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.

NCT05445843 | Active Not Recruiting Phase 2 Results FDA Drug

• 2 other identifiers: CJDQ443B122012024-511708-18-00
• Study Type: interventional
• Target: 95
• Locations: 19 countries
• Sites: 53

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).

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

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) as Determined by the Investigator in Cohort A

  Overall Response Rate (ORR) was 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 version 1.1 (RECIST 1.1) as determined by the Investigator in Cohort A.

  Up to approximately 22 months

Secondary Outcomes (12)

• Key Secondary Outcome Measure: Overall Response Rate (ORR) as Determined by the Investigator in Cohort B

  Up to approximately 22 months

• Number of Adverse Events and Serious Adverse Events as Assessed by CTCAE Criteria

  Up to approximately 59 months

• Plasma JDQ443 Concentration in All Participants

  Cycle 1 Day 1 (predose/0hour, 4 hours and 6 hours), Cycle 1 Day 15 (predose/0hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours and 12 hours). Cycles 3, 5 and 7 Day 1 (predose/0hour). 1 cycle = 21 days.

• Plasma JDQ443 Concentration in Chinese Participants

  Cycle 1 Day 1 (predose/0hour, 4 hours and 6 hours), Cycle 1 Day 15 (predose/0hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours and 12 hours). Cycles 3, 5 and 7 Day 1 (predose/0hour). 1 cycle = 21 days.

• Plasma JDQ443 Concentration in Non-Chinese Participants

  Cycle 1 Day 1 (predose/0hour, 4 hours and 6 hours), Cycle 1 Day 15 (predose/0hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours and 12 hours). Cycles 3, 5 and 7 Day 1 (predose/0hour). 1 cycle = 21 days.

Study Arms (2)

Cohort A- PD-L1<1%

EXPERIMENTAL

Participants whose tumors harbor a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status.

Drug: JDQ443

Cohort B- PD-L1≥ 1% and STK11 mutation

EXPERIMENTAL

Participants whose tumors harbor a KRAS G12C mutation, a PD-L1 expression ≥ 1% and an STK11 co-mutation.

Drug: JDQ443

Interventions

JDQ443 DRUG

JDQ443 per os (PO) 200 mg twice a day continuously

Cohort A- PD-L1<1%; Cohort B- PD-L1≥ 1% and STK11 mutation

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (53)

The Brown University Oncology Group

Providence, Rhode Island, 02903, United States

Location

Novartis Investigative Site

Pilar, Buenos Aires, B1629AHJ, Argentina

Location

Novartis Investigative Site

Buenos Aires, C1426AGE, Argentina

Location

Novartis Investigative Site

Córdoba, X5000JHQ, Argentina

Location

Novartis Investigative Site

Córdoba, X5016KEH, Argentina

Location

Novartis Investigative Site

Feldkirch, A 6807, Austria

Location

Novartis Investigative Site

Wels, A-4600, Austria

Location

Novartis Investigative Site

Sint-Niklaas, Oost Vlaanderen, 9100, Belgium

Location

Novartis Investigative Site

Roeselare, West-Vlaanderen, 8800, Belgium

Location

Novartis Investigative Site

Roeselare, 8800, Belgium

Location

Novartis Investigative Site

Salvador, Estado de Bahia, 41825-010, Brazil

Location

Novartis Investigative Site

Belo Horizonte, 30360 680, Brazil

Location

Novartis Investigative Site

Rio de Janeiro, 22271-110, Brazil

Location

Novartis Investigative Site

Wuhan, Hubei, 430030, China

Location

Novartis Investigative Site

Changsha, Hunan, 410013, China

Location

Novartis Investigative Site

Beijing, 100036, China

Location

Novartis Investigative Site

Marseille, Bouches Du Rhone, 13915, France

Location

Novartis Investigative Site

Bron, 69677, France

Location

Novartis Investigative Site

Montpellier, 34070, France

Location

Novartis Investigative Site

Saint-Herblain, 44805, France

Location

Novartis Investigative Site

Strasbourg, 67091, France

Location

Novartis Investigative Site

Kempten (Allgäu), Bavaria, 87439, Germany

Location

Novartis Investigative Site

Halle, Saxony-Anhalt, 06120, Germany

Location

Novartis Investigative Site

Hamburg, 21075, Germany

Location

Novartis Investigative Site

Kempten, 87439, Germany

Location

Novartis Investigative Site

Oldenburg, 26121, Germany

Location

Novartis Investigative Site

Tübingen, 72076, Germany

Location

Novartis Investigative Site

Athens, 11526, Greece

Location

Novartis Investigative Site

Mátraháza, 3200, Hungary

Location

Novartis Investigative Site

Thellakom Kottayam, Kerala, 686016, India

Location

Novartis Investigative Site

Varanasi, Uttar Pradesh, 221005, India

Location

Novartis Investigative Site

Bari, BA, 70124, Italy

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

Location

Novartis Investigative Site

Roma, RM, 00128, Italy

Location

Novartis Investigative Site

Orbassano, TO, 10043, Italy

Location

Novartis Investigative Site

George Town, Pulau Pinang, 10450, Malaysia

Location

Novartis Investigative Site

Kuching, Sarawak, 93586, Malaysia

Location

Novartis Investigative Site

Breda, North Brabant, 4818 CK, Netherlands

Location

Novartis Investigative Site

Leeuwarden, Provincie Friesland, 8934 AD, Netherlands

Location

Novartis Investigative Site

Breda, 4818 CK, Netherlands

Location

Novartis Investigative Site

Leeuwarden, 8934 AD, Netherlands

Location

Novartis Investigative Site

Porto, 4100-180, Portugal

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Barcelona, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28041, Spain

Location

Novartis Investigative Site

Bangkok, 10700, Thailand

Location

Novartis Investigative Site

Istanbul, Bagcilar, 34214, Turkey (Türkiye)

Location

Novartis Investigative Site

Diyarbakır, Sur, 21280, Turkey (Türkiye)

Location

Novartis Investigative Site

Istanbul, Turkey, 34214, Turkey (Türkiye)

Location

Novartis Investigative Site

Ankara, Yenimahalle, 06500, Turkey (Türkiye)

Location

Novartis Investigative Site

Ankara, 06500, Turkey (Türkiye)

Location

Novartis Investigative Site

Diyarbakır, 21000, Turkey (Türkiye)

Location

Novartis Investigative Site

Torquay, TQ2 7AA, United Kingdom

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

JDQ443

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2022
• First Posted: July 6, 2022
• Study Start: October 31, 2022
• Primary Completion: November 4, 2024
• Study Completion (Estimated): November 30, 2027
• Last Updated: April 21, 2026
• Results First Posted: October 9, 2025

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

BR (3); GR (1); US (1); IN (2); ES (3); CN (3); AR (4); BE (3); TU (6); AU (2); GB (1); NL (4); FR (5); TH (1); HU (1); MY (2); PT (1); DE (6); IT (4)