Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT04699188
Registration number
NCT04699188
Ethics application status
Date submitted
5/01/2021
Date registered
7/01/2021
Date last updated
4/06/2024
Titles & IDs
Public title
Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation
Query!
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
Query!
Secondary ID [1]
0
0
2020-004129-22
Query!
Secondary ID [2]
0
0
CJDQ443A12101
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
KontRASt-01
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
KRAS G12C Mutant Solid Tumors
0
0
Query!
Carcinoma, Non-Small-Cell Lung
0
0
Query!
Carcinoma, Colorectal
0
0
Query!
Cancer of Lung
0
0
Query!
Cancer of the Lung
0
0
Query!
Lung Cancer
0
0
Query!
Neoplasms, Lung
0
0
Query!
Neoplasms, Pulmonary
0
0
Query!
Pulmonary Cancer
0
0
Query!
Pulmonary Neoplasms
0
0
Query!
Condition category
Condition code
Cancer
0
0
0
0
Query!
Non melanoma skin cancer
Query!
Cancer
0
0
0
0
Query!
Kidney
Query!
Cancer
0
0
0
0
Query!
Lung - Mesothelioma
Query!
Cancer
0
0
0
0
Query!
Lung - Non small cell
Query!
Cancer
0
0
0
0
Query!
Lung - Small cell
Query!
Cancer
0
0
0
0
Query!
Bowel - Back passage (rectum) or large bowel (colon)
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Drugs - JDQ443
Treatment: Drugs - TNO155
Other interventions - 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
Other interventions: tislelizumab
Anti PD1 antibody
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Intervention code [2]
0
0
Other interventions
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Dose Escalation: Incidence and severity of dose limiting toxicities (DLTs) during the first cycle of monotherapy or combination treatment
Query!
Assessment method [1]
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
Query!
Timepoint [1]
0
0
21 days
Query!
Primary outcome [2]
0
0
Dose Escalation: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
Query!
Assessment method [2]
0
0
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).
Query!
Timepoint [2]
0
0
24 months
Query!
Primary outcome [3]
0
0
Dose Escalation: Frequency of dose interruptions and reductions, by treatment
Query!
Assessment method [3]
0
0
Tolerability of study drug will be assessed by summarizing the number of and reason for dose delays and dose reductions.
Query!
Timepoint [3]
0
0
24 months
Query!
Primary outcome [4]
0
0
Dose Escalation: Dose intensity by treatment
Query!
Assessment method [4]
0
0
Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of treatment.
Query!
Timepoint [4]
0
0
24 months
Query!
Primary outcome [5]
0
0
Dose Expansion: Overall response rate (ORR) per RECIST v1.1, by treatment
Query!
Assessment method [5]
0
0
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.
Query!
Timepoint [5]
0
0
24 months
Query!
Primary outcome [6]
0
0
Dose expansion: Overall intracranial response rate (OIRR) per mRANO-BM
Query!
Assessment method [6]
0
0
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.
Query!
Timepoint [6]
0
0
24 months
Query!
Primary outcome [7]
0
0
Dose expansion: Incidence and severity of AEs and SAEs
Query!
Assessment method [7]
0
0
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.
Query!
Timepoint [7]
0
0
24 months
Query!
Primary outcome [8]
0
0
Dose expansion: frequency of dose interruptions and reductions, by treatment
Query!
Assessment method [8]
0
0
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.
Query!
Timepoint [8]
0
0
24 months
Query!
Primary outcome [9]
0
0
Dose expansion: Dose intensity by treatment
Query!
Assessment method [9]
0
0
Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of treatment. Applies to JDQ443 dose randomization group only
Query!
Timepoint [9]
0
0
24 months
Query!
Primary outcome [10]
0
0
Dose expansion: ORR per RECIST 1.1 of JDQ443 single agent in patients with non-small cell lung cancer (JDQ443 dose randomization group only)
Query!
Assessment method [10]
0
0
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
Query!
Timepoint [10]
0
0
24 months
Query!
Secondary outcome [1]
0
0
Dose Escalation and Expansion: ORR per RECIST v1.1
Query!
Assessment method [1]
0
0
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)
Query!
Timepoint [1]
0
0
24 months
Query!
Secondary outcome [2]
0
0
Dose Escalation and Expansion: Best Overall Response (BOR) per RECIST v1.1
Query!
Assessment method [2]
0
0
BOR is defined as the best overall confirmed response recorded from the start of the treatment until disease progression/recurrence.
Query!
Timepoint [2]
0
0
24 months
Query!
Secondary outcome [3]
0
0
Dose Escalation and Expansion: Progression-free survival (PFS) per RECIST v1.1, Overall Survival (OS)
Query!
Assessment method [3]
0
0
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
Query!
Timepoint [3]
0
0
24 months
Query!
Secondary outcome [4]
0
0
Dose Escalation and Expansion: Duration of Response (DOR) per RECIST v1.1
Query!
Assessment method [4]
0
0
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.
Query!
Timepoint [4]
0
0
24 months
Query!
Secondary outcome [5]
0
0
Dose Escalation and Expansion: Disease Control Rate (DCR) per RECIST v1.1
Query!
Assessment method [5]
0
0
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
Query!
Timepoint [5]
0
0
24 months
Query!
Secondary outcome [6]
0
0
Dose Escalation and Expansion: Plasma or serum concentration vs time profiles (AUC) by treatment
Query!
Assessment method [6]
0
0
AUC is defined as area under the plasma or serum concentration versus time curve after a dose of JDQ443, TNO155 and tislelizumab
Query!
Timepoint [6]
0
0
Up to 24 months
Query!
Secondary outcome [7]
0
0
Dose Escalation and Expansion: Plasma concentration (Cmax) by treatment
Query!
Assessment method [7]
0
0
Cmax is defined as the maximum observed plasma or serum drug concentration after single dose administration.
Query!
Timepoint [7]
0
0
Up to 24 months
Query!
Secondary outcome [8]
0
0
Dose Escalation and Expansion: Time to achieve Cmax (Tmax) by treatment
Query!
Assessment method [8]
0
0
Tmax is defined as the time to reach maximum plasma or serum drug concentration after single dose administration.
Query!
Timepoint [8]
0
0
Up to 24 months
Query!
Secondary outcome [9]
0
0
Dose Escalation and Expansion: Antidrug antibody (ADA) incidence by treatment
Query!
Assessment method [9]
0
0
To evaluate the immunogenicity of tislelizumab when dosed in combination with JDQ443 and/or TNO155 - only applicable to Arms C and D
Query!
Timepoint [9]
0
0
Up to 24 months
Query!
Secondary outcome [10]
0
0
Dose Expansion: Dose intensity by treatment
Query!
Assessment method [10]
0
0
Query!
Timepoint [10]
0
0
24 months
Query!
Secondary outcome [11]
0
0
Dose Expansion: Frequency of dose interruptions and reductions, by treatment
Query!
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.
Query!
Timepoint [11]
0
0
24 months
Query!
Secondary outcome [12]
0
0
Dose Expansion: Incidence and severity of dose limiting toxicities (DLTs) during the first cycle of monotherapy or combination treatment
Query!
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
Query!
Timepoint [12]
0
0
21 days
Query!
Secondary outcome [13]
0
0
Dose Expansion: Incidence and severity of AEs and SAEs by treatment
Query!
Assessment method [13]
0
0
Query!
Timepoint [13]
0
0
24 months
Query!
Secondary outcome [14]
0
0
Dose expansion: Intracranial disease control rate (IDCR) per mRANO-BM
Query!
Assessment method [14]
0
0
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.
Query!
Timepoint [14]
0
0
24 months
Query!
Secondary outcome [15]
0
0
Dose expansion: Best overall intracranial response (BOIR) per mRANO-BM
Query!
Assessment method [15]
0
0
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.
Query!
Timepoint [15]
0
0
24 months
Query!
Secondary outcome [16]
0
0
Dose expansion: Intracranial progression free survival (IPFS) per mRANO-BM
Query!
Assessment method [16]
0
0
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.
Query!
Timepoint [16]
0
0
24 months
Query!
