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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT04699188
Registration number
NCT04699188
Ethics application status
Date submitted
5/01/2021
Date registered
7/01/2021
Titles & IDs
Public title
Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation
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Scientific title
A Phase Ib/II Open-label, Multi-center Dose Escalation Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation
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Secondary ID [1]
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0
2020-004129-22
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Secondary ID [2]
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0
CJDQ443A12101
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Universal Trial Number (UTN)
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Trial acronym
KontRASt-01
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
KRAS G12C Mutant Solid Tumors
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0
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Carcinoma, Non-Small-Cell Lung
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0
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Carcinoma, Colorectal
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0
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Cancer of Lung
0
0
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Cancer of the Lung
0
0
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Lung Cancer
0
0
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Neoplasms, Lung
0
0
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Neoplasms, Pulmonary
0
0
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Pulmonary Cancer
0
0
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Pulmonary Neoplasms
0
0
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Condition category
Condition code
Cancer
0
0
0
0
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Non melanoma skin cancer
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Cancer
0
0
0
0
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Kidney
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Cancer
0
0
0
0
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Lung - Mesothelioma
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Cancer
0
0
0
0
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Lung - Non small cell
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Cancer
0
0
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0
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Lung - Small cell
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Cancer
0
0
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0
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Bowel - Back passage (rectum) or large bowel (colon)
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - JDQ443
Treatment: Drugs - TNO155
Treatment: Other - tislelizumab
Experimental: Arm A - JDQ443
Experimental: Arm B - JDQ443 in combination with TNO155
Experimental: Arm C - JDQ443 in combination with tislelizumab
Experimental: Arm D - JDQ443 in combination with TNO155 and tislelizumab
Treatment: Drugs: JDQ443
KRAS G12C inhibitor
Treatment: Drugs: TNO155
SHP2 inhibitor
Treatment: Other: tislelizumab
Anti PD1 antibody
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Intervention code [1]
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Treatment: Drugs
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Intervention code [2]
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Treatment: Other
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Dose Escalation: Incidence and severity of dose limiting toxicities (DLTs) during the first cycle of monotherapy or combination treatment
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Assessment method [1]
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A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment
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Timepoint [1]
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21 days
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Primary outcome [2]
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Dose Escalation: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
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Assessment method [2]
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All information obtained on AE will be displayed by treatment group. Summary tables will include only AEs that started/worsened during the cycles of treatment (treatment-emergent AEs).
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Timepoint [2]
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24 months
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Primary outcome [3]
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Dose Escalation: Frequency of dose interruptions and reductions, by treatment
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Assessment method [3]
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Tolerability of study drug will be assessed by summarizing the number of and reason for dose delays and dose reductions.
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Timepoint [3]
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24 months
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Primary outcome [4]
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Dose Escalation: Dose intensity by treatment
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Assessment method [4]
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0
Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of treatment.
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Timepoint [4]
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24 months
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Primary outcome [5]
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Dose Expansion: Overall response rate (ORR) per RECIST v1.1, by treatment
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Assessment method [5]
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Overall response rate is defined as the proportion of patients with a BOR of CR or PR according to RECIST 1.1, and will be summarized along with the corresponding 95% exact binomial confidence interval (CI). Applies to all groups except the brain metastasis group.
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Timepoint [5]
0
0
24 months
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Primary outcome [6]
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Dose expansion: Overall intracranial response rate (OIRR) per mRANO-BM
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Assessment method [6]
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OIRR per mRANO-BM is defined as the proportion of participants with a best overall intracranial response (BOIR) of CR or PR according to mRANO-BM criteria, and will be summarized along with the corresponding 90% and 95% exact CI. Applies to brain metastasis group only.
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Timepoint [6]
0
0
24 months
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Primary outcome [7]
0
0
Dose expansion: Incidence and severity of AEs and SAEs
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Assessment method [7]
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All information obtained on AE will be displayed by treatment group. Summary tables will include only AEs that started/worsened during the cycles of treatment (treatment-emergent AEs). Applies to JDQ443 dose randomization group only.
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Timepoint [7]
0
0
24 months
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Primary outcome [8]
0
0
Dose expansion: frequency of dose interruptions and reductions, by treatment
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Assessment method [8]
0
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Tolerability of study drug will be assessed by summarizing the number of and reason for dose delays and dose reductions. Applies to JDQ443 dose randomization group only.
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Timepoint [8]
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24 months
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Primary outcome [9]
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Dose expansion: Dose intensity by treatment
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Assessment method [9]
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Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of treatment. Applies to JDQ443 dose randomization group only
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Timepoint [9]
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24 months
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Primary outcome [10]
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Dose expansion: ORR per RECIST 1.1 of JDQ443 single agent in patients with non-small cell lung cancer (JDQ443 dose randomization group only)
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Assessment method [10]
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Overall response rate is defined as the proportion of patients with BOR of CR or PR according to RECIST 1.1, and will be summarized along with the corresponding 95% exact binomial confidence interval (CI). Applies to JDQ443 dose randomization group only
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Timepoint [10]
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24 months
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Secondary outcome [1]
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Dose Escalation and Expansion: ORR per RECIST v1.1
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Assessment method [1]
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Overall response rate is defined as the proportion of patients with a BOR of CR or PR according to RECIST 1.1, and will be summarized along with the corresponding 95% exact binomial confidence interval (CI)
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Timepoint [1]
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24 months
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Secondary outcome [2]
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Dose Escalation and Expansion: Best Overall Response (BOR) per RECIST v1.1
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Assessment method [2]
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BOR is defined as the best overall confirmed response recorded from the start of the treatment until disease progression/recurrence.
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Timepoint [2]
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24 months
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Secondary outcome [3]
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Dose Escalation and Expansion: Progression-free survival (PFS) per RECIST v1.1, Overall Survival (OS)
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Assessment method [3]
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Per RECIST 1.1, PFS is defined as the time from the date of start of treatment to the date of the first documented progression, or death. If patient has not had an event, PFS will be censored at the date of last adequate tumor assessment. PFS will be summarized using the Kaplan-Meier method, along with 95% CI
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Timepoint [3]
0
0
24 months
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Secondary outcome [4]
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Dose Escalation and Expansion: Duration of Response (DOR) per RECIST v1.1
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Assessment method [4]
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Duration of response is defined as the time from the date of the first documented response (CR or PR), to the date of first documented progression, or death due any cause. Estimates will use Kaplan-Meier method, and median DOR and corresponding 95% CI will be presented.
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Timepoint [4]
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24 months
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Secondary outcome [5]
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Dose Escalation and Expansion: Disease Control Rate (DCR) per RECIST v1.1
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Assessment method [5]
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The disease control rate is calculated as the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease. It will be summarized along with the corresponding 95% exact CI
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Timepoint [5]
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24 months
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Secondary outcome [6]
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Dose Escalation and Expansion: Plasma or serum concentration vs time profiles (AUC) by treatment
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Assessment method [6]
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AUC is defined as area under the plasma or serum concentration versus time curve after a dose of JDQ443, TNO155 and tislelizumab
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Timepoint [6]
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Up to 24 months
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Secondary outcome [7]
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Dose Escalation and Expansion: Plasma concentration (Cmax) by treatment
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Assessment method [7]
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Cmax is defined as the maximum observed plasma or serum drug concentration after single dose administration.
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Timepoint [7]
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Up to 24 months
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Secondary outcome [8]
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Dose Escalation and Expansion: Time to achieve Cmax (Tmax) by treatment
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Assessment method [8]
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Tmax is defined as the time to reach maximum plasma or serum drug concentration after single dose administration.
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Timepoint [8]
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Up to 24 months
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Secondary outcome [9]
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Dose Escalation and Expansion: Antidrug antibody (ADA) incidence by treatment
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Assessment method [9]
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To evaluate the immunogenicity of tislelizumab when dosed in combination with JDQ443 and/or TNO155 - only applicable to Arms C and D
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Timepoint [9]
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Up to 24 months
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Secondary outcome [10]
0
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Dose Expansion: Dose intensity by treatment
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Assessment method [10]
0
0
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Timepoint [10]
0
0
24 months
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Secondary outcome [11]
0
0
Dose Expansion: Frequency of dose interruptions and reductions, by treatment
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Assessment method [11]
0
0
Tolerability of study drug will be assessed by summarizing the number of and reason for dose delays and dose reductions.
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Timepoint [11]
0
0
24 months
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Secondary outcome [12]
0
0
Dose Expansion: Incidence and severity of dose limiting toxicities (DLTs) during the first cycle of monotherapy or combination treatment
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Assessment method [12]
0
0
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment
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Timepoint [12]
0
0
21 days
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Secondary outcome [13]
0
0
Dose Expansion: Incidence and severity of AEs and SAEs by treatment
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Assessment method [13]
0
0
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Timepoint [13]
0
0
24 months
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Secondary outcome [14]
0
0
Dose expansion: Intracranial disease control rate (IDCR) per mRANO-BM
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Assessment method [14]
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IDCR is the proportion of participants with a confirmed BOIR of CR or PR or SD (or non-CR/non-PD) per mRANO-BM criteria. It will be summarized along with the corresponding 90% and 95% CI. Applies to the brain metastasis group only.
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Timepoint [14]
0
0
24 months
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Secondary outcome [15]
0
0
Dose expansion: Best overall intracranial response (BOIR) per mRANO-BM
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Assessment method [15]
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BOIR is defined as the best overall confirmed response recorded from the start of the treatment until disease progression/recurrence per mRANO-BM, or until patient comes off study, whichever comes first. BOIR will be summarized along with the corresponding 95% exact CI. Applies to the brain metastasis group only.
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Timepoint [15]
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24 months
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Secondary outcome [16]
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Dose expansion: Intracranial progression free survival (IPFS) per mRANO-BM
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Assessment method [16]
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IPFS is defined as the time from the date of start of treatment to the date of the first documented progression per mRANO-BM, or death due to any cause. If a patient has not had an event, IPFS will be censored at the date of last adequate tumor assessment. IPFS will be summarized using the Kaplan-Meier method. Median IPFS and IPFS probability at pre specified time-points will be presented along with 95% CI. Applies to the brain metastasis group only.
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Timepoint [16]
0
0
24 months
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Secondary outcome [17]
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Dose expansion: Duration of intracranial response (DOIR) per mRANO-BM
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Assessment method [17]
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DOIR is defined as the time from the date of first documented intracranial response of either CR or PR to the date of the first documented intracranial progression as per mRANO-BM criteria as assessed by central review or date of death due to underlying cause of cancer. DOIR will be summarized using the KM method if data permit. Median DOIR, with corresponding 95% CI. KM estimates for DOIR proportions at specific time points, along with 95% CI will also be provided. Applies to the brain metastasis group only.
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Timepoint [17]
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24 months
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Eligibility
Key inclusion criteria
* Adult patients with advanced (metastatic or unresectable) KRAS G12C mutant solid tumors who have received standard of care or are intolerant or ineligible to approved therapies
* ECOG Performance Status of 0 or 1
* At least one measurable lesion as defined by RECIST 1.1
* Prior treatment with a KRAS G12C inhibitor may be allowed for dose escalations of combinations and a subset of groups in dose expansion
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
* Tumors harboring driver mutations that have approved targeted therapies, with the exception of KRAS G12C mutations
* Symptomatic brain metastases or known leptomeningeal disease. Patients with asymptomatic treated or untreated brain metastases may be eligible
* Clinically significant cardiac disease or risk factors at screening
* A medical condition that results in increased photosensitivity Other protocol-defined inclusion/exclusion criteria may apply.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
24/02/2021
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
8/01/2027
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Actual
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Sample size
Target
475
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
VIC
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Recruitment hospital [1]
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Novartis Investigative Site - Melbourne
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Recruitment postcode(s) [1]
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3000 - Melbourne
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Recruitment outside Australia
Country [1]
0
0
United States of America
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State/province [1]
0
0
Georgia
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Country [2]
0
0
United States of America
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State/province [2]
0
0
Massachusetts
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Country [3]
0
0
United States of America
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State/province [3]
0
0
Missouri
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Country [4]
0
0
United States of America
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State/province [4]
0
0
Oregon
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Country [5]
0
0
United States of America
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State/province [5]
0
0
Pennsylvania
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Country [6]
0
0
United States of America
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State/province [6]
0
0
Texas
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Country [7]
0
0
Belgium
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State/province [7]
0
0
Leuven
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Country [8]
0
0
Canada
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State/province [8]
0
0
Quebec
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Country [9]
0
0
China
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State/province [9]
0
0
Fujian
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Country [10]
0
0
China
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State/province [10]
0
0
Guangdong
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Country [11]
0
0
China
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State/province [11]
0
0
Jiangxi
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Country [12]
0
0
China
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State/province [12]
0
0
Beijing
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Country [13]
0
0
Denmark
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State/province [13]
0
0
Copenhagen
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Country [14]
0
0
France
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State/province [14]
0
0
Lyon
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Country [15]
0
0
France
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State/province [15]
0
0
Marseille
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Country [16]
0
0
France
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State/province [16]
0
0
Villejuif
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Country [17]
0
0
Germany
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State/province [17]
0
0
Dresden
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Country [18]
0
0
Germany
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State/province [18]
0
0
Essen
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Country [19]
0
0
Germany
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State/province [19]
0
0
Freiburg
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Country [20]
0
0
Germany
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State/province [20]
0
0
Koeln
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Country [21]
0
0
Hong Kong
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State/province [21]
0
0
Hong Kong
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Country [22]
0
0
Italy
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State/province [22]
0
0
BS
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Country [23]
0
0
Italy
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State/province [23]
0
0
MI
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Country [24]
0
0
Japan
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State/province [24]
0
0
Aichi
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Country [25]
0
0
Japan
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State/province [25]
0
0
Chiba
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Country [26]
0
0
Japan
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State/province [26]
0
0
Kanagawa
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Country [27]
0
0
Japan
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State/province [27]
0
0
Osaka
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Country [28]
0
0
Japan
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State/province [28]
0
0
Tokyo
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Country [29]
0
0
Korea, Republic of
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State/province [29]
0
0
Seoul
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Country [30]
0
0
Netherlands
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State/province [30]
0
0
Amsterdam
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Country [31]
0
0
Singapore
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State/province [31]
0
0
Singapore
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Country [32]
0
0
Spain
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State/province [32]
0
0
Andalucia
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Country [33]
0
0
Spain
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State/province [33]
0
0
Catalunya
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Country [34]
0
0
Spain
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State/province [34]
0
0
Comunidad Valenciana
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Country [35]
0
0
Spain
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State/province [35]
0
0
Galicia
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Country [36]
0
0
Spain
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State/province [36]
0
0
Madrid
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Country [37]
0
0
Taiwan
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State/province [37]
0
0
Tainan
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Country [38]
0
0
Taiwan
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State/province [38]
0
0
Taipei
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Novartis Pharmaceuticals
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
This is a phase Ib/II open label study. The escalation part will characterize the safety and tolerability of JDQ443 single agent and JDQ443 in combination with the other study treatments (TNO155 and tislelizumab) in advanced solid tumor patients. After the determination of the maximum tolerated dose / recommended dose for a particular treatment arm, dose expansion will assess the anti-tumor activity and further assess the safety, tolerability, and PK/PD of each regimen at the maximum tolerated dose / recommended dose or lower dose.
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Trial website
https://clinicaltrials.gov/study/NCT04699188
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Trial related presentations / publications
Lorthiois E, Gerspacher M, Beyer KS, Vaupel A, Leblanc C, Stringer R, Weiss A, Wilcken R, Guthy DA, Lingel A, Bomio-Confaglia C, Machauer R, Rigollier P, Ottl J, Arz D, Bernet P, Desjonqueres G, Dussauge S, Kazic-Legueux M, Lozac'h MA, Mura C, Sorge M, Todorov M, Warin N, Zink F, Voshol H, Zecri FJ, Sedrani RC, Ostermann N, Brachmann SM, Cotesta S. JDQ443, a Structurally Novel, Pyrazole-Based, Covalent Inhibitor of KRASG12C for the Treatment of Solid Tumors. J Med Chem. 2022 Dec 22;65(24):16173-16203. doi: 10.1021/acs.jmedchem.2c01438. Epub 2022 Nov 18.
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Public notes
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Contacts
Principal investigator
Name
0
0
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Address
0
0
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Country
0
0
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Phone
0
0
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Fax
0
0
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Email
0
0
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Contact person for public queries
Name
0
0
Novartis Pharmaceuticals
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Address
0
0
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Country
0
0
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Phone
0
0
1-888-669-6682
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Fax
0
0
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Email
0
0
[email protected]
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
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What data in particular will be shared?
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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When will data be available (start and end dates)?
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Available to whom?
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Available for what types of analyses?
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How or where can data be obtained?
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT04699188