KRAS G12C Mutant Solid TumorsPhase 1/2KontRASt-03NCT05358249
Platform Study of JDQ443 in Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation
A Phase 1/2 study testing JDQ443, trametinib and Ribociclib in people with KRAS G12C Mutant Solid Tumors and Carcinoma, Non-Small Cell Lung, run by Novartis Pharmaceuticals at 13 sites in 8 countries.
Trial summary
This was Phase Ib/II, multicenter, open-label adaptive platform study of JDQ443 with select therapies in patients with advanced solid tumors harboring the KRAS G12C mutation. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- KRAS G12C Mutant Solid Tumors, Carcinoma, Non-Small Cell Lung, Carcinoma, Non-Small-Cell Lung
- What is being tested?
- JDQ443, trametinib and Ribociclib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 13 sitesin 8 countries
- Study dates
- 24 Oct 2022to 28 Sep 2026
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Dose Escalation:
- Patients with advanced (metastatic or unresectable) KRAS G12C mutant solid tumors who have received standard of care therapy or are ineligible to receive such therapy.
- Phase II:
- Patients with advanced (metastatic or unresectable) KRAS G12C mutant non-small cell lung cancer who have received platinum-based chemotherapy regimen and immune checkpoint inhibitor therapy, unless patient was ineligible to receive such therapy
- Patients with advanced (metastatic or unresectable) KRAS G12C mutant colorectal cancer who have received fluropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, unless patient was ineligible to such therapy.
- All patients:
- ECOG performance status of 0 or 1.
- Patients must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the treating institution's guidelines.
Who cannot join
- Tumors harboring driver mutations that have approved targeted therapies, with the exception of KRAS G12C mutations
- Prior treatment with a KRAS G12C inhibitor is excluded for patients in a subset of groups in Phase II.
- Active brain metastases, including symptomatic brain metastases or known leptomeningeal disease
- Clinically significant cardiac disease or risk factors at screening
- Insufficient bone marrow, hepatic or renal function at screening Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
13 sites in 8 countries.
13 sites in 8 countries
United States3 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
NYU School of Medicine
New York, New York, 10015
Spain3 sites
Novartis Investigative Site
Barcelona, 08036
Novartis Investigative Site
Madrid, 28034
Novartis Investigative Site
Madrid, 28050
France2 sites
Novartis Investigative Site
Bordeaux, 33076
Novartis Investigative Site
Lyon, 69373
Germany1 site
Novartis Investigative Site
Freiburg im Breisgau, Baden-Wurttemberg, 79106
About this study
Official title: KontRASt-03: A Phase Ib/II, Multicenter, Open-label Platform Study of JDQ443 With Select Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation
This was Phase Ib/II, multicenter, open-label adaptive platform study of JDQ443 with select therapies in patients with advanced solid tumors harboring the KRAS G12C mutation.
Read the detailed description
JDQ443 was considered "backbone" treatment in this trial and combined with selected therapies, or "partner(s)". The combination of a backbone and a partner constituted a treatment arm. After dose escalation, treatment arms that reached a maximum tolerated dose /recommended dose and were determined to be safe could, but were not required to, proceed to Phase II to further explore safety, tolerability, and anti-tumor activity.
- Conditions
- KRAS G12C Mutant Solid Tumors, Carcinoma, Non-Small Cell Lung, Carcinoma, Non-Small-Cell Lung, Non-Small Cell Lung Cancer, Non-Small Cell Lung Carcinoma, Nonsmall Cell Lung Cancer
- Being tested
- JDQ443, trametinib, Ribociclib, cetuximab
- Keywords
- KRAS G12C, targeted therapy, NSCLC, CRC, advanced solid tumors, JDQ443, trametinib, ribociclib, cetuximab
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JDQ443Drug
KRAS G12C inhibitor, oral
trametinibDrug
Also called TMT212
MEK inhibitor, oral
RibociclibDrug
Also called LEE011
CDK4/6 inhibitor, oral
cetuximabBiological
EGFR inhibitor, intravenous
| Study group | Role | What they receive |
|---|---|---|
| JDQ443+trametinib | Experimental | JDQ443 in combination with trametinib Receives: Drug: JDQ443; Drug: trametinib |
| JDQ443+ribociclib | Experimental | JDQ443 in combination with ribociclib Receives: Drug: JDQ443; Drug: Ribociclib |
| JDQ443+cetuximab | Experimental | JDQ443 in combination with cetuximab Receives: Drug: JDQ443; Biological: cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose escalation: Incidence and severity of dose limiting toxicities (DLTs) of each combination treatment.
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value that is not primarily related to disease, disease progression, intercurrent illness/injury, or concomitant medications that occurs within the first 28 days of study treatment and meets a defined criteria.
Measured: 28 days
Dose escalation: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) by treatment
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).
Measured: 24 months
Dose escalation: Frequency of dose interruptions and reductions, by treatment
The number of patients with dose adjustments (reductions and interruptions) will be summarized by treatment group.
Measured: 24 months
Dose Escalation: Dose intensity by treatment
Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of response.
Measured: 24 months
PhaseII: Overall Response Rate by Blinded Independent Review Committee (BIRC) per RECIST 1.1
ORR is the proportion of patients with a best overall response (BOR) of Complete Response (CR) or Partial Response (PR).
Measured: 24 months
Secondary outcomes (16)
Dose escalation and Phase II: ORR by local review per RECIST 1.1
ORR is the proportion of patients with a BOR of CR or PR.
Measured: 24 months
Dose escalation and Phase II: Disease Control Rate (DCR) by local review per RECIST 1.1
DCR is the proportion of patients with a BOR of CR or PR or Stable Disease (SD). The objective of this endpoint is to summarize patients with signs of "activity" defined as either shrinkage of tumor (regardless of duration) or slowing down of tumor growth.
Measured: 24 months
Dose escalation and Phase II: Duration of Response (DoR) by local review per RECIST 1.1
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.
Measured: 24 months
Dose escalation and Phase II: Progression-Free Survival (PFS) by local review 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 due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.
Measured: 24 months
Phase II: DCR by BIRC per RECIST 1.1
DCR is the proportion of patients with a BOR of CR or PR or SD. The objective of this endpoint is to summarize patients with signs of "activity" defined as either shrinkage of tumor (regardless of duration) or slowing down of tumor growth.
Measured: 24 months
Phase II: DoR by BIRC per RECIST 1.1
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.
Measured: 24 months
Phase II: PFS by BIRC 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 due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.
Measured: 24 months
Phase II: Overall survival (OS)
OS is defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last known date patient alive.
Measured: 24 months
Dose escalation and Phase II: PK parameters - Maximum Concentration (Cmax), as applicable per arm
The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1)
Measured: 5 months
Dose escalation and Phase II: PK parameters - Minimum Concentration (Cmin), as applicable per arm
Observed concentration at the end of a dosing interval (taken directly before next administration)
Measured: 5 months
Dose escalation: Time to achieve Cmax - Tmax, as applicable per arm
The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time)
Measured: 5 months
Dose escalation and Phase II: Plasma or serum concentration vs time profiles - AUCtau, as applicable per arm
The Area under curve calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1)
Measured: 5 months
Dose escalation and Phase II: Plasma or serum concentration vs time profiles - AUCinf, as applicable per arm
The AUC from time zero to infinity (mass x time x volume-1)
Measured: 5 months
Phase II: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) by treatment
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).
Measured: 24 months
Phase II: Frequency of dose interruptions and reductions, by treatment
The number of patients with dose adjustments (reductions and interruptions) will be summarized by treatment group.
Measured: 24 months
Phase II: Dose intensity by treatment
Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of response.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2022
- Study start24 Oct 2022
- Primary completion28 Sep 2026
- Study completion28 Sep 2026
Why it stopped: Business reasons and not based on any safety concerns.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for KRAS G12C Mutant Solid TumorsStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05358249
- Sponsor's protocol ID
- CJDQ443E12101
- Other IDs
- 2021-006196-42, 2023-506716-41-00, 2023
- Acronym
- KontRASt-03
- Status last verified
- Oct 2026
- First submitted
- 27 Apr 2022
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- KontRASt-03: A Phase Ib/II, Multicenter, Open-label Platform Study of JDQ443 With Select Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation
- ClinicalTrials.gov ID
- NCT05358249
- Acronym / sponsor ID
- KontRASt-03 / CJDQ443E12101
- Conditions
- KRAS G12C Mutant Solid Tumors, Carcinoma, Non-Small Cell Lung, Carcinoma, Non-Small-Cell Lung, Non-Small Cell Lung Cancer, Non-Small Cell Lung Carcinoma, Nonsmall Cell Lung Cancer
- Keywords
- KRAS G12C, targeted therapy, NSCLC, CRC, advanced solid tumors, JDQ443, trametinib, ribociclib
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business reasons and not based on any safety concerns.
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 24 Oct 2022 (actual)
- Primary completion
- 28 Sep 2026 (actual)
- Study completion
- 28 Sep 2026 (actual)
- First posted
- 3 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was Phase Ib/II, multicenter, open-label adaptive platform study of JDQ443 with select therapies in patients with advanced solid tumors harboring the KRAS G12C mutation.
Detailed description
JDQ443 was considered "backbone" treatment in this trial and combined with selected therapies, or "partner(s)". The combination of a backbone and a partner constituted a treatment arm. After dose escalation, treatment arms that reached a maximum tolerated dose /recommended dose and were determined to be safe could, but were not required to, proceed to Phase II to further explore safety, tolerability, and anti-tumor activity.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| JDQ443+trametinib | Experimental | Drug: JDQ443, Drug: trametinibJDQ443 in combination with trametinib |
| JDQ443+ribociclib | Experimental | Drug: JDQ443, Drug: RibociclibJDQ443 in combination with ribociclib |
| JDQ443+cetuximab | Experimental | Drug: JDQ443, Biological: cetuximabJDQ443 in combination with cetuximab |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients with advanced (metastatic or unresectable) KRAS G12C mutant solid tumors who have received standard of care therapy or are ineligible to receive such therapy.
