Skip to main content
OpenTrials
Active, Not Recruiting

NCT Number: NCT05445843

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.

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).

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Notify Me

Key information

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 Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year–100 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Novartis Investigative Site, Pilar, Buenos Aires, Argentina

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

JDQ443

Drug

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

Primary outcomes

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

    Time frame: Up to approximately 22 months

    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.

Secondary outcomes

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

    Time frame: Up to approximately 22 months

    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.

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

    Time frame: Up to approximately 59 months

    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.

  3. Plasma JDQ443 Concentration in All Participants

    Time frame: 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.

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

  4. Plasma JDQ443 Concentration in Chinese Participants

    Time frame: 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.

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

  5. Plasma JDQ443 Concentration in Non-Chinese Participants

    Time frame: 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.

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

  6. Observed Maximum Plasma Concentration (Cmax) of JDQ443

    Time frame: 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.

    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.

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

    Time frame: 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.

    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.

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

    Time frame: 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.

    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.

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

    Time frame: 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.

    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.

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

    Time frame: 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.

    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.

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

    Time frame: 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.

    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.

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

    Time frame: 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.

    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.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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.

Acronym: KontRASt-06

Important dates

Study start
2022
Primary completion
2024
Study completion
2026
First posted
Jul 6, 2022
Registry last updated
Jul 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.