Secondary outcome [17]
0
0
Dose expansion: Duration of intracranial response (DOIR) per mRANO-BM
Query!
Assessment method [17]
0
0
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.
Query!
Timepoint [17]
0
0
24 months
Query!
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
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
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.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Non-randomised trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 1/Phase 2
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Recruiting
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
24/02/2021
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
8/01/2027
Query!
Actual
Query!
Sample size
Target
475
Query!
Accrual to date
Query!
Final
Query!
Recruitment in Australia
Recruitment state(s)
VIC
Query!
Recruitment hospital [1]
0
0
Novartis Investigative Site - Melbourne
Query!
Recruitment postcode(s) [1]
0
0
3000 - Melbourne
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
Georgia
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Massachusetts
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Missouri
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Oregon
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Pennsylvania
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Texas
Query!
Country [7]
0
0
Belgium
Query!
State/province [7]
0
0
Leuven
Query!
Country [8]
0
0
Canada
Query!
State/province [8]
0
0
Quebec
Query!
Country [9]
0
0
China
Query!
State/province [9]
0
0
Fujian
Query!
Country [10]
0
0
China
Query!
State/province [10]
0
0
Guangdong
Query!
Country [11]
0
0
China
Query!
State/province [11]
0
0
Jiangxi
Query!
Country [12]
0
0
China
Query!
State/province [12]
0
0
Beijing
Query!
Country [13]
0
0
Denmark
Query!
State/province [13]
0
0
Copenhagen
Query!
Country [14]
0
0
France
Query!
State/province [14]
0
0
Lyon
Query!
Country [15]
0
0
France
Query!
State/province [15]
0
0
Marseille
Query!
Country [16]
0
0
France
Query!
State/province [16]
0
0
Villejuif
Query!
Country [17]
0
0
Germany
Query!
State/province [17]
0
0
Dresden
Query!
Country [18]
0
0
Germany
Query!
State/province [18]
0
0
Essen
Query!
Country [19]
0
0
Germany
Query!
State/province [19]
0
0
Freiburg
Query!
Country [20]
0
0
Germany
Query!
State/province [20]
0
0
Koeln
Query!
Country [21]
0
0
Hong Kong
Query!
State/province [21]
0
0
Hong Kong
Query!
Country [22]
0
0
Italy
Query!
State/province [22]
0
0
BS
Query!
Country [23]
0
0
Italy
Query!
State/province [23]
0
0
MI
Query!
Country [24]
0
0
Japan
Query!
State/province [24]
0
0
Aichi
Query!
Country [25]
0
0
Japan
Query!
State/province [25]
0
0
Chiba
Query!
Country [26]
0
0
Japan
Query!
State/province [26]
0
0
Kanagawa
Query!
Country [27]
0
0
Japan
Query!
State/province [27]
0
0
Osaka
Query!
Country [28]
0
0
Japan
Query!
State/province [28]
0
0
Tokyo
Query!
Country [29]
0
0
Korea, Republic of
Query!
State/province [29]
0
0
Seoul
Query!
Country [30]
0
0
Netherlands
Query!
State/province [30]
0
0
Amsterdam
Query!
Country [31]
0
0
Singapore
Query!
State/province [31]
0
0
Singapore
Query!
Country [32]
0
0
Spain
Query!
State/province [32]
0
0
Andalucia
Query!
Country [33]
0
0
Spain
Query!
State/province [33]
0
0
Catalunya
Query!
Country [34]
0
0
Spain
Query!
State/province [34]
0
0
Comunidad Valenciana
Query!
Country [35]
0
0
Spain
Query!
State/province [35]
0
0
Galicia
Query!
Country [36]
0
0
Spain
Query!
State/province [36]
0
0
Madrid
Query!
Country [37]
0
0
Taiwan
Query!
State/province [37]
0
0
Tainan
Query!
Country [38]
0
0
Taiwan
Query!
State/province [38]
0
0
Taipei
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
Novartis Pharmaceuticals
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
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.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT04699188
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Novartis Pharmaceuticals
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
1-888-669-6682
Query!
Fax
0
0
Query!
Email
0
0
[email protected]
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04699188
Download to PDF