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. (KontRASt-06)

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).

Study Overview

• Status: Active, not recruiting
• Conditions: 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
• Intervention / Treatment: Drug: JDQ443

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.

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1426AGE
    • Novartis Investigative Site
  • Córdoba, Argentina, X5000JHQ
    • Novartis Investigative Site
  • Córdoba, Argentina, X5016KEH
    • Novartis Investigative Site
  • Buenos Aires
    • Pilar, Buenos Aires, Argentina, B1629AHJ
      • Novartis Investigative Site
• Austria
  • Feldkirch, Austria, A 6807
    • Novartis Investigative Site
  • Wels, Austria, A-4600
    • Novartis Investigative Site
• Belgium
  • Oost Vlaanderen
    • Sint-Niklaas, Oost Vlaanderen, Belgium, 9100
      • Novartis Investigative Site
  • West-Vlaanderen
    • Roeselare, West-Vlaanderen, Belgium, 8800
      • Novartis Investigative Site
• Brazil
  • Belo Horizonte, Brazil, 30360 680
    • Novartis Investigative Site
  • Rio de Janeiro, Brazil, 22271-110
    • Novartis Investigative Site
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 41825-010
      • Novartis Investigative Site
• China
  • Beijing, China, 100036
    • Novartis Investigative Site
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Novartis Investigative Site
  • Hunan
    • Changsha, Hunan, China, 410013
      • Novartis Investigative Site
• France
  • Bron, France, 69677
    • Novartis Investigative Site
  • Montpellier, France, 34070
    • Novartis Investigative Site
  • Saint-Herblain, France, 44805
    • Novartis Investigative Site
  • Strasbourg, France, 67091
    • Novartis Investigative Site
  • Bouches Du Rhone
    • Marseille, Bouches Du Rhone, France, 13915
      • Novartis Investigative Site
• Germany
  • Hamburg, Germany, 21075
    • Novartis Investigative Site
  • Oldenburg, Germany, 26121
    • Novartis Investigative Site
  • Tübingen, Germany, 72076
    • Novartis Investigative Site
  • Bavaria
    • Kempten (Allgäu), Bavaria, Germany, 87439
      • Novartis Investigative Site
  • Saxony-Anhalt
    • Halle, Saxony-Anhalt, Germany, 06120
      • Novartis Investigative Site
• Greece
  • Athens, Greece, 11526
    • Novartis Investigative Site
• Hungary
  • Mátraháza, Hungary, 3200
    • Novartis Investigative Site
• India
  • Kerala
    • Thellakom Kottayam, Kerala, India, 686016
      • Novartis Investigative Site
  • Uttar Pradesh
    • Varanasi, Uttar Pradesh, India, 221005
      • Novartis Investigative Site
• Italy
  • BA
    • Bari, BA, Italy, 70124
      • Novartis Investigative Site
  • MI
    • Rozzano, MI, Italy, 20089
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00128
      • Novartis Investigative Site
  • TO
    • Orbassano, TO, Italy, 10043
      • Novartis Investigative Site
• Malaysia
  • Pulau Pinang
    • George Town, Pulau Pinang, Malaysia, 10450
      • Novartis Investigative Site
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Novartis Investigative Site
• Netherlands
  • North Brabant
    • Breda, North Brabant, Netherlands, 4818 CK
      • Novartis Investigative Site
  • Provincie Friesland
    • Leeuwarden, Provincie Friesland, Netherlands, 8934 AD
      • Novartis Investigative Site
• Portugal
  • Porto, Portugal, 4100-180
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08035
    • Novartis Investigative Site
  • Madrid, Spain, 28041
    • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10700
    • Novartis Investigative Site
• Turkey (Türkiye)
  • Bagcilar
    • Istanbul, Bagcilar, Turkey (Türkiye), 34214
      • Novartis Investigative Site
  • Sur
    • Diyarbakır, Sur, Turkey (Türkiye), 21280
      • Novartis Investigative Site
  • Yenimahalle
    • Ankara, Yenimahalle, Turkey (Türkiye), 06500
      • Novartis Investigative Site
• United Kingdom
  • Torquay, United Kingdom, TQ2 7AA
    • Novartis Investigative Site
• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • The Brown University Oncology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion criteria

• 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.

Key Exclusion criteria

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort B- PD-L1≥ 1% and STK11 mutation; Participants whose tumors harbor a KRAS G12C mutation, a PD-L1 expression ≥ 1% and an STK11 co-mutation.	Drug: JDQ443; JDQ443 per os (PO) 200 mg twice a day continuously
Experimental: Cohort A- PD-L1<1%; Participants whose tumors harbor a KRAS G12C mutation and a PD-L1 expression < 1%, regardless of STK11 mutation status.	Drug: JDQ443; JDQ443 per os (PO) 200 mg twice a day continuously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to approximately 22 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to approximately 22 months
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.	Up to approximately 59 months
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.	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.
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.	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.
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.	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.
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.	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.
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.	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.
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.	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.
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.	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.
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.	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.
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.	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.
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.	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.

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2022
• Primary Completion (Actual): November 4, 2024
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: June 30, 2022
• First Submitted That Met QC Criteria: June 30, 2022
• First Posted (Actual): July 6, 2022

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; Lung cancer; PD-L1; KRAS G12C; STK11; JDQ443
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; JDQ443
• Other Study ID Numbers: CJDQ443B12201; 2024-511708-18-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No