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    The EU Clinical Trials Register currently displays   43873   clinical trials with a EudraCT protocol, of which   7292   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2021-002638-18
    Sponsor's Protocol Code Number:20190288
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-06-30
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedFrance - ANSM
    A.2EudraCT number2021-002638-18
    A.3Full title of the trial
    A Phase 2, Multicenter, Open-label Study of Sotorasib (AMG 510) in Subjects with Stage IV NSCLC Whose Tumors Harbor a KRASG12C Mutation in Need of First-line Treatment
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Clinical study to investigate the safety, efficacy and pharmacokinetics of sotorasib in Subjects with Non-Small Cell Lung Cancer
    A.3.2Name or abbreviated title of the trial where available
    CodeBreaK 201
    A.4.1Sponsor's protocol code number20190288
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAmgen Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAmgen Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAmgen SAS
    B.5.2Functional name of contact pointMedical Information
    B.5.3 Address:
    B.5.3.1Street Address18-20 Quai du point du jour
    B.5.3.2Town/ cityBoulogne-Billancourt
    B.5.3.3Post code92100
    B.5.3.4CountryFrance
    B.5.4Telephone number0969363363
    B.5.6E-mailfr-medinfo@amgen.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameSotorasib
    D.3.2Product code AMG 510
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSotorasib
    D.3.9.2Current sponsor codeAMG 510
    D.3.9.3Other descriptive nameAMG 510
    D.3.9.4EV Substance CodeSUB197397
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number120
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    KRAS p.G12C mutant untreated stage IV Non-Small Cell Lung Cancer (NSCLC)
    E.1.1.1Medical condition in easily understood language
    Non-small cell lung cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10029522
    E.1.2Term Non-small cell lung cancer stage IV
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    - To evaluate the tumor objective response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria in subjects who receive sotorasib at either 960 mg daily (QD) or 240 mg QD 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 subjects with PD L1 < 1% and in a subgroup of subjects with STK11 co mutation.
    E.2.2Secondary objectives of the trial
    - To evaluate other measures of efficacy.
    - To evaluate the safety and tolerability of sotorasib.
    - Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral tablet formulation
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Untreated stage IV (per AJCC v8) NSCLC.
    • Subjects who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed greater than 12 months prior to the development of metastatic disease.
    2. Pathologically documented, metastatic NSCLC with KRAS p.G12C mutation identified through molecular testing. KRAS p.G12C mutation must be performed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory or equivalent.
    3. Subject has provided informed consent prior to initiation of any study specific activities/procedures.
    4. Age ? 18 years.
    5. PD-L1 TPS score < 1% as determined by pharm Dx DAKO 22C3 or Ventana SP263 IHC. If subjects do not have PD-L1 TPS score < 1%, STK11 loss of function mutation as determined by NGS must be present. Subjects with PD-L1 TPS score < 1% may also have presence of STK11 mutation.
    6. Subjects must be willing to provide archived tumor tissue samples (formalin-fixed paraffin-embedded [FFPE] sample collected within 5 years) or willing to undergo pretreatment tumor biopsy.
    7. Subjects must be willing at enrollment to undergo tumor biopsy at disease progression on trial, if feasible.
    8. Measurable disease per RECIST 1.1 criteria. Lesions previously radiated are not considered measurable unless they have progressed after radiation.
    9. Eastern Cooperative Oncology Group (ECOG) Performance Status of ? 1.
    10. Life expectancy of > 3 months, in the opinion of the investigator.
    11. Ability to take oral medications and willing to record daily adherence to investigational product.
    12. Adequate hematological laboratory assessments, defined as the following within 10 days prior to start of study therapy.
    • Absolute neutrophil count (ANC) ? 1500 cells/µL
    • Hemoglobin ? 9.0 g/dL
    • Platelet count ? 75 000/µL
    13. Adequate renal laboratory assessments, defined as the following:
    • Estimated glomerular filtration rate based on Modification of Diet in Renal Disease (MDRD) calculation ? 30 mL/min/1.73 m2
    • Estimated glomerular filtration rate = creatinine assay x serum creatinine-1.154 x age-0.203 x sex (0.742 if female) x race (1.210 if black)
    14. Adequate hepatic laboratory assessments, as follows:
    • Aspartate aminotransferase (AST) ? 2.5 x upper limit of normal (ULN)
    • Alanine aminotransferase (ALT) ? 2.5 x ULN
    • Total bilirubin (TBL) ? 1.5 x ULN for subjects with documented Gilbert’s syndrome or < 3.0 x ULN for subjects for whom the indirect bilirubin level suggests an extrahepatic source of elevation
    15. Adequate coagulation laboratory assessments, as follows:
    • Prothrombin time (PT) or partial thromboplastin time (PTT) < 1.5 x ULN, OR
    • International normalized ratio (INR) < 1.5 x ULN or within target range if on prophylactic anticoagulation therapy
    16. QTc equal or less than 470 msec in females or equal or less than 450 msec in males
    E.4Principal exclusion criteria
    1. Mixed small-cell lung cancer and NSCLC histology.
    2. Subject has received prior treatment for metastatic NSCLC.
    3. History or presence of malignancy unless treated with curative intent and no evidence of disease ? 3 years. [Please refer to the protocol for further detail on the exceptions to this criteria]
    4. Spinal cord compression, untreated or active brain metastases and/or carcinomatous meningitis. Subjects who have had brain metastases resected or have received whole brain radiation therapy ending at least 4 weeks prior to study day 1 are eligible if they meet all of the following criteria. Subjects with untreated brain metastases must also meet these criteria. [please refer to the protocol for further detail of the criteria]
    5. Myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure, unstable angina, or cardiac arrythmia requiring medication.
    6. Gastrointestinal (GI) tract disease causing the inability to take oral medication, malabsorption syndrome, requirement for intravenous (IV) alimentation, uncontrolled inflammatory GI disease.
    7. Evidence of hepatitis infection
    8. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures at a frequency greater than monthly.
    9. Known positive test for human immunodeficiency virus (HIV).
    10. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
    11. Active infection within 2 weeks of study day 1 requiring therapeutic oral or IV antibiotics.
    12. Major surgery within 28 days of study day 1.
    13. Unresolved toxicities from prior anti-tumor therapy.
    14. Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, or investigational agent) within 12 months.
    15. Therapeutic or palliative radiation therapy within 2 weeks of study day 1. Subjects must have recovered from all radiotherapy related toxicity to grade 1 or better.
    16. Received radiation therapy to the lung that is > 30 Gy within 6 months of first dose of trial treatment.
    17. Previous treatment with a covalent KRAS p.G12C inhibitor.
    18. Use of known cytochrome P450 (CYP) 3A4 sensitive substrates or P-gp substrates, with a narrow therapeutic window, within 14 days or 5 half-lives of the drug or its major active metabolite, whichever is longer.
    19. Use of strong inducers of CYP3A4 (including herbal supplements such as St. John's wort) within 14 days or 5 half-lives, whichever is longer.
    20. Use of proton-pump inhibitors (PPIs) or histamine 2 (H2) receptor antagonists (H2RA) within 14 days or 5 half-lives of the drug or its major active metabolite, whichever is longer.
    21. Currently receiving treatment in another investigational device or drug study. Other investigational procedures while participating in this study are excluded.
    22. Female subjects of childbearing potential unwilling to use protocol specified method of contraception during treatment and for an additional 7 days after the last dose of sotorasib
    23. Female subjects who are breastfeeding or who plan to breastfeed while on study through 7 days after the last dose of sotorasib.
    24. Female subjects planning to become pregnant while on study through 7 days after the last dose of sotorasib.
    25. Female subjects of childbearing potential with a positive pregnancy test assessed at Screening or day 1 by a highly sensitive urine or serum pregnancy test.
    26. Male subjects with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional 7 days after the last dose of sotorasib.
    27. Male subjects with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for an additional 7 days after the last dose of sotorasib.
    28. Male subjects unwilling to abstain from donating sperm during treatment and for an additional 7 days after the last dose of sotorasib.
    29. Subject has known sensitivity to any of the products or components to be administered during dosing.
    30. Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures.
    31. Subject unable to receive both iodinated contrast for computed tomography (CT) scans and gadolinium contrast for MRI scans.
    32. History or evidence of any other clinically significant disorder, condition or disease that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.

    For additional details please refer to the study protocol.
    E.5 End points
    E.5.1Primary end point(s)
    Objective response (OR) (OR = complete response [CR] + partial response [PR]), measured by computed tomography (CT) or magnetic resonance imaging (MRI) and assessed per RECIST v1.1 per Blinded Independent Central Review (BICR)
    E.5.1.1Timepoint(s) of evaluation of this end point
    - Safety data will be reviewed on an ongoing basis by Amgen.
    - The primary analysis is planned approximately 6 months after all subjects are enrolled and have had the opportunity to complete at least 1 post-baseline tumor assessment.
    - The futility analysis will occur after approximately 60 subjects across 2 treatment dose arms become response evaluable, defined as received at least 1 dose of sotorasib and had been enrolled for at least 7 weeks.
    - The final analysis will occur when the end of study.
    E.5.2Secondary end point(s)
    • Disease control (CR +PR + stable disease [SD])
    • Duration of response (DOR)
    • Time to response (TTR)
    • Progression-free survival (PFS)
    • Overall survival (OS)
    • Treatment emergent adverse events, treatment-related adverse events, and changes in vital signs, electrocardiogram [ECGs], and clinical laboratory tests.
    • PK parameters of sotorasib including, but not limited to, maximum plasma concentration (Cmax), time to achieve Cmax (tmax), and area under the plasma concentration-time curve (AUC).
    E.5.2.1Timepoint(s) of evaluation of this end point
    - Safety data will be reviewed on an ongoing basis by Amgen.
    - The primary analysis is planned approximately 6 months after all subjects are enrolled and have had the opportunity to complete at least 1 post-baseline tumor assessment.
    - The futility analysis will occur after approximately 60 subjects across 2 treatment dose arms become response evaluable, defined as received at least 1 dose of sotorasib and had been enrolled for at least 7 weeks.
    - The final analysis will occur when the end of study.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA31
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Turkey
    United States
    Switzerland
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of study date is defined as the date when the last subject across all sites is assessed or receives an intervention for evaluation in the study (ie, last subject last visit), including any additional parts in the study (eg, LTFU, additional antibody testing), as applicable.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years6
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 100
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 70
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state25
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 83
    F.4.2.2In the whole clinical trial 170
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-10-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-07-28
    P. End of Trial
    P.End of Trial StatusOngoing
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