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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion GECP

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

25 May 2022 → ongoing

Decision date (initial)

2024-06-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Fundación GECP

External identifiers

EU CT number

2024-511268-10-00

EudraCT number

2021-004576-34

ClinicalTrials.gov

NCT05398094

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

"To evaluate the efficacy of induction treatment of AMG510 (Sotorasib) plus AMG510 (Sotorasib) treatment post-induction as measured by Progression Free Survival at 6 months (PFS6)"

Secondary objectives 5

1. 1. To evaluate the Overall response rate (ORR) of AMG510 (Sotorasib) as measured by investigator after induction treatment.
2. 2. To evaluate the Overall Survival (OS) rate at 6 month, 1 year and 2 years of treatment with AMG510 (Sotorasib)
3. 3. To evaluate the sites of first failure
4. 4. To evaluate the safety and tolerability of AMG510 (Sotorasib)
5. 5. To evaluate number of patients that become resectable after induction treatment

Conditions and MedDRA coding

Unresectable stage III (IIIA-N2, IIIB, IIIC) KRAS p.G12C non-small cell lung cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

1. 1. Male or female, aged ≥ 18 years old
2. 2. ECOG performance status of 0-1
3. "3. Histologically or cytologically confirmed, unresectable Stage III (IIIA, IIIB and IIIC) NSCLC according to 8th version of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology : a. Patients Stage III that did not respond to or progressed on to concurrent chemoradiotherapy could be included. Note: between 2-4 weeks should elapse between the end of radiotherapy and the start of Sotorasib b. Patients that did not respond or progressed on induction chemotherapy (without RT) could be included. c. Patients Stage III who are considered ineligible for concurrent chemo-radiotherapy due to: i. Tumor size ≥ 5 cm and lymph node N2 involvement ii. 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 iii. Prior treatment with thoracic radiotherapy for any reason iv. Or under decision of a tumor committee as inappropriate due to local characteristics to perform treatment upfront d. Patients Stage III eligible for sequential chemo-radiotherapy but as per investigator criteria Sotorasib monotherapy is the preferred option, can be included "
4. "4. Subjects that receive radiotherapy before inclusion in MERIT-lung clinical trial must have recovered from all radiotherapy related toxicity with the exception of alopecia (any grade of alopecia allowed) "
5. 5. Patients who have documentation of KRAS p.G12C prior to enrolment. This determination can be done either by solid or liquid biopsy.
6. 6. Having a life expectancy ≥ 12 weeks
7. 7. PET-CT at baseline is mandatory to confirm the absence of distant disease and to confirm unresectable disease
8. 8. 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.
9. 9. Brain CT or MRI is mandatory
10. 10. Patients with at least 1 measurable lesion, as defined by RECIST v1.1.
11. "11. Adequate hematologic and organ function defined by the following laboratory results obtained within 14 days prior to enrolment: · 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"
12. "12. 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."
13. 13. Willingness and ability to comply with scheduled visits and study procedures.
14. "14. For female patients of childbearing potential, a negative pregnancy test must have been documented prior to enrolment (within 14 days prior to enrolment)."
15. "15. 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 (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."
16. "16. 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)."
17. "17. 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 enrolment."
18. "18. QTc interval must be ≤ 470 msec in females and ≤ 450 msec in males, based on the average obtained from three ECG."

Exclusion criteria 25

1. 1. Patients with a known sensitizing mutation in the epidermal growth factor receptor (EGFR) gene, ALK translocations or ROS1 mutations
2. 2. Weight loss >10% within the previous 3 months
3. 3. Patients with uncontrolled neuropathy (sensory) grade 2 or greater regardless of cause according to CTCAE v5.0
4. 4. Major surgery within 28 days of enrolment
5. "5. Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to CTCAE version 5.0 grade 0 or 1, or to levels dictated in the eligibility criteria with the exception of alopecia (any grade allowed) or toxicities from prior anti-tumor therapy that are considered irreversible (defined as having been present and stable for > 6 months); endocrine adverse events that are stably maintained on appropriate replacement therapy are allowed"
6. 6. Significant gastrointestinal disorder that results in significant malabsorption, requirement for intravenous alimentation, or inability to take oral medication
7. 7. Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 6 months prior to enrolment, unstable arrhythmias or unstable angina
8. "8. Ongoing cardiac dysrhythmias of CTCAE grade ≥2, uncontrolled atrial fibrillation of any grade or QTcF interval > 470ms"
9. 9. Severe infections within 4 weeks prior to enrolment including, but not limited to hospitalization for complications of infection, bacteraemia or severe pneumonia
10. 10. Therapeutic oral or intravenous antibiotics within 2 weeks prior to enrolment
11. 11. Patients with any concomitant and uncontrolled medical disorder
12. 12. Patients with vena cava syndrome
13. "13. 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."
14. "14. Malignancies other than NSCLC within 3 years prior to enrolment (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. 15. Women who are pregnant, lactating, or intending to become pregnant during the study
16. "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. "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. 18. Active tuberculosis.
19. "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. "20. Patients with illnesses or conditions that interfere with their capacity to understand follow and/or comply with study procedures."
21. 21. Known or suspected hypersensitivity to drugs with similar chemical structures to the study drug
22. 22. Evidence of any other disorder or significant laboratory finding that makes the patient undesirable to participate in the study
23. 23. Use of strong inducers of CYP3A4 (including herbal supplements such as St John’s wort) within 14 days or 5 of half-lives (whichever is longer) prior to enrolment
24. 24. Use of proton pump inhibitors within 14 days to enrolment
25. 25. Previous treatment with sotorasib or other KRASG12C inhibitor

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. "Primary-PFS will be defined as the time from the date of first dose of induction treatment until the date of first objective disease progression or death. The PFS6 will be defined as the Kaplan-Meier estimate of PFS at 6 months. Progression will be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1"

Secondary endpoints 5

1. 1. Overall response rate (ORR) is defined as the proportion of patients who have a partial or complete response to therapy; it does not include stable disease and is a direct measure of drug tumoricidal activity.
2. 2. Overall Survival (OS) rate of live patients from enrollment until 6 months, 1 year and 2 years of treatment.
3. 3. Sites of first failure
4. 4. To evaluate the safety and tolerability of AMG510 (Sotorasib)
5. 5. To evaluate number of patients that become resectable after induction treatment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion GECP

Sponsor organisation

Fundacion GECP

Address

Avinguda Meridiana 358 6 Planta

City

Barcelona

Postcode

08027

Country

Spain

Scientific contact point

Organisation

Fundacion GECP

Contact name

Mariano Provencio

Public contact point

Organisation

Fundacion GECP

Contact name

Maria Fernández

Locations

1 EU/EEA country · 20 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications