E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced non-small cell lung cancer harboring the KRAS G12C mutation |
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E.1.1.1 | Medical condition in easily understood language |
Advanced lung cancer with a specific mutation (G12C) in the KRAS gene |
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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 | 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 |
● To compare the progression-free survival (PFS) of JDQ443 versus docetaxel |
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E.2.2 | Secondary objectives of the trial |
● To compare overall survival (OS) in the two treatment arms (key secondary objective) ● To assess the anti-tumor activity of JDQ443 compared to docetaxel ● To assess PFS2 in the two treatment arms ● To characterize the safety profile of JDQ443 ● To assess the effect of JDQ443 vs docetaxel on PROs (NSCLC-SAQ, EORTC QLQ-C30, lung-specific module QLQ-LC13, and EQ-5D-5L) including lung cancer symptoms, health-related quality of life, and health status. ● To characterize the pharmacokinetics of JDQ443. ● To assess the effect of JDQ443 vs docetaxel on ECOG performance status. ● To assess the safety of JDQ443 in participants who crossover from docetaxel.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
● Participants are male and female, aged 18 or older. ● Histologically confirmed locally advanced stage IIIB/IIIC (and not eligible for definitive chemo-radiation curative therapy or complete surgical resection) or stage IV previously treated NSCLC. Presence of a KRAS G12C mutation by central laboratory testing using tissue samples. ● Participants have received one prior platinum-based chemotherapy and one prior immune checkpoint inhibitor therapy either in combination or in sequence. ● Participants with ECOG performance status from 0 to 2
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E.4 | Principal exclusion criteria |
● Participants who have previously received docetaxel, KRAS G12C inhibitor, or any other systemic therapy for their locally advanced or metastatic NSCLC other than one platinum-based chemotherapy and one prior immune checkpoint inhibitor therapy. ● Participants with epidermal growth factor receptor (EGFR)-sensitizing mutation and/or anaplastic lymphoma kinase (ALK) rearrangement by local testing. Participants with other known druggable alterations will be excluded, if required by local guidelines. ● History of severe hypersensitivity reaction to taxanes or any excipients of these study treatments.
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E.5 End points |
E.5.1 | Primary end point(s) |
● Progression-free survival (PFS) per Blinded Independent Review Committee (BIRC) according to RECIST 1.1. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary PFS analysis for the randomized part of the study will be performed after observing approximately 269 centrally confirmed PFS events, in the full analysis set (FAS) or based on the PFS interim analysis data in case the study is futile at that analysis. If PFS is statistically significant, the final OS analysis will be performed after observing approximately 228 deaths in the FAS or earlier if OS meets statistical significance at the planned interim analysis
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E.5.2 | Secondary end point(s) |
● OS ● ORR, DCR, TTR, and DOR per RECIST 1.1 (by BIRC and local Investigator's assessment) ● PFS2 based on local investigator's assessment ● Type, frequency and severity of adverse events, changes in laboratory values, vital signs, ECGs ● Time to definitive 10-point deterioration symptom scores of chest pain, cough, and dyspnea per QLQ-LC13 questionnaire are primary PRO variables of interest ● Time to definitive deterioration in global health status/QoL, shortness of breath, and pain per QLQ-C30 are secondary PRO variables of interest ● Change from baseline in EORTC-QLQ C30 LC13, EQ-5D-5L, and NSCLC-SAQ ● The concentration of JDQ443 in plasma and pharmacokinetic parameters for a subgroup of participants in mainland China. ● Time to definitive deterioration of the ECOG performance status. ● Type, frequency and severity of adverse events, changes in laboratory values, vital signs, ECGs
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Efficacy: pre specified time-points as per protocol • Safety/tolerability: continuously during on-treatment period • PK: as defined per protocol and Statistical Analysis Plan
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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 | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | No |
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 | Yes |
E.8.2.3.1 | Comparator description |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 57 |
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 |
Argentina |
Chile |
Colombia |
Malaysia |
Hong Kong |
Taiwan |
Brazil |
Canada |
China |
India |
Jordan |
Korea, Republic of |
Lebanon |
Mexico |
Russian Federation |
Serbia |
Thailand |
United Kingdom |
Viet Nam |
Bulgaria |
Croatia |
Czechia |
Denmark |
Estonia |
Finland |
Greece |
Hungary |
Iceland |
Italy |
Norway |
Poland |
Portugal |
Romania |
Slovenia |
Spain |
Türkiye |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 28 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |