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Locally Advanced or Metastatic KRAS G12C-mutated NSCLC With a PD-L1 Expression <1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutationPhase 2KontRASt-06NCT05445843

Study of Efficacy and Safety of JDQ443 Single-agent as First-line Treatment for Patients With Locally Advanced or Metastatic KRAS G12C- Mutated Non-small Cell Lung Cancer With a PD-L1 Expression < 1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation.

A Phase 2 study testing JDQ443 in people with Locally Advanced or Metastatic KRAS G12C-mutated NSCLC With a PD-L1 Expression <1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation, run by Novartis Pharmaceuticals at 45 sites in 19 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This study aims to evaluate the antitumor activity and safety of JDQ443 single-agent as first-line treatment for participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors harbor a KRAS G12C mutation and have a PD-L1 expression < 1% (cohort A) or a PD-L1 expression ≥ 1% and an… Read more about this study

Who is it for?
Ages 18 to 100 years
What is being tested?
JDQ443
Could I receive a placebo?
No, everyone receives an active treatment
How many people
95 participants
Where
45 sitesin 19 countries
Study dates
6 Dec 2022to 28 Oct 2026
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Histologically confirmed locally advanced (stage IIIb/IIIc not eligible for definitive chemoradiation or surgical resection with curative intent) or metastatic (stage IV) NSCLC without previous systemic treatment for metastatic disease. Prior (neo)adjuvant treatment with chemotherapy and/or immunotherapy, or prior radiotherapy administered sequentially or concomitantly with chemotherapy and/or immunotherapy for localized or locally advanced disease are accepted if the time between therapy completion and enrollment is > 12 months.
  • Presence of a KRAS G12C mutation (all participants) and:
  • Cohort A: PD-L1 expression < 1%, regardless of STK11 mutation status
  • Cohort B: PD-L1 expression ≥ 1% and an STK11 co-mutation
  • At least one measurable lesion per RECIST 1.1.
  • ECOG performance status ≤ 1.
  • Participants capable of swallowing study medication.

Who cannot join

  • Participants whose tumors harbor an EGFR-sensitizing mutation and/or ALK rearrangement by local laboratory testing. Participants with other known druggable alterations will be excluded, if required by local guidelines
  • Previous use of a KRAS G12C inhibitor or previous systemic treatment for metastatic NSCLC.
  • A medical condition that results in increased photosensitivity (i.e., solar urticaria, lupus erythematosus, etc.).
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Participants who are taking a prohibited medication (strong CYP3A inducers) that cannot be discontinued at least seven days prior to the first dose of study treatment and for the duration of the study.
  • Other inclusion/exclusion criteria may apply

Trial locations and contacts

45 sites in 19 countries.

45 sites in 19 countries

France5 sites
  • Novartis Investigative Site

    Bron, 69677

  • Novartis Investigative Site

    Marseille, Bouches Du Rhone, 13915

  • Novartis Investigative Site

    Montpellier, 34070

  • Novartis Investigative Site

    Saint-Herblain, 44805

  • Novartis Investigative Site

    Strasbourg, 67091

Other trials in France

Germany5 sites
  • Novartis Investigative Site

    Halle, Saxony-Anhalt, 06120

  • Novartis Investigative Site

    Hamburg, 21075

  • Novartis Investigative Site

    Kempten (Allgäu), Bavaria, 87439

  • Novartis Investigative Site

    Oldenburg, 26121

  • Novartis Investigative Site

    Tübingen, 72076

Other trials in Germany

Argentina4 sites
  • Novartis Investigative Site

    Buenos Aires, C1426AGE

  • Novartis Investigative Site

    Córdoba, Córdoba Province, X5016KEH

  • Novartis Investigative Site

    Córdoba, X5000JHQ

  • Novartis Investigative Site

    Pilar, Buenos Aires, B1629AHJ

Other trials in Argentina

Italy4 sites
  • Novartis Investigative Site

    Bari, BA, 70124

  • Novartis Investigative Site

    Orbassano, TO, 10043

  • Novartis Investigative Site

    Roma, RM, 00128

  • Novartis Investigative Site

    Rozzano, MI, 20089

Other trials in Italy

Brazil3 sites
  • Novartis Investigative Site

    Belo Horizonte, 30360-680

  • Novartis Investigative Site

    Rio de Janeiro, 22271-110

  • Novartis Investigative Site

    Salvador, Estado de Bahia, 40170-110

Other trials in Brazil

China3 sites
  • Novartis Investigative Site

    Beijing, 100036

  • Novartis Investigative Site

    Changsha, Hunan, 410013

  • Novartis Investigative Site

    Wuhan, Hubei, 430030

Other trials in China

Turkey (Türkiye)3 sites
  • Novartis Investigative Site

    Ankara, Yenimahalle, 06500

  • Novartis Investigative Site

    Diyarbakır, Sur, 21280

  • Novartis Investigative Site

    Istanbul, Bagcilar, 34214

Other trials in Turkey (Türkiye)

Austria2 sites
  • Novartis Investigative Site

    Feldkirch, 6807

  • Novartis Investigative Site

    Wels, 4600

Other trials in Austria

Belgium2 sites
  • Novartis Investigative Site

    Roeselare, West-Vlaanderen, 8800

  • Novartis Investigative Site

    Sint-Niklaas, Oost Vlaanderen, 9100

Other trials in Belgium

India2 sites
  • Novartis Investigative Site

    Thellakom Kottayam, Kerala, 686016

  • Novartis Investigative Site

    Varanasi, Uttar Pradesh, 221005

Other trials in India

Malaysia2 sites
  • Novartis Investigative Site

    George Town, Pulau Pinang, 10450

  • Novartis Investigative Site

    Kuching, Sarawak, 93586

Other trials in Malaysia

Netherlands2 sites
  • Novartis Investigative Site

    Breda, North Brabant, 4818 CK

  • Novartis Investigative Site

    Leeuwarden, Provincie Friesland, 8934 AD

Other trials in Netherlands

Spain2 sites
  • Novartis Investigative Site

    Barcelona, 08035

  • Novartis Investigative Site

    Madrid, 28041

Other trials in Spain

United States1 site
  • The Brown University Oncology Group

    Providence, Rhode Island, 02903

Other trials in United States

Greece1 site
  • Novartis Investigative Site

    Athens, 11526

Other trials in Greece

Hungary1 site
  • Novartis Investigative Site

    Mátraháza, 3200

Other trials in Hungary

Portugal1 site
  • Novartis Investigative Site

    Porto, 4100-180

Other trials in Portugal

Thailand1 site
  • Novartis Investigative Site

    Bangkok, 10700

Other trials in Thailand

United Kingdom1 site
  • Novartis Investigative Site

    Torquay, TQ2 7AA

Other trials in United Kingdom

About this study

Official title: KontRASt-06: An Open-label Phase II Trial Evaluating the Activity and Safety of JDQ443 Single-agent as First-line Treatment for Patients With Locally Advanced or Metastatic KRAS G12C-mutated Non-small Cell Lung Cancer With a PD-L1 Expression < 1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation.

This study aims to evaluate the antitumor activity and safety of JDQ443 single-agent as first-line treatment for participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors harbor a KRAS G12C mutation and have a PD-L1 expression < 1% (cohort A) or a PD-L1 expression ≥ 1% and an STK11 co-mutation (cohort B).

Read the detailed description

This is a non-randomized, open-label, single-arm, multicenter, phase II study evaluating the antitumor activity and safety of JDQ443 single-agent as first-line treatment for participants with locally advanced or metastatic KRAS G12C-mutated NSCLC.

The study will have 2 non-comparative cohorts that will recruit participants in parallel according to the following characteristics:

  • Cohort A: participants whose tumors harbor a KRAS G12C mutation and a PD-L1 expression < 1%, regardless of STK11 mutation status (N=90).
  • Cohort B: participants whose tumors harbor a KRAS G12C mutation, a PD-L1 expression ≥ 1% and an STK11 co-mutation (N=30).

The study treatment begins on Cycle 1 Day 1 (C1D1) with the first administration of JDQ443. One treatment cycle consists of 21 (±3) days.

Study completion is defined as the earliest occurrence of one of the following:

  • The last participant completes last study visit (and the assessments associated with this visit have been documented and followed-up appropriately by the Investigator), dies, withdraws consent, or is lost to follow-up, whichever comes first.]
  • In the event of an early study termination decision, the date of that decision.
  • Another clinical study becomes available that can continue to provide JDQ443 to study participants and all participants with ongoing treatment are transferred to that clinical study.
Being tested
JDQ443
Keywords
Lung cancer, NSCLC, KRAS G12C, STK11, PD-L1, JDQ443
Medical subject headings
Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • JDQ443Drug

    JDQ443 per os (PO) 200 mg twice a day continuously

Study groups in NCT05445843
Study groupRoleWhat they receive
Cohort A- PD-L1<1%ExperimentalParticipants whose tumors harbor a KRAS G12C mutation and a PD-L1 expression < 1%, regardless of STK11 mutation status.
Receives: Drug: JDQ443
Cohort B- PD-L1≥ 1% and STK11 mutationExperimentalParticipants whose tumors harbor a KRAS G12C mutation, a PD-L1 expression ≥ 1% and an STK11 co-mutation.
Receives: Drug: JDQ443

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (ORR) as Determined by the Investigator in Cohort A

    Overall Response Rate (ORR) was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) as best overall response (BOR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by the Investigator in Cohort A.

    Measured: Up to approximately 22 months

Secondary outcomes (12)
  1. Key Secondary Outcome Measure: Overall Response Rate (ORR) as Determined by the Investigator in Cohort B

    Overall Response Rate (ORR) was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) as best overall response (BOR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by the Investigator in Cohort B.

    Measured: Up to approximately 22 months

  2. Number of Adverse Events and Serious Adverse Events as Assessed by CTCAE Criteria

    The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs) and Serious Adverse Event (TESAEs), through the monitoring of relevant clinical and laboratory safety parameters.

    Treatment-emergent Adverse Events (TEAEs) in this study are defined as events that begin after the first dose of study treatment and continue until 30 days after the last dose of study treatment, or events that are present prior to the first dose of treatment and increase in severity based on preferred term within 30 days after the last study treatment.

    Measured: Up to approximately 59 months

  3. Plasma JDQ443 Concentration in All Participants

    JDQ443 concentration data of all participants were reported separately for each of the two cohorts and summarized using descriptive statistics.

    Measured: Cycle 1 Day 1 (predose/0hour, 4 hours and 6 hours), Cycle 1 Day 15 (predose/0hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours and 12 hours). Cycles 3, 5 and 7 Day 1 (predose/0hour). 1 cycle = 21 days.

  4. Plasma JDQ443 Concentration in Chinese Participants

    JDQ443 concentration data of Chinese participants were reported separately for each of the two cohorts and summarized using descriptive statistics.

    Measured: Cycle 1 Day 1 (predose/0hour, 4 hours and 6 hours), Cycle 1 Day 15 (predose/0hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours and 12 hours). Cycles 3, 5 and 7 Day 1 (predose/0hour). 1 cycle = 21 days.

  5. Plasma JDQ443 Concentration in Non-Chinese Participants

    JDQ443 concentration data of non-Chinese participants were reported separately for each of the two cohorts and summarized using descriptive statistics.

    Measured: Cycle 1 Day 1 (predose/0hour, 4 hours and 6 hours), Cycle 1 Day 15 (predose/0hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours and 12 hours). Cycles 3, 5 and 7 Day 1 (predose/0hour). 1 cycle = 21 days.

  6. Observed Maximum Plasma Concentration (Cmax) of JDQ443

    Pharmacokinetic (PK) parameters were calculated based on JDQ443 plasma concentrations and actual sampling time points. PK parameters were reported separately for all participants, non-Chinese participants, and Chinese participants in each of the two cohorts. Cmax was listed and summarized using descriptive statistics.

    Measured: Cycle 1 Day 1 (predose/0hour, 4 hours and 6 hours), Cycle 1 Day 15 (predose/0hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours and 12 hours). Cycles 3, 5 and 7 Day 1 (predose/0hour). 1 cycle = 21 days.

  7. Time to Reach Maximum Plasma Concentration (Tmax) of JDQ443

    Pharmacokinetic (PK) parameters were calculated based on JDQ443 plasma concentrations and actual sampling time points. PK parameters were reported separately for all participants, non-Chinese participants, and Chinese participants in each of the two cohorts. Tmax was listed and summarized using descriptive statistics.

    Measured: Cycle 1 Day 1 (predose/0hour, 4 hours and 6 hours), Cycle 1 Day 15 (predose/0hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours and 12 hours). Cycles 3, 5 and 7 Day 1 (predose/0hour). 1 cycle = 21 days.

  8. Time to Last Nonzero Plasma Concentration (Tlast) of JDQ443

    Pharmacokinetic (PK) parameters were calculated based on JDQ443 plasma concentrations and actual sampling time points. PK parameters were reported separately for all participants, non-Chinese participants, and Chinese participants in each of the two cohorts. Tlast was listed and summarized using descriptive statistics.

    Measured: Cycle 1 Day 1 (predose/0hour, 4 hours and 6 hours), Cycle 1 Day 15 (predose/0hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours and 12 hours). Cycles 3, 5 and 7 Day 1 (predose/0hour). 1 cycle = 21 days.

  9. Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of JDQ443

    Pharmacokinetic (PK) parameters were calculated based on JDQ443 plasma concentrations and actual sampling time points. PK parameters were reported separately for all participants, non-Chinese participants, and Chinese participants in each of the two cohorts. AUC∞ was listed and summarized using descriptive statistics.

    Measured: Cycle 1 Day 1 (predose/0hour, 4 hours and 6 hours), Cycle 1 Day 15 (predose/0hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours and 12 hours). Cycles 3, 5 and 7 Day 1 (predose/0hour). 1 cycle = 21 days.

  10. Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of JDQ443

    Pharmacokinetic (PK) parameters were calculated based on JDQ443 plasma concentrations and actual sampling time points. PK parameters were reported separately for all participants, non-Chinese participants, and Chinese participants in each of the two cohorts. AUClast was listed and summarized using descriptive statistics.

    Measured: Cycle 1 Day 1 (predose/0hour, 4 hours and 6 hours), Cycle 1 Day 15 (predose/0hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours and 12 hours). Cycles 3, 5 and 7 Day 1 (predose/0hour). 1 cycle = 21 days.

  11. Area Under the Plasma Concentration-time Curve During a Dosage Interval (AUCτ) of JDQ443

    Pharmacokinetic (PK) parameters were calculated based on JDQ443 plasma concentrations and actual sampling time points. PK parameters were reported separately for all participants, non-Chinese participants, and Chinese participants in each of the two cohorts. AUCτ was listed and summarized using descriptive statistics.

    Measured: Cycle 1 Day 1 (predose/0hour, 4 hours and 6 hours), Cycle 1 Day 15 (predose/0hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours and 12 hours). Cycles 3, 5 and 7 Day 1 (predose/0hour). 1 cycle = 21 days.

  12. Total Body Clearance (CL/F) of JDQ443 in Plasma

    Pharmacokinetic (PK) parameters were calculated based on JDQ443 plasma concentrations and actual sampling time points. PK parameters were reported separately for all participants, non-Chinese participants, and Chinese participants in each of the two cohorts. CL/F was listed and summarized using descriptive statistics.

    Measured: Cycle 1 Day 1 (predose/0hour, 4 hours and 6 hours), Cycle 1 Day 15 (predose/0hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours and 12 hours). Cycles 3, 5 and 7 Day 1 (predose/0hour). 1 cycle = 21 days.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jul 2022
  2. Study start6 Dec 2022
  3. Primary completion4 Nov 2024
  4. Study completion28 Oct 2026 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
95 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05445843
Sponsor's protocol ID
CJDQ443B12201
Other IDs
2024-511708-18-00
Acronym
KontRASt-06
Status last verified
Sep 2026
First submitted
30 Jun 2022
Last updated
8 Oct 2026
Data monitoring committee
No
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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing JDQ443 in people with Locally Advanced or Metastatic KRAS G12C-mutated NSCLC With a PD-L1 Expression <1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation, run by Novartis Pharmaceuticals at 45 sites in 19 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 7 inclusion and 6 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: under way, not looking for participants, as of the sponsor's last update on 8 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 45 sites in France, Germany, Argentina, Italy, Brazil and 14 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 phase mean?

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?

Yes. Results are posted in the registry (first posted 9 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Overall Response Rate (ORR) as Determined by the Investigator in Cohort A (time frame: Up to approximately 22 months). 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 8 Oct 2026.

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