E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Non-Small Cell Lung Cancer |
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E.1.1.1 | Medical condition in easily understood language |
Advanced Non-Small Cell Lung Cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
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 | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
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 |
This Phase 3 study will evaluate the efficacy of the investigational agent MRTX849 versus docetaxel in patients who have been previously treated for metastatic NSCLC with a KRAS G12C mutation. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate secondary efficacy endpoints in the study population. • To evaluate the safety and tolerability in the study population. • To evaluate the pharmacokinetics (PK) of MRTX849 administered in the study population. • To evaluate health-related quality of life (HRQOL) and lung cancer-specific symptoms in the study population.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologically or cytologically confirmed diagnosis of NSCLC with KRAS G12C mutation. • Candidacy to receive treatment with docetaxel.
Crossover inclusion criteria 1. Evidence of RECIST 1.1 defined disease progression on docetaxel per BICR 2. EGOG performance status 0-2. |
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E.4 | Principal exclusion criteria |
• Prior treatment with an agent targeting KRAS G12C (e.g., AMG 510, sotorasib). • Active brain metastases.
Crossover Exclusion Criteria: 1. Receipt of any other systemic anti-cancer therapy after last administration of docetaxel on the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Progression-free Survival (PFS) Defined as time from randomization until disease progression or death from any cause, whichever occurs first.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints: - Overall Survival (OS) − Objective Response Rate (ORR), − Duration of Response (DOR), and − 1-Year Survival Rate. • Safety characterized by type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events (AEs), laboratory abnormalities, and number of patients discontinuing study treatment due to an adverse event. • Population PK parameters of MRTX849. • Patient Reported Outcome (PRO) scores using the following: − Lung Cancer Symptom Scale (LCSS), and − European Quality of Life Five Dimensions Questionnaire (EQ-5D-5L
− Duration of Response (DOR), and − 1-Year Survival Rate. • Plasma PK parameters of MRTX849 (and metabolites, if applicable). • Patient Reported Outcome (PRO) scores using the following: − Lung Cancer Symptom Scale (LCSS), and − European Quality of Life Five Dimensions Questionnaire (EQ-5D-5L). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
32 months (Primary efficacy endpoint PFS and Secondary efficacy endpoint ORR) and 49 months (all other secondary endpoints) |
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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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
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 | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 200 |
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 |
Chile |
Costa Rica |
Singapore |
Switzerland |
Ireland |
Hong Kong |
Puerto Rico |
Australia |
Austria |
Belgium |
China |
Czechia |
France |
Germany |
Greece |
Hungary |
Italy |
Korea, Republic of |
Netherlands |
Poland |
Portugal |
Romania |
Russian Federation |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |