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.

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2022-001088-29-NL

Enrollment

120

Registered

2022-10-03

Start date

2022-12-19

Completion date

Unknown

Last updated

2025-02-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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 MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Interventions

Product Name: JDQ443 Product Code: JDQ443 Pharmaceutical Form: Tablet INN or Proposed INN: Not established yet. Current Sponsor code: JDQ443 Other descriptive name: JDQ443 Concentration unit: mg milli

Eligibility

Sex/Gender

All

Inclusion criteria

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 =65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

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

Design outcomes

Primary

Measure	Time frame
Main Objective: To assess the antitumor activity of JDQ443 single-agent as first-line treatment for participants with locally advanced or metastatic NSCLC whose tumors harbor a KRAS G12C mutation and a PD-L1 expression < 1%, regardless of STK11 mutation status (cohort A).;Secondary Objective: •To assess the antitumor activity of JDQ443 single-agent as first-line treatment for participants with locally advanced or metastatic NSCLC whose tumors harbor a KRAS G12C mutation, a PD-L1 expression =1% and an STK11 co-mutation (cohort B). •To assess duration of response (DOR) in both cohorts. ;Primary end point(s): Overall response rate (ORR), defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) as best overall response (BOR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by blinded independent review committee (BIRC).;Timepoint(s) of evaluation of this end point: The primary endpoint of the study is ORR, defined as the proportion of participants with a confirmed CR/PR as BOR. BOR is defined as the best response recorded from the start of the treatment until disease progression per RECIST 1.1 by BIRC. CR and PR must be confirmed by repeat assessments that should be performed not less than 4 weeks after the criteria for response were first met. Responses documented after the use of any new anti-neoplastic therapy will be considered as non-response.	—

Measure

Time frame

Main Objective: To assess the antitumor activity of JDQ443 single-agent as first-line treatment for participants with locally advanced or metastatic NSCLC whose tumors harbor a KRAS G12C mutation and a PD-L1 expression < 1%, regardless of STK11 mutation status (cohort A).;Secondary Objective: •To assess the antitumor activity of JDQ443 single-agent as first-line treatment for participants with locally advanced or metastatic NSCLC whose tumors harbor a KRAS G12C mutation, a PD-L1 expression =1% and an STK11 co-mutation (cohort B). •To assess duration of response (DOR) in both cohorts. ;Primary end point(s): Overall response rate (ORR), defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) as best overall response (BOR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by blinded independent review committee (BIRC).;Timepoint(s) of evaluation of this end point: The primary endpoint of the study is ORR, defined as the proportion of participants with a confirmed CR/PR as BOR. BOR is defined as the best response recorded from the start of the treatment until disease progression per RECIST 1.1 by BIRC. CR and PR must be confirmed by repeat assessments that should be performed not less than 4 weeks after the criteria for response were first met. Responses documented after the use of any new anti-neoplastic therapy will be considered as non-response.

—

Secondary

Measure	Time frame
Secondary end point(s): • ORR per RECIST 1.1 by BIRC. • DOR, 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. • PFS, defined as the time from the date of enrollment to the date of the first documented disease progression per RECIST 1.1 by BIRC or date of death due to any cause. • OS, defined as the time from the date of enrollment to the date of death due to any cause. • Disease control rate (DCR), defined as the proportion of participants with a BOR of confirmed CR, PR and stable disease (SD) per RECIST 1.1 by BIRC. Time to response (TTR), defined as the time from the date of enrollment to the first documented response of either CR or PR per RECIST 1.1 by BIRC. • ORR, DOR, DCR, TTR and PFS per RECIST 1.1 by local radiology assessment. • ORR, DOR, DCR and TTR per RECIST 1.1 by BIRC and by local radiology assessment. • PFS and OS • Type, frequency and severity of adverse events, changes in laboratory values, vital signs, electrocardiograms (ECGs). • Concentration of JDQ443 in plasma and derived PK parameters, as appropriate. • Time to definitive deterioration (TTD) in the NSCLC-SAQ total score, and TTD in the physical functioning (PF) scale of the EORTC QLQ-C30 • Change from baseline to each treatment visit and EOT for NSCLC-SAQ total score, pain, cough, dyspnea and items. • Change from baseline to each treatment visit and EOT for all EORTC-QLQ C30 domains, subscales and items • Change from baseline to each treatment visit and to EOT for the FACT GP5;Timepoint(s) of evaluation of this end point: For the key secondary endpoint, ORR per RECIST 1.1 by BIRC in cohort B, the same definition as in the Protocol, Section 9.3.1 applies. Treatment with JDQ443 will be considered to have clinically relevant efficacy in cohort B if an ORR of = 40% is observed with the lower bound of the 95% confidence interval = 20%.	—

Measure

Time frame

Secondary end point(s): • ORR per RECIST 1.1 by BIRC. • DOR, 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. • PFS, defined as the time from the date of enrollment to the date of the first documented disease progression per RECIST 1.1 by BIRC or date of death due to any cause. • OS, defined as the time from the date of enrollment to the date of death due to any cause. • Disease control rate (DCR), defined as the proportion of participants with a BOR of confirmed CR, PR and stable disease (SD) per RECIST 1.1 by BIRC. Time to response (TTR), defined as the time from the date of enrollment to the first documented response of either CR or PR per RECIST 1.1 by BIRC. • ORR, DOR, DCR, TTR and PFS per RECIST 1.1 by local radiology assessment. • ORR, DOR, DCR and TTR per RECIST 1.1 by BIRC and by local radiology assessment. • PFS and OS • Type, frequency and severity of adverse events, changes in laboratory values, vital signs, electrocardiograms (ECGs). • Concentration of JDQ443 in plasma and derived PK parameters, as appropriate. • Time to definitive deterioration (TTD) in the NSCLC-SAQ total score, and TTD in the physical functioning (PF) scale of the EORTC QLQ-C30 • Change from baseline to each treatment visit and EOT for NSCLC-SAQ total score, pain, cough, dyspnea and items. • Change from baseline to each treatment visit and EOT for all EORTC-QLQ C30 domains, subscales and items • Change from baseline to each treatment visit and to EOT for the FACT GP5;Timepoint(s) of evaluation of this end point: For the key secondary endpoint, ORR per RECIST 1.1 by BIRC in cohort B, the same definition as in the Protocol, Section 9.3.1 applies. Treatment with JDQ443 will be considered to have clinically relevant efficacy in cohort B if an ORR of = 40% is observed with the lower bound of the 95% confidence interval = 20%.

—

Countries

Argentina, Austria, Belgium, Brazil, Bulgaria, China, France, Germany, Greece, Hungary, India, Italy, Malaysia, Netherlands, Portugal, Singapore, Spain, Thailand, Türkiye, United Kingdom, United States

Contacts

Public ContactClinical Trial Information Desk

Novartis Pharma AG

clinicaltrial.enquiries@novartis.com+4461 324 1111

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026