ii Submission Date

11-03-2024

Latest Decision Or Authorization Date

23-04-2024

Processing Time Days

43

Number Of Sites

1

Number Of Participants

10

Belgium

Earliest CTIS Part Ii Submission Date

11-03-2024

Latest Decision Or Authorization Date

19-04-2024

Processing Time Days

39

Number Of Sites

3

Number Of Participants

88

Greece

Earliest CTIS Part Ii Submission Date

10-06-2024

Latest Decision Or Authorization Date

17-06-2024

Processing Time Days

7

Number Of Sites

2

Number Of Participants

20

Austria

Earliest CTIS Part Ii Submission Date

11-03-2024

Latest Decision Or Authorization Date

23-04-2024

Processing Time Days

43

Number Of Sites

4

Number Of Participants

36

Primary sponsor

Full Name

Amgen Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Excelya Greece CRO Single Member S.A.

Responsibilities

Operational sponsor duties (sponsor duty code '1')

Name

Iqvia Rds Inc.

Responsibilities

IVRS - treatment randomisation and other operational roles (codes 1, 6 and IVRS)

Name

Almac Clinical Technologies LLC

Responsibilities

Sponsor duty code '3' (as listed)

Third parties

• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"ECG analysis/ review","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"Excelya Greece CRO Single Member S.A.","duties_or_roles":"code 1 (sponsor duty code listed as '1')","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Rad Md LLC","duties_or_roles":"Independent Imaging Review","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Neogenomics Laboratories Inc.","duties_or_roles":"Histopathology","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"Patient-reported outcomes (PRO) questionnaires and eDiary.","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"code 3 (sponsor duty code listed as '3')","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Iqvia Rds Inc.","duties_or_roles":"IVRS - treatment randomisation; other duties (codes 1 and 6 also listed)","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Laboratory services (sponsor duty code '4')","organisation_type":"Pharmaceutical company"}