Advanced non-small cell lung cancer harboring the KRAS G12C mutation MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Novartis Farmacéutica, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
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 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 360 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: ? To compare the progression-free survival (PFS) of JDQ443 versus docetaxel;Primary end point(s): ? Progression-free survival (PFS) per Blinded Independent Review Committee (BIRC) according to RECIST 1.1.;Secondary Objective: ? 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;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 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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;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 | — |
Countries
Argentina, Brazil, Bulgaria, Canada, Chile, China, Colombia, Croatia, Czechia, Denmark, Estonia, Finland, Greece, Hong Kong, Hungary, Iceland, India, Italy, Jordan, Korea, Republic of, Lebanon, Malaysia, Mexico, Norway, Poland, Portugal, Romania, Russian Federation, Serbia, Slovenia, Spain, Taiwan, Thailand, United Kingdom, Viet Nam
Contacts
Public ContactTrial Monitoring Organization (TMo)
Novartis Farmacéutica, S.A.
Outcome results
None listed