Study of JDQ443 in Comparison With Docetaxel in Participants With Locally Advanced or Metastatic KRAS G12C Mutant Non-small Cell Lung Cancer

Sponsor: Novartis Pharmaceuticals

Sponsor score: 60

ClinicalTrials ID:NCT05132075

This Phase III trial compares JDQ443 tablets to intravenous docetaxel in adults with advanced KRAS G12C mutant NSCLC post-platinum and immune checkpoint therapies. Participants can cross over to JDQ443 upon progression. Eligibility includes confirmed KRAS G12C mutation and prior treatments. Approximately 360 participants will be randomized 1:1.

Patient Parameters

Program Overview

This is a phase III randomized open label study designed to compare JDQ443 as monotherapy to docetaxel in participants with advanced non-small cell lung cancer (NSCLC) harboring a KRAS G12C mutation who have been previously treated with a platinum-based chemotherapy and immune checkpoint inhibitor therapy either in sequence or in combination.

Description

The study has been designed as a Phase III trial and consists of 2 parts:

  • Randomized part will evaluate the efficacy and safety of JDQ443 as monotherapy in comparison with docetaxel. Participants randomized to docetaxel arm will have the opportunity to cross-over to JDQ443 at disease progression per RECIST 1.1 confirmed by BIRC.
  • Extension part will be open after final progression-free survival (PFS) analysis (if the primary endpoint has met statistical significance) to allow participants randomized to docetaxel treatment to crossover to receive JDQ443 treatment regardless of progression on docetaxel.

The study population will include adult participants with locally advanced or metastatic (stage IIIB/IIIC or IV) KRAS G12C mutant non-small cell lung cancer (by tissue or plasma as determined by a Novartis-designated central laboratory or accepted local tests) who have received prior platinum-based chemotherapy and prior immune checkpoint inhibitor therapy administered either in sequence or as combination therapy.

Approximately 360 participants will be randomized to JDQ443 or docetaxel in a 1:1 ratio stratified by prior line of therapy and ECOG performance status.

Eligibility Criteria

Inclusion Criteria

  • Participant has histologically confirmed locally advanced/metastatic (stage IIIB/IIIC or IV)
  • Participant has a KRAS G12C mutation present in tumor tissue or plasma prior to enrollment, as determined by a Novartis designated central laboratory or by accepted local tests.
  • Participants has received one prior platinum-based chemotherapy regimen and one prior immune checkpoint inhibitor therapy for locally advanced or metastatic disease
  • Participant has at least 1 evaluable (measurable or non-measurable) lesion by RECIST 1.1 at the screening visit.

Exclusion Criteria

  • Participants who have previously received docetaxel (except if received in neoadjuvant or adjuvant setting with no progression within 12 months after the of end of treatment), or any other KRAS G12C inhibitor.
  • Participant has EGFR-sensitizing mutation and/or ALK rearrangement by local laboratory testing. Participants with other druggable alterations will be excluded if required by local guidelines.
  • Participant has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Participant has an history of interstitial lung disease or pneumonitis grade > 1.

Other inclusion/exclusion criteria may apply

Locations

FACILITYZIPCITYSTATE
Valley Medical Center Research98055RentonWashington

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