Clinical trial NCT05132075: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Non-Small Cell Lung Cancer
Keywords: NSCLC
Non small cell lung cancer
Lung cancer
Cancer of the lung
Cancer of lung
Pulmonary Cancer
Neoplasms, Lung
Neoplasms, Pulmonary
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-11-24
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression free survival (PFS)
timeFrame: Approximately up to 24 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Approximately up to 33 months
measure: Overall Response Rate (ORR)
timeFrame: Approximately up to 33 months
measure: Disease Control Rate (DCR)
timeFrame: Approximately up to 33 months
measure: Time To Response (TTR)
timeFrame: Approximately up to 33 months
measure: Duration of Response (DOR)
timeFrame: Approximately up to 33 months
measure: Progression-Free Survival after next line therapy (PFS2)
timeFrame: Approximately up to 33 months
measure: Concentration of JDQ443 and its metabolite in plasma
timeFrame: Approximately up to 33 months
measure: Time to definitive deterioration of Eastern Cooperative Group of Oncology Group (ECOG) performance status
timeFrame: Approximately up to 33 months
measure: Time to definitive 10-point deterioration symptom scores of chest pain, cough and dyspnea per QLQ-LC13
timeFrame: Approximately up to 33 months
measure: Time to definitive 10-point deterioration in global health status/QoL, shortness of breath and pain per QLQ-C30
timeFrame: Approximately up to 33 months
measure: Change from baseline in EORTC-QLQ-C30
timeFrame: Approximately up to 33 months
measure: Change from baseline in EORTC-QLQ-LC13
timeFrame: Approximately up to 33 months
measure: Change from baseline in EORTC-EQ-5D-5L
timeFrame: Approximately up to 33 months
measure: Change from baseline in NSCLC-SAQ
timeFrame: Approximately up to 33 months
Other outcomes:
Locations:
city: Renton
country: United States
facility: Valley Medical Center Research
state: Washington
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Pilar
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Auchenflower
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: South Brisbane
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Sherbrooke
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Fuzhou
country: China
facility: Novartis Investigative Site
state: Fujian
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Harbin
country: China
facility: Novartis Investigative Site
state: Heilongjiang
city: Changsha
country: China
facility: Novartis Investigative Site
state: Hunan
city: Shengyang
country: China
facility: Novartis Investigative Site
state: Liaoning
city: Jinan
country: China
facility: Novartis Investigative Site
state: Shandong
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Beijing
country: China
facility: Novartis Investigative Site
city: Chongqing
country: China
facility: Novartis Investigative Site
city: Turku
country: Finland
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
state: GR
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Heraklion Crete
country: Greece
facility: Novartis Investigative Site
city: Hong Kong
country: Hong Kong
facility: Novartis Investigative Site
city: Kowloon
country: Hong Kong
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Reykjavik
country: Iceland
facility: Novartis Investigative Site
city: Jaipur
country: India
facility: Novartis Investigative Site
state: Rajasthan
city: Delhi
country: India
facility: Novartis Investigative Site
city: Lucca
country: Italy
facility: Novartis Investigative Site
state: LU
city: Aviano
country: Italy
facility: Novartis Investigative Site
state: PN
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Amman
country: Jordan
facility: Novartis Investigative Site
city: Seongnam Si
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi Do
city: Dora
country: Lebanon
facility: Novartis Investigative Site
city: Kuching
country: Malaysia
facility: Novartis Investigative Site
state: Sarawak
city: Kuala Lumpur
country: Malaysia
facility: Novartis Investigative Site
city: Mexico City
country: Mexico
facility: Novartis Investigative Site
city: Matosinhos
country: Portugal
facility: Novartis Investigative Site
city: Porto
country: Portugal
facility: Novartis Investigative Site
city: Cluj-Napoca
country: Romania
facility: Novartis Investigative Site
city: Ljubljana
country: Slovenia
facility: Novartis Investigative Site
city: Cordoba
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Oviedo
country: Spain
facility: Novartis Investigative Site
state: Asturias
city: Pamplona
country: Spain
facility: Novartis Investigative Site
state: Navarra
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Tainan
country: Taiwan
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Adana
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Cankaya Ankara
country: Turkey
facility: Novartis Investigative Site
city: Fatih-Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Pendik Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Hanoi
country: Vietnam
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: