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

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

Tracking Information

• First Submitted Date: November 11, 2021
• First Posted Date: November 24, 2021
• Last Update Posted Date: May 7, 2024
• Actual Study Start Date: June 15, 2022
• Estimated Primary Completion Date: April 21, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 11, 2021)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 10, 2022)

• 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
• 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.
• 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.
• 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)
• 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.
• 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.
• 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
• 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)
• 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
• 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
• 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.
• 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.
• 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.
• 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).

Original Secondary Outcome Measures (submitted: November 11, 2021)

• 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
• 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.
• 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.
• 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)
• 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.
• 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.
• 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
• 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)
• 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
• Time to definitive 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
• 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.
• 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.
• 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.
• 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).
• PFS based on KRAS G12C mutation status in plasma. [ Time Frame: Approximately up to 33 months ]
  To compare the clinical outcomes for JDQ443 vs docetaxel based on KRAS G12C mutation status in plasma
• OS based on KRAS G12C mutation status in plasma. [ Time Frame: Approximately up to 33 months ]
  To compare the clinical outcomes for JDQ443 vs docetaxel based on KRAS G12C mutation status in plasma
• ORR based on KRAS G12C mutation status in plasma. [ Time Frame: Approximately up to 33 months ]
  To compare the clinical outcomes for JDQ443 vs docetaxel based on KRAS G12C mutation status in plasma

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of JDQ443 in Comparison With Docetaxel in Participants With Locally Advanced or Metastatic KRAS G12C Mutant Non-small Cell Lung Cancer
• 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
• 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.

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 Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer

Intervention

• Drug: JDQ443
  JDQ443 tablets, orally administered
• Drug: docetaxel
  docetaxel concentrated solution for infusion, intravenously administered

Study Arms

• Experimental: JDQ443
  Participants will be treated with JDQ443
  Intervention: Drug: JDQ443
• Active Comparator: Docetaxel
  Participant will be treated with docetaxel following local guidelines as per standard of care and product labels
  Intervention: Drug: docetaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 11, 2021): 360
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2025
• Estimated Primary Completion Date: April 21, 2025 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Novartis Pharmaceuticals; 1-888-669-6682; novartis.email@novartis.com

Contact: Novartis Pharmaceuticals; +41613241111

• Listed Location Countries: Argentina, Australia, Brazil, Bulgaria, Canada, Chile, China, Colombia, Croatia, Czechia, Denmark, Estonia, Finland, Greece, Hong Kong, Hungary, Iceland, India, Italy, Jordan, Korea, Republic of, Lebanon, Malaysia, Mexico, Norway, Poland, Portugal, Romania, Serbia, Slovenia, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States, Vietnam

Administrative Information

• NCT Number: NCT05132075
• Other Study ID Numbers: CJDQ443B12301; 2021-002605-10 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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/.

• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: May 2024