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

Non-Small Cell Lung Cancer Clinical Trial

— KontRASt-02  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05132075
• Other study ID #: CJDQ443B12301
• Secondary ID: 2021-002605-10
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 15, 2022
• Est. completion date: May 24, 2025

Study information

• Verified date: June 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 95
• Est. completion date: May 24, 2025
• Est. primary completion date: September 9, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

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

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	La Plata	Buenos Aires
Argentina	Novartis Investigative Site	Pilar	Buenos Aires
Australia	Novartis Investigative Site	Auchenflower	Queensland
Australia	Novartis Investigative Site	Hyde Park	Queensland
Australia	Novartis Investigative Site	South Brisbane	Queensland
Australia	Novartis Investigative Site	Southport	Queensland
Canada	Novartis Investigative Site	Levis	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Sherbrooke	Quebec
Chile	Novartis Investigative Site	Santiago	Region Metropolitana
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Changsha	Hunan
China	Novartis Investigative Site	Chongqing
China	Novartis Investigative Site	Fuzhou	Fujian
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Hangzhou	Zhe Jiang
China	Novartis Investigative Site	Harbin	Heilongjiang
China	Novartis Investigative Site	Hefei	Anhui
China	Novartis Investigative Site	Jinan	Shandong
China	Novartis Investigative Site	Shenyang	Shengyang
China	Novartis Investigative Site	Wuhan	Hubei
China	Novartis Investigative Site	Zhengzhou
Colombia	Novartis Investigative Site	Medellin	Antioquia
Colombia	Novartis Investigative Site	Monteria
Colombia	Novartis Investigative Site	Valledupar	Cesar
Croatia	Novartis Investigative Site	Zagreb
Finland	Novartis Investigative Site	Turku
Greece	Novartis Investigative Site	Athens	GR
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Heraklion Crete
Greece	Novartis Investigative Site	Thessaloniki
Hong Kong	Novartis Investigative Site	Hong Kong
Hong Kong	Novartis Investigative Site	Kowloon
Hong Kong	Novartis Investigative Site	Shatin New Territories
Hungary	Novartis Investigative Site	Budapest
Iceland	Novartis Investigative Site	Reykjavik
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Delhi
India	Novartis Investigative Site	Hyderabad	Andhra Pradesh
India	Novartis Investigative Site	Jaipur	Rajasthan
India	Novartis Investigative Site	Kolkata	West Bengal
India	Novartis Investigative Site	Kolkata	West Bengal
India	Novartis Investigative Site	Mumbai
India	Novartis Investigative Site	Nashik	Maharashtra
India	Novartis Investigative Site	Visakhapatnam	Andhrapradesh
Italy	Novartis Investigative Site	Aviano	PN
Italy	Novartis Investigative Site	Lucca	LU
Italy	Novartis Investigative Site	Roma	RM
Jordan	Novartis Investigative Site	Amman
Jordan	Novartis Investigative Site	Amman
Korea, Republic of	Novartis Investigative Site	Busan
Korea, Republic of	Novartis Investigative Site	Daegu	Dalseo Gu
Korea, Republic of	Novartis Investigative Site	Jinju
Korea, Republic of	Novartis Investigative Site	Seongnam Si	Gyeonggi Do
Korea, Republic of	Novartis Investigative Site	Seoul	Seocho Gu
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Lebanon	Novartis Investigative Site	Ashrafieh
Lebanon	Novartis Investigative Site	Dora
Malaysia	Novartis Investigative Site	Kuala Lumpur
Malaysia	Novartis Investigative Site	Kuching	Sarawak
Malaysia	Novartis Investigative Site	Petaling Jaya	Selangor Darul Ehsan
Malaysia	Novartis Investigative Site	Petaling Jaya	Selangor
Mexico	Novartis Investigative Site	Cuautitlan Izcalli	Estado De Mexico
Mexico	Novartis Investigative Site	Guadalajara	Jalisco
Mexico	Novartis Investigative Site	Mexico City
Mexico	Novartis Investigative Site	Veracruz
Portugal	Novartis Investigative Site	Matosinhos
Portugal	Novartis Investigative Site	Porto
Romania	Novartis Investigative Site	Cluj-Napoca
Romania	Novartis Investigative Site	Suceava
Slovenia	Novartis Investigative Site	Ljubljana
Spain	Novartis Investigative Site	Cordoba	Andalucia
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Oviedo	Asturias
Spain	Novartis Investigative Site	Pamplona	Navarra
Taiwan	Novartis Investigative Site	Tainan
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Khon Kaen	THA
Turkey	Novartis Investigative Site	Adana
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Ankara	Yenimahalle
Turkey	Novartis Investigative Site	Antalya
Turkey	Novartis Investigative Site	Cankaya Ankara
Turkey	Novartis Investigative Site	Fatih
Turkey	Novartis Investigative Site	Fatih-Istanbul
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Sakarya
United States	Valley Medical Center Research Valley Professional Center Bld	Renton	Washington
Vietnam	Novartis Investigative Site	Hanoi
Vietnam	Novartis Investigative Site	Ho Chi Minh

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Australia,  Canada,  Chile,  China,  Colombia,  Croatia,  Finland,  Greece,  Hong Kong,  Hungary,  Iceland,  India,  Italy,  Jordan,  Korea, Republic of,  Lebanon,  Malaysia,  Mexico,  Portugal,  Romania,  Slovenia,  Spain,  Taiwan,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Concentration of JDQ443 and its metabolite in plasma	To characterize the pharmacokinetics of JDQ443 and its metabolite HZC320	Approximately up to 33 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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