Clinical Trial of AMG510 in Stage III Unresectable NSCLC KRAS p.G12C Patients and Ineligible for Chemo-radiotherapy

Korábbi kezelés

• 2. Weight loss >10% within the previous 3 months
• 4. Major surgery within 28 days of study day 1
• 6. Significant cardiovascular disease, such as New York Heart Association cardiac disease (ClassII or greater), myocardial infarction within 6 months prior to study day 1, unstable arrhythmias or unstable angina
• 8. Severe infections within 4 weeks prior to randomization including, but not limited to hospitalization for complications of infection, bacteremia or severe pneumonia
• 9. Therapeutic oral or intravenous antibiotics within 2 weeks prior to randomization
• 10. Patients with any concomitant and uncontrolled medical disorder
• 13. Prior treatment with anti-neoplasic drugs
• 14. Malignancies other than NSCLC within 3 years prior to enrollment
• 16. Positive test for HIV. All patients will be tested for HIV prior to inclusion into the study; patients who test positive for HIV will be excluded from the clinical study.
• 23. Use of strong inducers of CYP3A4 within 14 days of half-lives (whichever is longer) prior to study day 1
• 24. Use of proton pump inhibitors within 14 days to study day

Más betegség

• 5. Significant gastrointestinal disorder that results in significant malabsorption, requirement for intravenous alimentation, or inability to take oral medication
• 7. Ongoing cardiac dysrhythmias of CTCAE grade ≥2, uncontrolled atrial fibrillation of any grade or QTcF interval > 470ms
• 11. Patients with vena cava syndrome
• 12. Malignant pleural or pericardial effusion: both will be considered as suggestive of metastaticdisease. Also, are excluded those with negative cytology but being exudates. Patients with non-visible by thoracic X-ray pleural effusion or too small to be safely punctured could be included.
• 17. Patients with active hepatitis B or hepatitis C.
• 18. Active tuberculosis.
• 20. Patients with illnesses or conditions that interfere with their capacity to understand follow and/or comply with study procedures.
• 21. Known or suspected hypersensitivity to drugs with similar chemical structures to the study drug

Laborértékek

• 1. Patients with a known sensitizing mutation in the epidermal growth factor receptor (EGFR) gene, ALK translocations or ROS1 mutations
• 19. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications.
• 22. Evidence of any other disorder or significant laboratory finding that makes the patient undesirable to participate in the study

Egyéb

• 3. Patients with uncontrolled neuropathy (sensory) grade 2 or greater regardless of cause according to CTCAE v5.0
• 15. Women who are pregnant, lactating, or intending to become pregnant during the study.

• 1. Male or female, aged ≤ 80 years old
• 2. ECOG performance status of 0-1
• 3. Histologically or cytologically confirmed, unresectable Stage III (IIIA-N2, IIIB and IIIC) NSCLC according to 8th version of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology.
• 4. Patients who have documentation of KRAS p.G12C prior to enrollment. This determination can be done either by solid or liquid biopsy.
• 5. No prior treatment for unresectable Stage III (IIIA-N2, IIIB and IIIC) NSCLC.
• 6. Having a life expectancy ≥ 12 weeks
• 7. Patients must be ineligible for concurrent chemo-radiotherapy because of:
  • Tumor size ≥ 5 cm and lymph node N2 involvement
  • The target lesion has to be bulky disease and/or more than 35% of the total volume of the two lungs should receive more than 20 Gy (V20) or inadequate pulmonary function
  • Interstitial Lung diseases
  • Prior treatment with thoracic radiotherapy for any reason
  • Or under decision of a tumor committee as inappropriate due to local characteristics to perform treatment upfront
• 8. PET-CT at baseline is mandatory to confirm the absence of distant disease and to confirm unresectable disease
• 9. PET-CT positive mediastinic adenopathies must be histologically confirmed. Mediastinic involvement could be considered without histological test when no margin can be distinguished in the lymph node mass.
• 10. Brain CT or MRI is mandatory
• 11. Patients with at least 1 measurable lesion, as defined by RECIST v1.1.
• 12. Adequate hematologic and organ function.
• 13. All patients are notified of the investigational nature of this study and signed a written informed consent in accordance with institutional and national guidelines, including the Declaration of Helsinki prior to any trial-related intervention.
• 14. Willingness and ability to comply with scheduled visits and study procedures
• 15. For female patients of childbearing potential, a negative pregnancy test must have been documented prior to enrollment (within 14 days prior to enrollment).
• 16. For female patients of childbearing potential, agreement (by patient and/or partner) to usea highly effective form(s) of contraception that results in a low failure rate (< 1% per year)when used consistently and correctly, and to continue its use for 7 days after the last dose of AMG510 (Sotorasib). No hormonal methods and preferably barrier method always containing a spermicide, intrauterine device (IUD): intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner (on the understanding that this is the only one partner during the whole study duration), and sexual abstinence.
• 17. For male patients with female partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception that results in a low failure rate [< 1% per year] when used consistently and correctly, and to continue its use for 7 days after the last dose of AMG510 (Sotorasib).
• 18. Women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to enrollment.
• 19. QTc interval must be ≤ 470 msec in females and ≤ 450 msec in males, based on the average obtained from three ECG.