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.

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.

This study aims to assess 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 a PD-L1 expression < 1% regardless of STK11 mutation status (cohort A), or a PD-L1 expression ≥ 1% and an STK11 co-mutation (cohort B).

Study Overview

• Status: Recruiting
• 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
• Intervention / Treatment: Drug: JDQ443

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 (Cohort A and B) that will recruit participants in parallel.

The study treatment begins on Cycle 1 Day 1 (C1D1) with the first administration of JDQ443. Each cycle is 21 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.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1426AGE
    • Recruiting
    • Novartis Investigative Site
  • Cordoba, Argentina, X5016KEH
    • Recruiting
    • Novartis Investigative Site
  • Cordoba, Argentina, X5000JHQ
    • Recruiting
    • Novartis Investigative Site
  • Buenos Aires
    • Pilar, Buenos Aires, Argentina, B1629AHJ
      • Recruiting
      • Novartis Investigative Site
  • Caba
    • Buenos Aires, Caba, Argentina, C1431FWO
      • Recruiting
      • Novartis Investigative Site
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000DSV
      • Recruiting
      • Novartis Investigative Site
• Austria
  • Feldkirch, Austria, A 6807
    • Recruiting
    • Novartis Investigative Site
  • Klagenfurt, Austria, 9020
    • Recruiting
    • Novartis Investigative Site
  • Wels, Austria, A-4600
    • Recruiting
    • Novartis Investigative Site
• Belgium
  • Roeselare, Belgium, 8800
    • Recruiting
    • Novartis Investigative Site
  • Oost Vlaanderen
    • Sint Niklaas, Oost Vlaanderen, Belgium, 9100
      • Recruiting
      • Novartis Investigative Site
• Brazil
  • Belo Horizonte, Brazil, 30360 680
    • Recruiting
    • Novartis Investigative Site
  • Rio Grande Do Sul, Brazil, 90035-001
    • Recruiting
    • Novartis Investigative Site
  • Rio de Janeiro, Brazil, 22271-110
    • Recruiting
    • Novartis Investigative Site
  • BA
    • Salvador, BA, Brazil, 41825-010
      • Recruiting
      • Novartis Investigative Site
• Bulgaria
  • Branipole, Bulgaria, 4109
    • Recruiting
    • Novartis Investigative Site
  • Plovdiv, Bulgaria, 4004
    • Recruiting
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1303
    • Recruiting
    • Novartis Investigative Site
• China
  • Beijing, China, 100036
    • Recruiting
    • Novartis Investigative Site
  • Beijing, China, 100021
    • Recruiting
    • Novartis Investigative Site
  • Shanyang, China, 110005
    • Recruiting
    • Novartis Investigative Site
  • Zhengzhou, China, 450008
    • Recruiting
    • Novartis Investigative Site
  • Guang Dong Province
    • Guang Zhou, Guang Dong Province, China, 510120
      • Withdrawn
      • Novartis Investigative Site
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Novartis Investigative Site
    • Wuhan, Hubei, China, 430030
      • Recruiting
      • Novartis Investigative Site
  • Hunan
    • Changsha, Hunan, China, 410013
      • Recruiting
      • Novartis Investigative Site
  • Shanxi
    • Xian, Shanxi, China, 710061
      • Recruiting
      • Novartis Investigative Site
• France
  • Bron, France, 69677
    • Recruiting
    • Novartis Investigative Site
  • Montpellier, France, 34070
    • Recruiting
    • Novartis Investigative Site
  • Paris, France, 75014
    • Recruiting
    • Novartis Investigative Site
  • Paris, France, 75970
    • Recruiting
    • Novartis Investigative Site
  • Saint Herblain, France, 44805
    • Recruiting
    • Novartis Investigative Site
  • Strasbourg Cedex, France, 67091
    • Recruiting
    • Novartis Investigative Site
  • Bouches Du Rhone
    • Marseille cedex 20, Bouches Du Rhone, France, 13915
      • Recruiting
      • Novartis Investigative Site
• Germany
  • Berlin, Germany, 13125
    • Recruiting
    • Novartis Investigative Site
  • Halle (Saale), Germany, 06120
    • Recruiting
    • Novartis Investigative Site
  • Harburg, Germany, 31787
    • Recruiting
    • Novartis Investigative Site
  • Hemer, Germany, 58675
    • Recruiting
    • Novartis Investigative Site
  • Kempten, Germany, 87439
    • Recruiting
    • Novartis Investigative Site
  • Oldenburg, Germany, 26121
    • Recruiting
    • Novartis Investigative Site
  • Tuebingen, Germany, 72076
    • Recruiting
    • Novartis Investigative Site
• Greece
  • Athens, Greece, 11526
    • Recruiting
    • Novartis Investigative Site
  • GR
    • Athens, GR, Greece, 115 27
      • Recruiting
      • Novartis Investigative Site
• Hungary
  • Matrahaza, Hungary, 3200
    • Recruiting
    • Novartis Investigative Site
  • Pest
    • Torokbalint, Pest, Hungary, 2045
      • Recruiting
      • Novartis Investigative Site
• India
  • Puducherry, India, 605006
    • Recruiting
    • Novartis Investigative Site
  • Uttarpradesh
    • Varanasi, Uttarpradesh, India, 221005
      • Recruiting
      • Novartis Investigative Site
  • West Bengal
    • Kolkata, West Bengal, India, 700160
      • Recruiting
      • Novartis Investigative Site
• Italy
  • BA
    • Bari, BA, Italy, 70124
      • Recruiting
      • Novartis Investigative Site
  • MI
    • Rozzano, MI, Italy, 20089
      • Recruiting
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00128
      • Recruiting
      • Novartis Investigative Site
  • TO
    • Orbassano, TO, Italy, 10043
      • Recruiting
      • Novartis Investigative Site
  • VA
    • Varese, VA, Italy, 21100
      • Recruiting
      • Novartis Investigative Site
• Malaysia
  • Pulau Pinang, Malaysia, 10990
    • Recruiting
    • Novartis Investigative Site
  • Kedah
    • Alor Setar, Kedah, Malaysia, 05460
      • Recruiting
      • Novartis Investigative Site
  • Pahang
    • Kuantan, Pahang, Malaysia, 25200
      • Recruiting
      • Novartis Investigative Site
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Recruiting
      • Novartis Investigative Site
• Netherlands
  • Breda, Netherlands, 4818 CK
    • Recruiting
    • Novartis Investigative Site
  • Leeuwarden, Netherlands, 8934 AD
    • Recruiting
    • Novartis Investigative Site
• Portugal
  • Lisboa, Portugal, 1998-018
    • Recruiting
    • Novartis Investigative Site
  • Porto, Portugal, 4100-180
    • Recruiting
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 168583
    • Recruiting
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28041
    • Recruiting
    • Novartis Investigative Site
  • Andalucia
    • Sevilla, Andalucia, Spain, 41013
      • Recruiting
      • Novartis Investigative Site
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Recruiting
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Recruiting
      • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10400
    • Recruiting
    • Novartis Investigative Site
  • Bangkok, Thailand, 10700
    • Recruiting
    • Novartis Investigative Site
  • Hat Yai
    • Songkhla, Hat Yai, Thailand, 90110
      • Recruiting
      • Novartis Investigative Site
• Turkey
  • Adana, Turkey, 01140
    • Recruiting
    • Novartis Investigative Site
  • Ankara, Turkey, 06560
    • Recruiting
    • Novartis Investigative Site
  • Diyarbakir, Turkey, 21000
    • Recruiting
    • Novartis Investigative Site
  • Edirne, Turkey, 22030
    • Recruiting
    • Novartis Investigative Site
  • Istanbul, Turkey, 34214
    • Recruiting
    • Novartis Investigative Site
  • Izmir, Turkey, 35575
    • Recruiting
    • Novartis Investigative Site
• United Kingdom
  • Devon
    • Torquay, Devon, United Kingdom, TQ2 7AA
      • Recruiting
      • Novartis Investigative Site
• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Recruiting
      • Hartford Hospital
      • Contact: Joshua Lopez; Phone Number: 860-545-5000; Email: Joshua.lopez@hhchealth.org
      • Principal Investigator: Wylie Hosmer
  • Ohio
    • Toledo, Ohio, United States, 43606
      • Recruiting
      • University of Toledo Precision Oncology
      • Contact: Katherine Behrens; Email: Katherine.Behrens@utoledo.edu
      • Principal Investigator: Danae Hamouda
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Recruiting
      • The Brown University Oncology Group
      • Contact: Robert Jarbadan; Phone Number: 401-444-5435; Email: rjarbadan@lifespan.org
      • Principal Investigator: Christopher Azzoli

Participation Criteria

Eligibility Criteria

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

Description

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).
• Know active (unstable/symptomatic) 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A- PD-L1<1%; Participants whose tumors harbor a KRAS G12C mutation and a PD-L1 expression <1%, regardless of STK11 mutation status.	Drug: JDQ443; JDQ443 orally administered
Experimental: Cohort B- PD-L1≥ 1% and STK11 mutation; Participants whose tumors harbor a KRAS G12C mutation, a PD-L1 expression ≥ 1% and an STK11 co-mutation.	Drug: JDQ443; JDQ443 orally administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR) by blinded independent review committee (BIRC) in cohort A	ORR is defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) as best overall response (BOR) per response evaluation criteria in solid tumors (RECIST) version 1.1 by BIRC in cohort A	Up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR by BIRC in cohort B	ORR is defined as the percentage of participants with a CR or PR as BOR per RECIST 1.1 by BIRC in cohort B	Up to approximately 24 months
Duration of response (DOR) by BIRC in both cohorts	DOR is defined as the time from the first occurrence of a PR or a CR per RECIST 1.1 by BIRC to the occurrence of disease progression or death due to any cause. DOR will be calculated separately for each of the two cohorts.	From first documented response to disease progression or death, up to approximately 24 months
Progression Free Survival (PFS) by BIRC in both cohorts	PFS is defined as the time from the date of first dose of study treatment to the date of the first documented disease progression per RECIST 1.1 by BIRC or date of death due to any cause. PFS will be calculated separately for each of the two cohorts.	From first study treatment to first documented progression or death, up to approximately 24 months
Overall survival (OS) in both cohorts	OS is defined as the time from the date of enrollment to the date of death due to any cause. OS will be calculated separately for each of the two cohorts.	From enrollment to death, up to approximately 36 months
Disease control rate (DCR) by BIRC in both cohorts	DCR is defined as the percentage of participants with a BOR of confirmed CR, PR and stable disease (SD) per RECIST 1.1 by BIRC. DCR will be calculated separately for each of the two cohorts.	Up to approximately 24 months
Time to response (TTR) by BIRC in both cohorts	TTR is defined as the time from the date of enrollment to the date of first documented response of either CR or PR per RECIST 1.1 by BIRC. TTR will be calculated separately for each of the two cohorts.	From enrollment to first documented response, up to approximately 24 months
ORR by local radiology assessment in both cohorts	ORR is defined as the percentage of participants with a CR or PR as BOR per RECIST 1.1 by local review assessment. ORR will be calculated separately for each of the two cohorts.	Up to approximately 24 months
DOR by local review assessment in both cohorts	DOR is defined as the time from the first occurrence of a PR or a CR per RECIST 1.1 by local review assessment to the occurrence of disease progression or death due to any cause. DOR will be calculated separately for each of the two cohorts.	From first documented response to disease progression or death, up to approximately 24 months
DCR by local review assessment in both cohorts	DCR is defined as the percentage of participants with a BOR of confirmed CR, PR and SD per RECIST 1.1 by local review assessment. DCR will be calculated separately for each of the two cohorts.	Up to approximately 24 months
TTR by local review assessment in both cohorts	TTR is defined as the time from the date of enrollment to the date of first documented response of either CR or PR per RECIST 1.1 by local review assessment. TTR will be calculated separately for each of the two cohorts.	From enrollment to first documented response, up to approximately 24 months
PFS by local review assessment in both cohorts	PFS is defined as the time from the date of first dose of study treatment to the date of the first documented disease progression per RECIST 1.1 by local review assessment or date of death due to any cause. PFS will be calculated separately for each of the two cohorts.	From first study treatment to first documented progression or death, up to approximately 24 months
ORR by BIRC and local radiology assessment for participants whose tumors harbor an STK11 mutation regardless of PD-L1 expression status (pooled from both cohorts)	ORR is defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) as best overall response (BOR) per RECIST 1.1 by local review assessment and by BIRC. ORR will be calculated for all participants whose tumors harbor an STK11 mutation by pooling participants from both cohorts	Up to approximately 24 months
DOR by BIRC and local radiology assessment for participants whose tumors harbor an STK11 mutation regardless of PD-L1 expression status (pooled from both cohorts)	DOR is defined as the time from the first occurrence of a PR or a CR per RECIST 1.1 by local review assessment and by BIRC to the occurrence of disease progression or death due to any cause. DOR will be calculated for all participants whose tumors harbor an STK11 mutation by pooling participants from both cohorts.	From first documented response to disease progression or death, up to approximately 24 months
DCR by BIRC and local radiology assessment for participants whose tumors harbor an STK11 mutation regardless of PD-L1 expression status (pooled from both cohorts)	DCR is defined as the percentage of participants with a BOR of confirmed CR, PR and stable disease (SD) per RECIST 1.1 by local review assessment and by BIRC. DCR will be calculated for all participants whose tumors harbor an STK11 mutation by pooling participants from both cohorts	Up to approximately 24 months
TTR by BIRC and local radiology assessment for participants whose tumors harbor an STK11 mutation regardless of PD-L1 expression status (pooled from both cohorts)	TTR is defined as the time from the date of enrollment to the date of first documented response of either CR or PR per RECIST 1.1 by local review assessment and by BIRC. TTR will be calculated for all participants whose tumors harbor an STK11 mutation by pooling participants from both cohorts	From enrollment to first documented response, up to approximately 24 months
PFS by BIRC and local radiology assessment for participants whose tumors harbor an STK11 mutation regardless of PD-L1 expression status (pooled from both cohorts)	PFS is defined as the time from the date of first dose of study treatment to the date of the first documented disease progression per RECIST 1.1 by local review assessment and BIRC or date of death due to any cause. PFS will be calculated for all participants whose tumors harbor an STK11 mutation by pooling participants from both cohorts	From first study treatment to first documented progression or death, up to 24 months
OS for participants whose tumors harbor an STK11 mutation regardless of PD-L1 expression status (pooled from both cohorts)	OS is defined as the time from the date of enrollment to the date of death due to any cause. OS will be calculated for all participants whose tumors harbor an STK11 mutation by pooling participants from both cohorts	From enrollment to death, up to approximately 36 months
Maximum concentration (Cmax) of JDQ443 in plasma	Blood samples will be collected for pharmacokinetics characterization.	Up to approximately 24 months
Time to reach maximum concentration at steady-state (Tmax,ss) of JDQ443 in plasma	Blood samples will be collected for pharmacokinetics characterization.	Up to approximately 24 months
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of JDQ443 in plasma	Blood samples will be collected for pharmacokinetics characterization.	Up to approximately 24 months
Area Under the Curve From Time Zero to the last measurable concentration sampling time at steady-state (AUClastss) of JDQ443 in plasma	Blood samples will be collected for pharmacokinetics characterization.	Up to approximately 24 months
Observed concentration at the end of a dosing interval at steady-state (Cmin,ss) of JDQ443 in plasma	Blood samples will be collected for pharmacokinetics characterization.	Up to approximately 24 months
Total body clearance (CL/F) of JDQ443 from the plasma	Blood samples will be collected for pharmacokinetics characterization.	Up to approximately 24 months
Chain from baseline in NSCLC-SAQ	The NSCLC-SAQ is a 7-item, patient-reported outcome measure which assess patient-reported symptoms associated with advanced NSCLC: cough, pain, dyspnea, fatigue, and appetite.	From baseline up to approximately 24 months
Change from baseline in EORTC QLQ-C30	The EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional and social functioning), 3 symptom scales (fatigue, pain and nausea/vomiting), a GHS/QoL scale, and six single items (constipation, diarrhea, insomnia, shortness of breath, appetite loss and financial difficulties).	From baseline up to approximately 24 months
Time to definitive deterioration (TTDD) in NSCLC-SAQ total score	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: cough, pain, dyspnea, fatigue, and appetite.	From baseline up to approximately 24 months
TTDD in the physical functioning scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30	The EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional and social functioning), 3 symptom scales (fatigue, pain and nausea/vomiting), a GHS/QoL scale, and six single items (constipation, diarrhea, insomnia, shortness of breath, appetite loss and financial difficulties).	From baseline up to approximately 24 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2022
• Primary Completion (Estimated): November 2, 2026
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: June 30, 2022
• First Submitted That Met QC Criteria: June 30, 2022
• First Posted (Actual): July 6, 2022

Study Record Updates

• Last Update Posted (Estimated): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: NSCLC; Lung cancer; PD-L1; KRAS G12C; STK11; JDQ443
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: CJDQ443B12201; 2022-001088-29 (EudraCT 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 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