- Patients with advanced (metastatic or unresectable) KRAS G12C mutant non-small cell lung cancer who have received platinum-based chemotherapy regimen and immune checkpoint inhibitor therapy, unless patient was ineligible to receive such therapy
- Patients with advanced (metastatic or unresectable) KRAS G12C mutant colorectal cancer who have received fluropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, unless patient was ineligible to such therapy.
- ECOG performance status of 0 or 1.
- Patients must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the treating institution's guidelines.
Key exclusion criteria (5 listed)
- Tumors harboring driver mutations that have approved targeted therapies, with the exception of KRAS G12C mutations
- Prior treatment with a KRAS G12C inhibitor is excluded for patients in a subset of groups in Phase II.
- Active brain metastases, including symptomatic brain metastases or known leptomeningeal disease
- Clinically significant cardiac disease or risk factors at screening
- Insufficient bone marrow, hepatic or renal function at screening Other protocol-defined inclusion/exclusion criteria may apply
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| JDQ443KRAS G12C inhibitor, oral | Drug | JDQ443+cetuximab, JDQ443+ribociclib, JDQ443+trametinib |
| trametinibAlso: TMT212MEK inhibitor, oral | Drug | JDQ443+trametinib |
| RibociclibAlso: LEE011CDK4/6 inhibitor, oral | Drug | JDQ443+ribociclib |
| cetuximabEGFR inhibitor, intravenous | Biological | JDQ443+cetuximab |
Primary outcome
Dose escalation: Incidence and severity of dose limiting toxicities (DLTs) of each combination treatment.
Time frame: 28 days
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value that is not primarily related to disease, disease progression, intercurrent illness/injury, or concomitant medications that occurs within the first 28 days of study treatment and meets a defined criteria.
Dose escalation: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) by treatment
Time frame: 24 months
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).
Dose escalation: Frequency of dose interruptions and reductions, by treatment
Time frame: 24 months
The number of patients with dose adjustments (reductions and interruptions) will be summarized by treatment group.
Dose Escalation: Dose intensity by treatment
Time frame: 24 months
Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of response.
PhaseII: Overall Response Rate by Blinded Independent Review Committee (BIRC) per RECIST 1.1
Time frame: 24 months
ORR is the proportion of patients with a best overall response (BOR) of Complete Response (CR) or Partial Response (PR).
16 secondary outcomes
Dose escalation and Phase II: ORR by local review per RECIST 1.1
Time frame: 24 months
Dose escalation and Phase II: Disease Control Rate (DCR) by local review per RECIST 1.1
Time frame: 24 months
Dose escalation and Phase II: Duration of Response (DoR) by local review per RECIST 1.1
Time frame: 24 months
Dose escalation and Phase II: Progression-Free Survival (PFS) by local review per RECIST 1.1
Time frame: 24 months
Phase II: DCR by BIRC per RECIST 1.1
Time frame: 24 months
Phase II: DoR by BIRC per RECIST 1.1
Time frame: 24 months
Phase II: PFS by BIRC per RECIST 1.1
Time frame: 24 months
Phase II: Overall survival (OS)
Time frame: 24 months
Dose escalation and Phase II: PK parameters - Maximum Concentration (Cmax), as applicable per arm
Time frame: 5 months
Dose escalation and Phase II: PK parameters - Minimum Concentration (Cmin), as applicable per arm
Time frame: 5 months
Dose escalation: Time to achieve Cmax - Tmax, as applicable per arm
Time frame: 5 months
Dose escalation and Phase II: Plasma or serum concentration vs time profiles - AUCtau, as applicable per arm
Time frame: 5 months
Dose escalation and Phase II: Plasma or serum concentration vs time profiles - AUCinf, as applicable per arm
Time frame: 5 months
Phase II: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) by treatment
Time frame: 24 months
Phase II: Frequency of dose interruptions and reductions, by treatment
Time frame: 24 months
Phase II: Dose intensity by treatment
Time frame: 24 months
Results and safety
The study was stopped early (reason given: Business reasons and not based on any safety concerns.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2026.
- Individual participant dataSharing planned: Yes. 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
13 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing JDQ443, trametinib and Ribociclib in people with KRAS G12C Mutant Solid Tumors and Carcinoma, Non-Small Cell Lung, run by Novartis Pharmaceuticals at 13 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Spain, France, Belgium, Germany and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Business reasons and not based on any safety concerns.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose escalation: Incidence and severity of dose limiting toxicities (DLTs) of each combination treatment. (time frame: 28 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2026.