KRAS p.G12C mutant untreated stage IV Non-Small Cell Lung Cancer (NSCLC) MedDRA version: 21.1 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Sotorasib
Product Code: AMG 510
Pharmaceutical Form: Tablet
INN or Proposed INN: Sotorasib
Current Sponsor code: AMG 510
Other descriptive name: AMG 510
Concentration unit: mg milligram(
Sponsors
Amgen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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 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 =65 years) yes F.1.3.1 Number of subjects for this age range 70
Exclusion criteria
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 unwillin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - 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.;Secondary Objective: - 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;Primary 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);Timepoint(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. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary 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).;Timepoint(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. | — |
Countries
Belgium, Denmark, France, Germany, Italy, Netherlands, Spain, Sweden, Switzerland, Turkey, United States
Contacts
Public ContactIHQ medical Info-Clinical Trials
Amgen S.A.
Outcome results
None listed