Clinical trial • Phase III • Oncology
SUB197397 for Non-small cell lung cancer (KRAS G12C-positive) | Advanced or metastatic non-small cell lung cancer
Phase III trial of SUB197397 for Non-small cell lung cancer (KRAS G12C-positive) | Advanced or metastatic non-small cell lung cancer.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Non-small cell lung cancer (KRAS G12C-positive) | Advanced or metastatic non-small cell lung cancer
- Trial Stage
- Phase III
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 02-05-2024
- First CTIS Authorization Date
- 19-08-2024
Trial design
Randomised, open-label, divarasib versus sotorasib or adagrasib (no dose or schedule specified in the available documentation)-controlled Phase III trial in Sweden, Finland, Poland and others.
- Randomised
- Yes
- Open Label
- Yes
- Comparator
- Divarasib versus sotorasib or adagrasib (no dose or schedule specified in the available documentation)
- Biomarker Stratified
- True, KRAS G12C mutation (strata not specified)
- Target Sample Size
- 78
Eligibility
Recruits 78 Vulnerable population selected. Trial documentation includes dedicated consent forms and appendices for pregnant partners and infant health data (e.g., documents titled 'Consent for Infant Health Data', 'Consent for pregnant partner', 'Consent for Infant Health', and infant-specific ICF appendices). Multiple ICFs (main ICF, pre-screening ICF, optional biopsy, long-term storage, treatment beyond progression) and language variants are provided. These documents indicate specific consent procedures for collecting infant health information and for pregnant partners; parental/guardian consent is required for infant data as set out in the ICFs. No explicit mention of assent procedures for minors is provided in the available material..
- Pregnancy Exclusion
- Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 7 days after the final dose of sotorasib, or of the final dose of adagrasib or divarasib. Female participants of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study treatment.
- Vulnerable Population
- Vulnerable population selected. Trial documentation includes dedicated consent forms and appendices for pregnant partners and infant health data (e.g., documents titled 'Consent for Infant Health Data', 'Consent for pregnant partner', 'Consent for Infant Health', and infant-specific ICF appendices). Multiple ICFs (main ICF, pre-screening ICF, optional biopsy, long-term storage, treatment beyond progression) and language variants are provided. These documents indicate specific consent procedures for collecting infant health information and for pregnant partners; parental/guardian consent is required for infant data as set out in the ICFs. No explicit mention of assent procedures for minors is provided in the available material.
Inclusion criteria
- {"criterion_text":"- Measurable disease according to RECIST v1.1\n- Documentation of the presence of a KRAS G12C mutation through central laboratory testing of a tumor tissue sample or preexisting test results of a blood or tumor tissue sample\n- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1\n- Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or 10-15 (15 preferred) unstained, freshly cut, serial slides with an associated pathology report\n- Negative HIV test, Negative hepatitis B surface antigen (HbsAg) test and Negative hepatitis C virus (HCV) antibody test at screening\n- Adequate hematologic and organ function within 14 days prior to initiation of study treatment"}
Exclusion criteria
- {"criterion_text":"- Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 7 days after the final dose of sotorasib, or of the final dose of adagrasib or divarasib. Female participants of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study treatment.\n- Known hypersensitivity to any of the components of divarasib, or sotorasib or adagrasib\n- Malabsorption syndrome or other condition that would interfere with enteral absorption\n- Known concomitant second oncogenic driver\n- Mixed small-cell lung cancer or large cell neuroendocrine histology\n- Known and untreated, or active CNS metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control)"}
Endpoints
Primary endpoints
- {"endpoint_text":"- 1. Progression-free survival (PFS)","definition_or_measurement_approach":""}
Secondary endpoints
- {"endpoint_text":"- 1. Overall survival (OS)","definition_or_measurement_approach":""}
- {"endpoint_text":"- 2. Confirmed Objective response","definition_or_measurement_approach":""}
- {"endpoint_text":"- 3. Time to confirmed deterioration (TTCD) on the EORTC QLQ-C30 dyspnea item and the physical functioning scale, and the cough scale of the QLQ-LC13 scales","definition_or_measurement_approach":"Measured using EORTC QLQ-C30 dyspnea item and physical functioning scale and QLQ-LC13 cough scale (TTCD)"}
- {"endpoint_text":"- 4. Duration of response (DOR)","definition_or_measurement_approach":""}
- {"endpoint_text":"- 5. Incidence and severity of adverse events, with severity determined according to the NCI CTCAE v5.0 grading scale","definition_or_measurement_approach":"Severity determined according to the NCI CTCAE v5.0 grading scale"}
- {"endpoint_text":"- 6. Change from baseline in selected vital signs and ECG parameters","definition_or_measurement_approach":"Change from baseline in selected vital signs and ECG parameters"}
- {"endpoint_text":"- 7. Change from baseline in selected clinical laboratory test results","definition_or_measurement_approach":"Change from baseline in selected clinical laboratory test results"}
- {"endpoint_text":"- 8. Presence, frequency of occurrence, severity, and/or degree of interference with daily function of symptomatic treatment toxicities (diarrhea, nausea, vomiting, anorexia, alopecia, dyspnea, cough, constipation, myalgia, headache, and rash/acne) as assessed through use of the NCI PRO-CTCAE","definition_or_measurement_approach":"Assessed using the NCI PRO-CTCAE (patient-reported outcomes)"}
- {"endpoint_text":"- 9. Change from baseline in diarrhea, nausea, vomiting, anorexia, alopecia, dyspnea, cough, constipation, myalgia, headache, and rash/acne as assessed through use of the NCI PRO-CTCAE","definition_or_measurement_approach":"Assessed using NCI PRO-CTCAE; change from baseline"}
- {"endpoint_text":"- 10. Frequency of participants’ response of the degree they are troubled with treatment symptoms, as assessed through use of the single-item EORTC Item List (IL46)","definition_or_measurement_approach":"Assessed using the single-item EORTC Item List (IL46)"}
- {"endpoint_text":"- 11. Change from baseline in cough, chest pain, dyspnea, physical and role functioning, and GHS/QoL at each timepoint as assessed through use of the EORTC QLQ-LC13 and QLQ-C30","definition_or_measurement_approach":"Assessed using EORTC QLQ-LC13 and QLQ-C30; change from baseline at each timepoint"}
- {"endpoint_text":"- 12. TTCD on the EORTC QLQ-C30 role functioning and GHS/QoL scales and TTCD on the chest pain scale of the QLQ-LC13 scales","definition_or_measurement_approach":"Measured using EORTC QLQ-C30 role functioning and GHS/QoL scales and QLQ-LC13 chest pain scale (TTCD)"}
Recruitment
- Digital Remote Recruitment
- True, social media posts and digital recruitment materials are included (e.g., 'Social Media Post_V1'); other digital materials/templates referenced in recruitment documents
- Planned Sample Size
- 78
- Recruitment Window Months
- 48
- Consent Approach
- Informed consent is handled via a main Informed Consent Form (ICF) and multiple ICF appendices (pre-screening ICF, optional biopsy, data privacy, infant health, pregnant partner, treatment continuation after progression, etc.). Multiple language versions of the ICF and participant information sheets are provided (English, German, French, Spanish, Italian, Portuguese, Dutch, Greek, Polish, Swedish and country-specific variants). Specific consent forms exist for pregnant partners and for collection of infant health data, indicating parental/guardian consent procedures for infant-related data; pre-screening and mobile nursing consent forms are also provided. The ICF materials indicate consent is obtained from the participant (and from parent/guardian where infant data is collected). No explicit assent procedure for minors is described in the available documents.
Methods
- Templates for communication to doctors / referral from clinicians (document: 'K2_Recruitment material_Template Communication to Doctors')
- Social media posts (document: 'Social Media Post_V1')
- Country-specific recruitment arrangements (K1 documents listed per country)
- Diversity and inclusion recruitment leaflet (document: 'K2_Recruitment material_Diversity_inclusion leaflet')
Geography
- Total Number Of Sites
- 106
- Total Number Of Participants
- 250
Sweden
- Earliest CTIS Part Ii Submission Date
- 23-07-2024
- Latest Decision Or Authorization Date
- 08-09-2025
- Processing Time Days
- 412
- Number Of Sites
- 2
- Number Of Participants
- 4
Sites
- Site Name
- Region Gaevleborg
- Department Name
- Gävle Sjukhus, Lungenheten
- Contact Person Name
- Johan Isaksson
- Contact Person Email
- johan.isaksson@regiongavleborg.se
- Site Name
- Uppsala University Hospital
- Department Name
- Lungmedicin och allergisjukdomar
- Contact Person Name
- Jens Ellingsen
- Contact Person Email
- jens.ellingsen@akademiska.se
Finland
- Earliest CTIS Part Ii Submission Date
- 19-07-2024
- Latest Decision Or Authorization Date
- 04-03-2026
- Processing Time Days
- 593
- Number Of Sites
- 3
- Number Of Participants
- 4
Sites
- Site Name
- HUS-Yhtymae
- Department Name
- Clinical trial Unit
- Contact Person Name
- Katriina Jalkanen
- Contact Person Email
- katriina.jalkanen@hus.fi
