Clinical trial NCT05445843: Study of Efficacy and Safety of JDQ443 Single-agent as First-line Treatment for Patients With Locally Advanced or Metastatic KRAS G12C- Mutated Non-small Cell Lung Cancer With a PD-L1 Expression < 1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation.
Official title: KontRASt-06: An Open-label Phase II Trial Evaluating the Activity and Safety of JDQ443 Single-agent as First-line Treatment for Patients With Locally Advanced or Metastatic KRAS G12C-mutated Non-small Cell Lung Cancer With a PD-L1 Expression < 1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Locally Advanced or Metastatic KRAS G12C-mutated NSCLC With a PD-L1 Expression <1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation
Keywords: Lung cancer
NSCLC
KRAS G12C
STK11
PD-L1
JDQ443
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2022-07-06
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to evaluate the antitumor activity and safety of JDQ443 single-agent as first-line treatment for participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors harbor a KRAS G12C mutation and have a PD-L1 expression \< 1% (cohort A) or a PD-L1 expression ≥ 1% and an STK11 co-mutation (cohort B).

Detailed description: This is a non-randomized, open-label, single-arm, multicenter, phase II study evaluating the antitumor activity and safety of JDQ443 single-agent as first-line treatment for participants with locally advanced or metastatic KRAS G12C-mutated NSCLC.

The study will have 2 non-comparative cohorts that will recruit participants in parallel according to the following characteristics:

* Cohort A: participants whose tumors harbor a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status (N=90).
* Cohort B: participants whose tumors harbor a KRAS G12C mutation, a PD-L1 expression ≥ 1% and an STK11 co-mutation (N=30).

The study treatment begins on Cycle 1 Day 1 (C1D1) with the first administration of JDQ443. One treatment cycle consists of 21 (±3) days.

Study completion is defined as the earliest occurrence of one of the following:

* The last participant completes last study visit (and the assessments associated with this visit have been documented and followed-up appropriately by the Investigator), dies, withdraws consent, or is lost to follow-up, whichever comes first.\]
* In the event of an early study termination decision, the date of that decision.
* Another clinical study becomes available that can continue to provide JDQ443 to study participants and all participants with ongoing treatment are transferred to that clinical study.

Eligibility criteria: Key Inclusion criteria

* Histologically confirmed locally advanced (stage IIIb/IIIc not eligible for definitive chemoradiation or surgical resection with curative intent) or metastatic (stage IV) NSCLC without previous systemic treatment for metastatic disease. Prior (neo)adjuvant treatment with chemotherapy and/or immunotherapy, or prior radiotherapy administered sequentially or concomitantly with chemotherapy and/or immunotherapy for localized or locally advanced disease are accepted if the time between therapy completion and enrollment is \> 12 months.
* Presence of a KRAS G12C mutation (all participants) and:

  * Cohort A: PD-L1 expression \< 1%, regardless of STK11 mutation status
  * Cohort B: PD-L1 expression ≥ 1% and an STK11 co-mutation
* At least one measurable lesion per RECIST 1.1.
* ECOG performance status ≤ 1.
* Participants capable of swallowing study medication.

Key Exclusion criteria

* Participants whose tumors harbor an EGFR-sensitizing mutation and/or ALK rearrangement by local laboratory testing. Participants with other known druggable alterations will be excluded, if required by local guidelines
* Previous use of a KRAS G12C inhibitor or previous systemic treatment for metastatic NSCLC.
* A medical condition that results in increased photosensitivity (i.e., solar urticaria, lupus erythematosus, etc.).
* Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Participants who are taking a prohibited medication (strong CYP3A inducers) that cannot be discontinued at least seven days prior to the first dose of study treatment and for the duration of the study.

Other inclusion/exclusion criteria may apply

Primary outcomes:
measure: Overall Response Rate (ORR) as determined by the Investigator in Cohort A
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Key Secondary Outcome Measure: Overall Response Rate (ORR) as determined by the Investigator in Cohort B
timeFrame: Up to approximately 24 months
measure: Number of adverse events and serious adverse events as assessed by CTCAE criteria
timeFrame: Up to approximately 60 months
measure: Maximum concentration (Cmax) of JDQ443 in plasma
timeFrame: Up to approximately 24 months
measure: Time to reach maximum concentration at steady-state (Tmax,ss) of JDQ443 in plasma
timeFrame: Up to approximately 24 months
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of JDQ443 in plasma
timeFrame: Up to approximately 24 months
measure: Area Under the Curve From Time Zero to the last measurable concentration sampling time at steady-state (AUClastss) of JDQ443 in plasma
timeFrame: Up to approximately 24 months
measure: Observed concentration at the end of a dosing interval at steady-state (Cmin,ss) of JDQ443 in plasma
timeFrame: Up to approximately 24 months
measure: Total body clearance (CL/F) of JDQ443 from the plasma
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Providence
country: United States
facility: The Brown University Oncology Group
state: Rhode Island
city: Pilar
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Cordoba
country: Argentina
facility: Novartis Investigative Site
city: Cordoba
country: Argentina
facility: Novartis Investigative Site
city: Feldkirch
country: Austria
facility: Novartis Investigative Site
city: Wels
country: Austria
facility: Novartis Investigative Site
city: Sint Niklaas
country: Belgium
facility: Novartis Investigative Site
state: Oost Vlaanderen
city: Roeselare
country: Belgium
facility: Novartis Investigative Site
city: Salvador
country: Brazil
facility: Novartis Investigative Site
state: BA
city: Belo Horizonte
country: Brazil
facility: Novartis Investigative Site
city: Wuhan
country: China
facility: Novartis Investigative Site
state: Hubei
city: Changsha
country: China
facility: Novartis Investigative Site
state: Hunan
city: Beijing
country: China
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
state: Bouches Du Rhone
city: Bron
country: France
facility: Novartis Investigative Site
city: Montpellier
country: France
facility: Novartis Investigative Site
city: Saint Herblain
country: France
facility: Novartis Investigative Site
city: Strasbourg Cedex
country: France
facility: Novartis Investigative Site
city: Halle Saale
country: Germany
facility: Novartis Investigative Site
state: Sachsen-Anhalt
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Kempten
country: Germany
facility: Novartis Investigative Site
city: Oldenburg
country: Germany
facility: Novartis Investigative Site
city: Tuebingen
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Matrahaza
country: Hungary
facility: Novartis Investigative Site
city: Thellakom Kottayam
country: India
facility: Novartis Investigative Site
state: Kerala
city: Varanasi
country: India
facility: Novartis Investigative Site
state: Uttarpradesh
city: Bari
country: Italy
facility: Novartis Investigative Site
state: BA
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Orbassano
country: Italy
facility: Novartis Investigative Site
state: TO
city: Kuching
country: Malaysia
facility: Novartis Investigative Site
state: Sarawak
city: Pulau Pinang
country: Malaysia
facility: Novartis Investigative Site
city: Breda
country: Netherlands
facility: Novartis Investigative Site
city: Leeuwarden
country: Netherlands
facility: Novartis Investigative Site
city: Porto
country: Portugal
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Diyarbakir
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Torquay
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: