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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: JDQ443; Drug: docetaxel

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
• Enrollment (Actual): 95
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • CABA, Buenos Aires, Argentina, C1414DRK
      • Novartis Investigative Site
    • Pilar, Buenos Aires, Argentina, B1629AHJ
      • Novartis Investigative Site
• Australia
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Novartis Investigative Site
    • South Brisbane, Queensland, Australia, 4101
      • Novartis Investigative Site
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Novartis Investigative Site
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Novartis Investigative Site
• China
  • Beijing, China, 100730
    • Novartis Investigative Site
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Novartis Investigative Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Novartis Investigative Site
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Novartis Investigative Site
  • Hunan
    • Changsha, Hunan, China, 410013
      • Novartis Investigative Site
  • Liaoning
    • Shengyang, Liaoning, China, 110042
      • Novartis Investigative Site
  • Shandong
    • Jinan, Shandong, China, 250117
      • Novartis Investigative Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Novartis Investigative Site
• Finland
  • Turku, Finland, 20521
    • Novartis Investigative Site
• Greece
  • Athens, Greece, 11526
    • Novartis Investigative Site
  • Heraklion Crete., Greece, 715 00
    • Novartis Investigative Site
  • GR
    • Athens, GR, Greece, 115 27
      • Novartis Investigative Site
• Hong Kong
  • Hong Kong, Hong Kong, 999077
    • Novartis Investigative Site
  • Kowloon, Hong Kong, 999077
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1121
    • Novartis Investigative Site
• Iceland
  • Reykjavik, Iceland, 101
    • Novartis Investigative Site
• India
  • Delhi, India, 110085
    • Novartis Investigative Site
  • Rajasthan
    • Jaipur, Rajasthan, India, 302019
      • Novartis Investigative Site
• Italy
  • LU
    • Lucca, LU, Italy, 55100
      • Novartis Investigative Site
  • PN
    • Aviano, PN, Italy, 33081
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00128
      • Novartis Investigative Site
• Jordan
  • Amman, Jordan, 11941
    • Novartis Investigative Site
• Lebanon
  • Ed Daoura, Lebanon, 90375
    • Novartis Investigative Site
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Novartis Investigative Site
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Novartis Investigative Site
• Mexico
  • Mexico City, Mexico, 06760
    • Novartis Investigative Site
• Portugal
  • Matosinhos Municipality, Portugal, 4454-513
    • Novartis Investigative Site
  • Porto, Portugal, 4100-180
    • Novartis Investigative Site
• Romania
  • Cluj
    • Cluj-Napoca, Cluj, Romania, 400015
      • Novartis Investigative Site
• Slovenia
  • Ljubljana, Slovenia, 1000
    • Novartis Investigative Site
• South Korea
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, South Korea, 13620
      • Novartis Investigative Site
• Spain
  • Córdoba, Spain, 14004
    • Novartis Investigative Site
  • Madrid, Spain, 28009
    • Novartis Investigative Site
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Novartis Investigative Site
  • Principality of Asturias
    • Oviedo, Principality of Asturias, Spain, 33011
      • Novartis Investigative Site
• Taiwan
  • Tainan, Taiwan, 704302
    • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10330
    • Novartis Investigative Site
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06680
    • Novartis Investigative Site
  • Adana
    • Adana, Adana, Turkey (Türkiye), 01140
      • Novartis Investigative Site
  • Bilkent-Cankaya
    • Ankara, Bilkent-Cankaya, Turkey (Türkiye), 06800
      • Novartis Investigative Site
  • Fatih
    • Istanbul, Fatih, Turkey (Türkiye), 34093
      • Novartis Investigative Site
  • Pendik
    • Istanbul, Pendik, Turkey (Türkiye), 34899
      • Novartis Investigative Site
  • Yenimahalle
    • Ankara, Yenimahalle, Turkey (Türkiye), 06500
      • Novartis Investigative Site
• United States
  • Washington
    • Renton, Washington, United States, 98055
      • Valley Medical Center Research
• Vietnam
  • Hanoi, Vietnam, 300000
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	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.	Approximately up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from date of randomization to date of death due to any cause	Approximately up to 33 months
Overall Response Rate (ORR)	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.	Approximately up to 33 months
Disease Control Rate (DCR)	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.	Approximately up to 33 months
Time To Response (TTR)	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)	Approximately up to 33 months
Duration of Response (DOR)	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.	Approximately up to 33 months
Progression-Free Survival after next line therapy (PFS2)	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.	Approximately up to 33 months
Concentration of JDQ443 and its metabolite in plasma	To characterize the pharmacokinetics of JDQ443 and its metabolite HZC320	Approximately up to 33 months
Time to definitive deterioration of Eastern Cooperative Group of Oncology Group (ECOG) performance status	Deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)	Approximately up to 33 months
Time to definitive 10-point deterioration symptom scores of chest pain, cough and dyspnea per QLQ-LC13	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	Approximately up to 33 months
Time to definitive 10-point deterioration in global health status/QoL, shortness of breath and pain per QLQ-C30	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	Approximately up to 33 months
Change from baseline in EORTC-QLQ-C30	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.	Approximately up to 33 months
Change from baseline in EORTC-QLQ-LC13	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.	Approximately up to 33 months
Change from baseline in EORTC-EQ-5D-5L	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.	Approximately up to 33 months
Change from baseline in NSCLC-SAQ	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).	Approximately up to 33 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2022
• Primary Completion (Estimated): August 25, 2026
• Study Completion (Estimated): September 23, 2026

Study Registration Dates

• First Submitted: November 11, 2021
• First Submitted That Met QC Criteria: November 11, 2021
• First Posted (Actual): November 24, 2021

Study Record Updates

• Last Update Posted (Actual): August 27, 2026
• Last Update Submitted That Met QC Criteria: August 26, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; Lung cancer; Non small cell lung cancer; Cancer of the lung; Neoplasms, Lung; Neoplasms, Pulmonary; Pulmonary Cancer; Cancer of lung
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Docetaxel; JDQ443
• Other Study ID Numbers: CJDQ443B12301; 2023 (U.S. NIH Grant/Contract: GRAMMY Museum Foundation); 2023-510082-10-00 (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 https://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