AMG 510 Expanded Access Protocol in Selected European Countries

Phase 1

• Conditions: Previously Treated Locally Advanced and Unresectable or Metastatic Non-small Cell Lung Cancer with KRAS p.G12C Mutation; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-005279-11-ES
• Lead Sponsor: Amgen, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-09-01
• Last Update Posted: 7 September 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 638

Inclusion Criteria

- Subject has provided informed consent prior to initiation of any study specific activities/procedures.
- Age = 18 years.
- Pathologically documented, locally-advanced, and unresectable or metastatic non-small cell lung cancer.
- Have documentation of KRAS p.G12C mutation per local testing guidelines or a screening for another Amgen sotorasib study.
- Subject has exhausted other standard of care options for locally advanced and unresectable or metastatic disease including platinum-based combination chemotherapy, PD-1/PD-L1 immunotherapy, and docetaxel (unless contraindicated).
- Eastern Cooperative Oncology Group (ECOG) performance status = 2
- Adequate hematologic and end-organ function, defined as the following:
- Absolute neutrophil count (ANC) > 1000 cells/µl (without granulocyte colony-stimulating factor support within 2 weeks of laboratory test used to determine eligibility)
- Hemoglobin = 9.0 g/dL
- Platelet count = 75 000/µL
- AST and ALT < 2.5 x the upper limit of normal (ULN) (if liver metastases are present, = 5 x ULN)
- Total bilirubin < 1.5 x ULN (subjects with known Gilbert’s disease with serum bilirubin < 3 x ULN may be enrolled if direct bilirubin is < 1 x ULN and approved by Amgen Medical Monitor)
- International normalized ratio (INR) or activated partial thromboplastin time (aPTT) < 1.5 x ULN
- Serum creatinine = 1.5 x ULN OR estimated glomerular filtration rate (eGFR) = 45 mL/min/1.73 m2. Modification of Diet in Renal Disease formula should be used for eGFR calculation.
108 QTc = 470 msec in women and = 450 msec in men
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 375
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 263

Exclusion Criteria

- Mixed small-cell lung cancer and NSCLC histology
- Subjects with symptomatic CNS metastases who are neurologically unstable or have required increasing doses of steroids to manage CNS symptoms within the 2 weeks prior to study day 1
Other Medical Conditions
- Subjects with active hepatitis B (positive hepatitis B surface antigen [HBsAg]) or hepatitis C virus (HCV) (positive HCV RNA)
- Subjects 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
- HBV carriers or those subjects receiving antiviral therapy for HBV or HCV are not eligible to participate
- Subjects positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA
- Current active malignancy other than NSCLC with the exception of those with a negligible risk of metastases or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal cell carcinoma, cutaneous squamous cell carcinoma, localized prostate cancer treated with curative intent, or ductal carcinoma in situ treated surgically with curative intent).
- Leptomeningeal disease
- Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (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
- History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined in Section 5.2) that, in the opinion of the investigator or medical monitor, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
- Significant gastrointestinal disorder that results in significant malabsorption, requirement for intravenous alimentation, or inability to take oral medication
- Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 6 months prior to enrollment, unstable arrhythmias or unstable angina
- Severe infections within 4 weeks prior to enrollment including, but not limited to hospitalization for complications of infection, bacteremia or severe pneumonia.
- Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, retinoid therapy, hormonal therapy [except for subjects with history of completely resected breast cancer with no active disease on long term adjuvant endocrine therapy], or investigational agent) within 4 weeks (chemotherapy within 2 weeks)
of study day 1. Targeted small molecule inhibitors, within 14 days of study day 1, or within 5 half-lives, whichever is longer. Please note that bisphosphonates or anti-RANKL antibody therapy is allowed if needed for management of hypercalcemia or for prevention
of skeletal related events
- Therapeutic or palliative radiation therapy within 2 weeks of study day 1. Subjects must have recovered from all radiotherapy related toxicity to CTCAE version 5.0 grade 1 or less with the exception of alopecia (any grade of alopecia allowed).
- Use of known cytochrome P450 (CYP)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: - To provide expanded access and to characterize the safety profile of sotorasib in subjects with previously treated locally advanced unresectable/metastatic non-small cell lung cancer (NSCLC) with Kirsten rat sarcoma viral oncogene homolog (KRAS) p.G12C mutation;Secondary Objective: - To describe and collect testing modalities in KRAS p.G12C-positive NSCLC subjects<br>- To evaluate the duration of treatment with sotorasib;Primary end point(s): -Incidence of treatment-emergent adverse events (TEAE), adverse event of interest, treatment-related adverse events, serious TEAE, TEAE leading to discontinuation of sotorasib;Timepoint(s) of evaluation of this end point: The exact timing of the primary analysis will be based on subject enrollment and will occur after sotorasib receives marketing authorization approval for the treatment of NSCLC for all participating countries in which subjects were enrolled.<br><br>A final analysis will occur when all enrolled subjects have completed the study.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - KRAS p.G12C testing modalities<br>- Treatment duration;Timepoint(s) of evaluation of this end point: The exact timing of the primary analysis will be based on subject enrollment and will occur after sotorasib receives marketing authorization approval for the treatment of NSCLC for all participating countries in which subjects were enrolled.<br><br>A final analysis will occur when all enrolled subjects have completed the study.