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.
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| ClinicalTrials.gov Identifier: NCT05445843 |
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Recruitment Status :
Recruiting
First Posted : July 6, 2022
Last Update Posted : February 28, 2024
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Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
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Brief Summary:
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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| 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 | Drug: JDQ443 | Phase 2 |
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 (Clinical Trial) |
| Estimated Enrollment : | 120 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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. |
| Actual Study Start Date : | December 6, 2022 |
| Estimated Primary Completion Date : | November 2, 2026 |
| Estimated Study Completion Date : | November 30, 2027 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Lung cancer
MedlinePlus related topics:
Lung Cancer
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: JDQ443
JDQ443 orally administered |
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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.
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Drug: JDQ443
JDQ443 orally administered |
Primary Outcome Measures :
- Overall response rate (ORR) by blinded independent review committee (BIRC) in cohort A [ Time Frame: Up to approximately 24 months ]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
Secondary Outcome Measures :
- ORR by BIRC in cohort B [ Time Frame: Up to approximately 24 months ]ORR is defined as the percentage of participants with a CR or PR as BOR per RECIST 1.1 by BIRC in cohort B
- Duration of response (DOR) by BIRC in both cohorts [ Time Frame: From first documented response to disease progression or death, up to approximately 24 months ]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.
- Progression Free Survival (PFS) by BIRC in both cohorts [ Time Frame: From first study treatment to first documented progression or death, up to approximately 24 months ]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.
- Overall survival (OS) in both cohorts [ Time Frame: From enrollment to death, up to approximately 36 months ]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.
- Disease control rate (DCR) by BIRC in both cohorts [ Time Frame: Up to approximately 24 months ]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.
- Time to response (TTR) by BIRC in both cohorts [ Time Frame: From enrollment to first documented response, up to approximately 24 months ]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.
- ORR by local radiology assessment in both cohorts [ Time Frame: Up to approximately 24 months ]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.
- DOR by local review assessment in both cohorts [ Time Frame: From first documented response to disease progression or death, up to approximately 24 months ]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.
- DCR by local review assessment in both cohorts [ Time Frame: Up to approximately 24 months ]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.
- TTR by local review assessment in both cohorts [ Time Frame: From enrollment to first documented response, up to approximately 24 months ]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.
- PFS by local review assessment in both cohorts [ Time Frame: From first study treatment to first documented progression or death, up to approximately 24 months ]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.
- 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) [ Time Frame: Up to approximately 24 months ]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
- 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) [ Time Frame: From first documented response to disease progression or death, up to approximately 24 months ]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.
- 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) [ Time Frame: Up to approximately 24 months ]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
- 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) [ Time Frame: From enrollment to first documented response, up to approximately 24 months ]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
- 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) [ Time Frame: From first study treatment to first documented progression or death, up to 24 months ]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
- OS for participants whose tumors harbor an STK11 mutation regardless of PD-L1 expression status (pooled from both cohorts) [ Time Frame: From enrollment to death, up to approximately 36 months ]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
- Maximum concentration (Cmax) of JDQ443 in plasma [ Time Frame: Up to approximately 24 months ]Blood samples will be collected for pharmacokinetics characterization.
- Time to reach maximum concentration at steady-state (Tmax,ss) of JDQ443 in plasma [ Time Frame: Up to approximately 24 months ]Blood samples will be collected for pharmacokinetics characterization.
- Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of JDQ443 in plasma [ Time Frame: Up to approximately 24 months ]Blood samples will be collected for pharmacokinetics characterization.
- Area Under the Curve From Time Zero to the last measurable concentration sampling time at steady-state (AUClastss) of JDQ443 in plasma [ Time Frame: Up to approximately 24 months ]Blood samples will be collected for pharmacokinetics characterization.
- Observed concentration at the end of a dosing interval at steady-state (Cmin,ss) of JDQ443 in plasma [ Time Frame: Up to approximately 24 months ]Blood samples will be collected for pharmacokinetics characterization.
- Total body clearance (CL/F) of JDQ443 from the plasma [ Time Frame: Up to approximately 24 months ]Blood samples will be collected for pharmacokinetics characterization.
- Time to definitive deterioration (TTDD) in NSCLC-SAQ total score [ Time Frame: From baseline up to approximately 24 months ]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.
- TTDD in the physical functioning scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30 [ Time Frame: From baseline up to approximately 24 months ]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).
- Chain from baseline in NSCLC-SAQ [ Time Frame: From baseline up to approximately 24 months ]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.
- Change from baseline in EORTC QLQ-C30 [ Time Frame: From baseline up to approximately 24 months ]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).
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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).
- 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05445843
Contacts
| Contact: Novartis Pharmaceuticals | 1-888-669-6682 | novartis.email@novartis.com | |
| Contact: Novartis Pharmaceuticals | +41613241111 |
Locations
Show 79 study locations
Sponsors and Collaborators
Novartis Pharmaceuticals
| Responsible Party: | Novartis Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT05445843 |
| Other Study ID Numbers: |
CJDQ443B12201 2022-001088-29 ( EudraCT Number ) |
| First Posted: | July 6, 2022 Key Record Dates |
| Last Update Posted: | February 28, 2024 |
| Last Verified: | February 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
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Lung cancer NSCLC KRAS G12C |
STK11 PD-L1 JDQ443 |
Additional relevant MeSH terms:
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Lung Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site |
Neoplasms Lung Diseases Respiratory Tract Diseases |