E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
KRAS p.G12C mutant untreated stage IV Non-Small Cell Lung Cancer (NSCLC) |
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E.1.1.1 | Medical condition in easily understood language |
Non-small cell lung cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029522 |
E.1.2 | Term | Non-small cell lung cancer stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To evaluate the tumor objective response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria in subjects who receive sotorasib at either 960 mg daily (QD) or 240 mg QD whose tumors are programmed death ligand 1 (PD L1) Tumor Proportion Score (TPS) < 1% and/or harbor a serine/threonine kinase 11 (STK11) co mutation, in a subgroup of subjects with PD L1 < 1% and in a subgroup of subjects with STK11 co mutation. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate other measures of efficacy. - To evaluate the safety and tolerability of sotorasib. - Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral tablet formulation |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Adult (= or > 18 years old) with NSCLC • Untreated Stage IV metastatic disease. Participants 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 • Pathologically documented metastatic NSCLC with KRAS G12C mutation (local confirmation) • Programmed death-ligand 1 (PD-L1) TPS Score < 1% and/or serine/threonine kinase 11 (STK11) co-mutation (local confirmation) • Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 • No active brain metastases • Measurable disease per investigator interpretation using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria |
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E.4 | Principal exclusion criteria |
• Mixed small-cell lung cancer and NSCLC histology • Active brain metastases from non-brain tumors • Myocardial Infarction within 6 months of study Day 1 • Use of proton-pump inhibitors (PPIs), histamine (H2) receptor antagonists (H2RA), strong inducers of cytochrome P450 (CYP) 3A4 (CYP3A4) or known CYP3A4 sensitive substrates or P-gp substrates • Therapeutic or palliative radiation therapy within 2 weeks of study day 1 • Unable to take oral medication • Unable to receive both iodinated contrast for computed tomography (CT) scans and gadolinium contrast for magnetic resonance imagine (MRI) scans |
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective response (OR) (OR = complete response [CR] + partial response [PR]), measured by computed tomography (CT) or magnetic resonance imaging (MRI) and assessed per RECIST v1.1 per Blinded Independent Central Review (BICR) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Safety data will be reviewed on an ongoing basis by Amgen. - The primary analysis is planned approximately 6 months after all subjects are enrolled and have had the opportunity to complete at least 1 post-baseline tumor assessment. - The futility analysis will occur after approximately 60 subjects across 2 treatment dose arms become response evaluable, defined as received at least 1 dose of sotorasib and had been enrolled for at least 7 weeks. - The final analysis will occur when the end of study. |
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E.5.2 | Secondary end point(s) |
• Disease control (CR +PR + stable disease [SD]) • Duration of response (DOR) • Time to response (TTR) • Progression-free survival (PFS) • Overall survival (OS) • Treatment emergent adverse events, treatment-related adverse events, and changes in vital signs, electrocardiogram [ECGs], and clinical laboratory tests. • PK parameters of sotorasib including, but not limited to, maximum plasma concentration (Cmax), time to achieve Cmax (tmax), and area under the plasma concentration-time curve (AUC). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Safety data will be reviewed on an ongoing basis by Amgen. - The primary analysis is planned approximately 6 months after all subjects are enrolled and have had the opportunity to complete at least 1 post-baseline tumor assessment. - The futility analysis will occur after approximately 60 subjects across 2 treatment dose arms become response evaluable, defined as received at least 1 dose of sotorasib and had been enrolled for at least 7 weeks. - The final analysis will occur when the end of study. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Turkey |
United States |
Belgium |
Denmark |
France |
Germany |
Italy |
Sweden |
Netherlands |
Spain |
Switzerland |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of study date is defined as the date when the last subject across all sites is assessed or receives an intervention for evaluation in the study (ie, last subject last visit), including any additional parts in the study (eg, LTFU, additional antibody testing), as applicable. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |