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Study of JDQ443 in Comparison With Docetaxel in Participants With Locally Advanced or Metastatic KRAS G12C Mutant Non-small Cell Lung Cancer (KontRASt-02)

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ClinicalTrials.gov Identifier: NCT05132075
Recruitment Status : Recruiting
First Posted : November 24, 2021
Last Update Posted : May 7, 2024
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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Brief Summary:
This is a phase III randomized open label study designed to compare JDQ443 as monotherapy to docetaxel in participants with advanced non-small cell lung cancer (NSCLC) harboring a KRAS G12C mutation who have been previously treated with a platinum-based chemotherapy and immune checkpoint inhibitor therapy either in sequence or in combination.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: JDQ443 Drug: docetaxel Phase 3

Detailed Description:

The study has been designed as a Phase III trial and consists of 2 parts:

  • Randomized part will evaluate the efficacy and safety of JDQ443 as monotherapy in comparison with docetaxel. Participants randomized to docetaxel arm will have the opportunity to cross-over to JDQ443 at disease progression per RECIST 1.1 confirmed by BIRC.
  • Extension part will be open after final progression-free survival (PFS) analysis (if the primary endpoint has met statistical significance) to allow participants randomized to docetaxel treatment to crossover to receive JDQ443 treatment regardless of progression on docetaxel.

The study population will include adult participants with locally advanced or metastatic (stage IIIB/IIIC or IV) KRAS G12C mutant non-small cell lung cancer (by tissue or plasma as determined by a Novartis-designated central laboratory or accepted local tests) who have received prior platinum-based chemotherapy and prior immune checkpoint inhibitor therapy administered either in sequence or as combination therapy.

Approximately 360 participants will be randomized to JDQ443 or docetaxel in a 1:1 ratio stratified by prior line of therapy and ECOG performance status.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 360 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Controlled, Open Label, Phase III Study Evaluating the Efficacy and Safety of JDQ443 Versus Docetaxel in Previously Treated Subjects With Locally Advanced or Metastatic KRAS G12C Mutant Non-small Cell Lung Cancer
Actual Study Start Date : June 15, 2022
Estimated Primary Completion Date : April 21, 2025
Estimated Study Completion Date : December 31, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Docetaxel

Arms and Interventions
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Arm Intervention/treatment
Experimental: JDQ443
Participants will be treated with JDQ443
 Drug: JDQ443
JDQ443 tablets, orally administered
Active Comparator: Docetaxel
Participant will be treated with docetaxel following local guidelines as per standard of care and product labels
 Drug: docetaxel
docetaxel concentrated solution for infusion, intravenously administered


Outcome Measures
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Primary Outcome Measures :
  1. Progression free survival (PFS) [ Time Frame: Approximately up to 24 months ]
    PFS is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is based on central assessment and using RECIST 1.1 criteria.


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Approximately up to 33 months ]
    OS is defined as the time from date of randomization to date of death due to any cause

  2. Overall Response Rate (ORR) [ Time Frame: Approximately up to 33 months ]
    ORR is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) based on central and local investigator's assessment according to RECIST 1.1.

  3. Disease Control Rate (DCR) [ Time Frame: Approximately up to 33 months ]
    DCR is defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Non-CR/Non-PD.

  4. Time To Response (TTR) [ Time Frame: Approximately up to 33 months ]
    TTR is defined as the time from the date of randomization to the date of first documented response (CR or PR, which must be confirmed subsequently)

  5. Duration of Response (DOR) [ Time Frame: Approximately up to 33 months ]
    DOR is calculated as the time from the date of first documented response (complete response (CR) or partial response (PR)) to the first documented date of progression or death due to underlying cancer.

  6. Progression-Free Survival after next line therapy (PFS2) [ Time Frame: Approximately up to 33 months ]
    PFS2 (based on local investigator assessment) is defined as time from date of randomization to the first documented progression on next line therapy or death from any cause, whichever occurs first.

  7. Concentration of JDQ443 and its metabolite in plasma [ Time Frame: Approximately up to 33 months ]
    To characterize the pharmacokinetics of JDQ443 and its metabolite HZC320

  8. Time to definitive deterioration of Eastern Cooperative Group of Oncology Group (ECOG) performance status [ Time Frame: Approximately up to 33 months ]
    Deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)

  9. Time to definitive 10-point deterioration symptom scores of chest pain, cough and dyspnea per QLQ-LC13 [ Time Frame: Approximately up to 33 months ]
    The EORTC QLQ LC13 is a 13-item, lung cancer specific questionnaire module, and it comprises both multi-item and single-item measures of lung cancer-associated symptoms (i.e. coughing, hemoptysis, dyspnea and pain) and side-effects from conventional chemo- and radiotherapy (i.e. hair loss, neuropathy, sore mouth and dysphagia). The time to definitive 10-point deterioration is defined as the time from the date of randomization to the date of event, which is defined as at least 10 points absolute increase from baseline (worsening), with no later change below the threshold or death due to any cause

  10. Time to definitive 10-point deterioration in global health status/QoL, shortness of breath and pain per QLQ-C30 [ Time Frame: Approximately up to 33 months ]
    The EORTC QLQ-C30 is a questionnaire developed to assess the health-related quality of life of cancer participants. The questionnaire contains 30 items and is composed of both multi-item scales and single-item measures based on the participants experience over the past week. These include five domains (physical, role, emotional, cognitive and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/HRQoL scale. The time to definitive 10-point deterioration is defined as the time from the date of randomization to the date of event, which is defined as at least 10 points absolute increase from baseline (worsening) of the corresponding scale score, with no later change below the threshold or death due to any cause

  11. Change from baseline in EORTC-QLQ-C30 [ Time Frame: Approximately up to 33 months ]
    The EORTC QLQ-C30 is a questionnaire developed to assess the health-related quality of life of cancer participants. The questionnaire contains 30 items and is composed of both multi-item scales and single-item measures based on the participants experience over the past week. These include five domains (physical, role, emotional, cognitive and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/HRQoL scale. A higher score indicates a higher presence of symptoms.

  12. Change from baseline in EORTC-QLQ-LC13 [ Time Frame: Approximately up to 33 months ]
    The EORTC QLQ LC13 is a 13-item, lung cancer specific questionnaire module, and it comprises both multi-item and single-item measures of lung cancer-associated symptoms (i.e. coughing, hemoptysis, dyspnea and pain) and side-effects from conventional chemo- and radiotherapy (i.e. hair loss, neuropathy, sore mouth and dysphagia). A higher score indicates a higher presence of symptoms.

  13. Change from baseline in EORTC-EQ-5D-5L [ Time Frame: Approximately up to 33 months ]
    The EQ-5D-5L is a generic instrument for describing and valuing health. It is based on a descriptive system that defines health in terms of 5 dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression.

  14. Change from baseline in NSCLC-SAQ [ Time Frame: Approximately up to 33 months ]
    The Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) is a 7-item, patient-reported outcome measure which assess patient-reported symptoms associated with advanced NSCLC. It contains five domains and accompanying items that were identified as symptoms of NSCLC: cough (1 item), pain (2 items), dyspnea (1 item), fatigue (2 items), and appetite (1 item).


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant has histologically confirmed locally advanced/metastatic (stage IIIB/IIIC or IV)
  • Participant has a KRAS G12C mutation present in tumor tissue or plasma prior to enrollment, as determined by a Novartis designated central laboratory or by accepted local tests.
  • Participants has received one prior platinum-based chemotherapy regimen and one prior immune checkpoint inhibitor therapy for locally advanced or metastatic disease
  • Participant has at least 1 evaluable (measurable or non-measurable) lesion by RECIST 1.1 at the screening visit.

Exclusion Criteria:

  • Participants who have previously received docetaxel (except if received in neoadjuvant or adjuvant setting with no progression within 12 months after the of end of treatment), or any other KRAS G12C inhibitor.
  • Participant has EGFR-sensitizing mutation and/or ALK rearrangement by local laboratory testing. Participants with other druggable alterations will be excluded if required by local guidelines.
  • Participant has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Participant has an history of interstitial lung disease or pneumonitis grade > 1.

Other inclusion/exclusion criteria may apply

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05132075


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
More Information
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT05132075    
Other Study ID Numbers: CJDQ443B12301
2021-002605-10 ( EudraCT Number )
First Posted: November 24, 2021    Key Record Dates
Last Update Posted: May 7, 2024
Last Verified: May 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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 https://www.clinicalstudydatarequest.com/.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
NSCLC
Non small cell lung cancer
Lung cancer
Cancer of the lung
 Cancer of lung
Pulmonary Cancer
Neoplasms, Lung
Neoplasms, Pulmonary
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
 Carcinoma, Bronchogenic
Bronchial Neoplasms
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action