Clinical study to investigate the safety, efficacy and pharmacokinetics of sotorasib in Subjects with Non-Small Cell Lung Cancer
- Conditions
- KRAS p.G12C mutant untreated stage IV Non-Small Cell Lung Cancer (NSCLC)MedDRA version: 21.1Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-002638-18-NL
- Lead Sponsor
- Amgen Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 170
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.
8. Measurable disease per investigator interpretation using 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
• 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70
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, 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. [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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method