A research study to evaluate the activity of Sotorasib for the treatment of patients with non-operable non-small cell lung cancer with a KRAS mutation and not eligible for chemotherapy treatment

Phase 1

Conditions: nresectable stage III (IIIA-N2, IIIB, IIIC) KRAS p.G12C non-small cell lung cancer
MedDRA version: 21.1Level: PTClassification code 10029519Term: Non-small cell lung cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2021-004576-34-ES

Lead Sponsor: Fundación GECP

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 43

Inclusion Criteria

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:
a. Tumor size = 5 cm and lymph node N2 involvement
b. 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
c. Interstitial Lung diseases
d. Prior treatment with thoracic radiotherapy for any reason
e. 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 defined by the following laboratory results obtained within 14 days prior to enrollment:
• Absolute neutrophil count (ANC) Neutrophils = 1500 cells/µL (without granulocyte colony-stimulating factor support within 10 days of laboratory test used to determine eligibility)
• Lymphocyte count = 500/µL.
• Platelet count = 100,000/µL (without transfusion within 2 weeks of laboratory test used to determine eligibility)
• Haemoglobin = 9.0 g/dL (without transfusion within 2 weeks of laboratory test used to determine eligibility)
• INR or aPTT = 1.5 × upper limit of normal (ULN). This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
• AST, ALT, and alkaline phosphatase = 2.5 times the upper limit of normal (ULN), except if alkaline phosphatase >2.5 times the ULN, then AST and/or ALT must be = 1.5 × ULN
• Serum bilirubin = 1.0 × ULN. Patients with known Gilbert disease who have serum bilirubin level < 3 × ULN may be enrolled.
• Serum creatinine = 1.5 × ULN
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 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). No hormonal methods and preferably barrier method always containing a spermicide, intrauterine device (I

Exclusion Criteria

1. Patients with a known sensitizing mutation in the epidermal growth factor receptor (EGFR) gene, ALK translocations or ROS1 mutations
2. Weight loss >10% within the previous 3 months
3. Patients with uncontrolled neuropathy (sensory) grade 2 or greater regardless of cause according to CTCAE v5.0
4. Major surgery within 28 days of study day 1
5. Significant gastrointestinal disorder that results in significant malabsorption, requirement for intravenous alimentation, or inability to take oral medication
6. Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 6 months prior to study day 1, unstable arrhythmias or unstable angina
7. Ongoing cardiac dysrhythmias of CTCAE grade =2, uncontrolled atrial fibrillation of any grade or QTcF interval > 470ms
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
11. Patients with vena cava syndrome 12. Malignant pleural or pericardial effusion: both will be considered as suggestive of metastatic disease. 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.
13. Prior treatment with anti-neoplasic drugs
14. Malignancies other than NSCLC within 3 years prior to enrollment (except for adequately treated non-melanoma skin cancer, basal cell cancer, carcinoma in situ of the cervix, localized prostate cancer treated surgically with curative intent, which were allowed within 3 years)
15. Women who are pregnant, lactating, or intending to become pregnant during the study.
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.
17. Patients with active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C.
-Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and absence of HBsAg) are eligible only if they are negative for HBV DNA.
-Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA.
18. Active tuberculosis.
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.
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
22. Evidence of any other disorder or significant laboratory finding that makes the patient undesirable to participate in the study
23. Use of strong inducers of CYP3A4 (including herbal supplements such as St John’s wort) within 14 days of half-lives (whichever is longer) prior to study day 1
24. Use of proton pump inhibitors within 14 d

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

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