- Site Name
- Turku University Hospital
- Department Name
- Pulmonogy
- Contact Person Name
- Maria Silvoniemi
- Contact Person Email
- maria.silvoniemi@varha.fi
- Site Name
- Pohjois-Savon hyvinvointialue
- Department Name
- Oncology
- Contact Person Name
- Okko-Sakari Kääriäinen
- Contact Person Email
- okko.kaariainen@pshyvinvointialue.fi
Poland
- Earliest CTIS Part Ii Submission Date
- 16-05-2024
- Latest Decision Or Authorization Date
- 26-02-2026
- Processing Time Days
- 649
- Number Of Sites
- 11
- Number Of Participants
- 30
Greece
- Earliest CTIS Part Ii Submission Date
- 16-05-2024
- Latest Decision Or Authorization Date
- 12-02-2026
- Processing Time Days
- 637
- Number Of Sites
- 6
- Number Of Participants
- 20
Austria
- Earliest CTIS Part Ii Submission Date
- 16-05-2024
- Latest Decision Or Authorization Date
- 16-02-2026
- Processing Time Days
- 641
- Number Of Sites
- 1
- Number Of Participants
- 11
Netherlands
- Earliest CTIS Part Ii Submission Date
- 25-07-2024
- Latest Decision Or Authorization Date
- 13-02-2026
- Processing Time Days
- 568
- Number Of Sites
- 7
- Number Of Participants
- 20
Belgium
- Earliest CTIS Part Ii Submission Date
- 22-07-2024
- Latest Decision Or Authorization Date
- 04-03-2026
- Processing Time Days
- 590
- Number Of Sites
- 11
- Number Of Participants
- 24
Italy
- Earliest CTIS Part Ii Submission Date
- 17-07-2024
- Latest Decision Or Authorization Date
- 17-02-2026
- Processing Time Days
- 580
- Number Of Sites
- 18
- Number Of Participants
- 34
Portugal
- Earliest CTIS Part Ii Submission Date
- 24-07-2024
- Latest Decision Or Authorization Date
- 13-02-2026
- Processing Time Days
- 569
- Number Of Sites
- 5
- Number Of Participants
- 12
Germany
- Earliest CTIS Part Ii Submission Date
- 22-07-2024
- Latest Decision Or Authorization Date
- 13-02-2026
- Processing Time Days
- 571
- Number Of Sites
- 18
- Number Of Participants
- 30
France
- Earliest CTIS Part Ii Submission Date
- 22-07-2024
- Latest Decision Or Authorization Date
- 22-02-2026
- Processing Time Days
- 580
- Number Of Sites
- 13
- Number Of Participants
- 33
Spain
- Earliest CTIS Part Ii Submission Date
- 08-07-2024
- Latest Decision Or Authorization Date
- 16-03-2026
- Processing Time Days
- 616
- Number Of Sites
- 8
- Number Of Participants
- 22
Denmark
- Earliest CTIS Part Ii Submission Date
- 22-07-2024
- Latest Decision Or Authorization Date
- 26-03-2026
- Processing Time Days
- 612
- Number Of Sites
- 3
- Number Of Participants
- 6
Sponsor
Primary sponsor
- Full Name
- F. Hoffmann-La Roche AG
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Switzerland
Contract research organisations
- Name
- IQVIA Limited
- Responsibilities
- Monitoring
- Name
- Syneos Health, LLC
- Responsibilities
- code: 6
- Name
- Almac Clinical Technologies LLC
- Responsibilities
- code: 3
- Name
- Labcorp Central Laboratory Services (entities)
- Responsibilities
- Central laboratory services (codes: 4)
- Name
- Covance Central Laboratory Services Inc.
- Responsibilities
- code: 4
Third parties
- {"country":"France","full_name":"Median Technologies","duties_or_roles":"Imaging Vendor","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Cellcarta Naperville LLC","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
- {"country":"France","full_name":"Kayentis","duties_or_roles":"e-PRO","organisation_type":"Non-Pharmaceutical company"}
- {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"code: 4","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Foundation Medicine, Inc.","duties_or_roles":"code: 4","organisation_type":"Industry"}
- {"country":"Germany","full_name":"Foundation Medicine GmbH","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
- {"country":"Singapore","full_name":"Labcorp Development (Asia) Pte Ltd","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"code: 3","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Covance Central Laboratory Services Inc.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
- {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Monitoring","organisation_type":"Pharmaceutical company"}
- {"country":"India","full_name":"Syneos Health, LLC","duties_or_roles":"code: 6","organisation_type":"Industry"}
Investigational products
- Investigational Product Name
- Divarasib
- Modality
- Small molecule
- Investigational Product Name
- Sotorasib (AMG 510)
- Active Substance
- SUB197397
- Modality
- Small molecule
- Authorisation Status
- Marketing authorisation EU number(s) present (e.g., EU/1/21/1603/001 / related PRD9412069 entries)
- Investigational Product Name
- Adagrasib (MRTX-849)
- Active Substance
- SUB218270
- Modality
- Small molecule
- Authorisation Status
- Marketing authorisation EU number(s) present for Mirati products (e.g., EU/1/23/1744/001 / PRD11075055 / PRD11078995 entries)
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