JDQ443 for KRAS G12C NSCLC Brain Metastases

NCT05999357 | Withdrawn Phase 2 DMC

• 2 other identifiers: CJDQ443B1NL01T2023-505721-13-00
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this phase II clinical trial is to evaluate the intracranial efficacy of JDQ443, a KRAS G12C inhibitor in patients with KRAS G12C+ NSCLC and brain metastases (cohort A: asymptomatic, untreated brain metastases, cohort B: asymptomatic, treated brain metastases). The main question it aims to answer is to evaluate the intracranial efficacy, according to RANO-BM criteria, in patients with asymptomatic and untreated brain metastases. Participants will receive JDQ443 200 mg BID until unacceptable toxicity or disease progression.

Conditions

Non Small Cell Lung Cancer Metastatic; Brain Metastases, Adult; KRAS G12C

Keywords

non small cell lung cancer; brain metastases; KRAS G12C; JDQ443

Outcome Measures

Primary Outcomes (1)

• brain metastases overall response rate (ORR)

  ORR is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) based on central and local investigator's assessment according to RANO-BM criteria on brain MRI

  up to 24 months

Secondary Outcomes (9)

• brain metastases disease controle rate (DCR) (key secondary)

  up to 24 months

• CNS progression free survival (PFS) (key secondary)

  up to 24 months

• Extracranial ORR and DCR

  up to 24 months

• extracranial PFS

  up to 24 months

• overall PFS

  up to 24 months

Study Arms (1)

adult patients with KRAS G12C+ NSCLC and brain metastases

EXPERIMENTAL

Cohort A: adult patients with KRAS G12C+ NSCLC and untreated asymptomatic BM Cohort B: Adult patients with KRAS G12C+ NSCLC and treated asymptomatic BM JDQ443 200 mg BID until unacceptable toxicity or disease progression

Drug: JDQ443

Interventions

JDQ443 DRUG

JDQ443 tablets, orally administered

Also known as: no other name

adult patients with KRAS G12C+ NSCLC and brain metastases

Eligibility Criteria

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

You may qualify if:

• In order to be eligible to participate in this study, a subject must meet all of the following criteria:
• Signed informed consent must be obtained prior to participation in the study.
• Participant is an adult ≥ 18 years of age at the time of informed consent.
• ECOG performance status ≤2.
• Estimated life expectancy of 12 weeks or more
• Metastatic (stage IV) NSCLC with the presence of a KRAS G12C mutation (local test, tissue as well as liquid biopsy allowed) and untreated or progressing asymptomatic BM (cohort A) or treated and stable BM (cohort B).
• BM not in eloquent area (all patients have at least to be discussed with a neurologist, and preferably they are discussed in a neuro-oncology MDT). If treated with radiotherapy and stable, these patients are eligible for cohort B.
• Max BM size 2 cm in longest diameter (for each BM) for cohort A
• For cohort A: at least one untreated brain metastasis ≥ 5mm:
• Patients with largest measurable intracranial lesion ≥5 mm but \<10 mm may be allowed to enroll upon agreement with the principal investigator (for patients with target lesions of ≥ 5mm but \<10 mm, 1.5 mm slice thickness brain MRI is required).
• Prior local treatment is permissible if completed at least 14 days prior to study enrollment and provided unequivocal progression in the lesion has since occurred or if new lesions have occurred.
• For at least 7 days prior to first dose of JDQ443 in this study: Patient must be asymptomatic from CNS metastases and on a stable dose of corticosteroids, with a maximum of 4 mg dexamethasone/day. Anti-epileptic dose should also be stable for 7 days.
• Participant must have recovered from all toxicities related to prior treatments to grade ≤ 1 (CTCAE v 5.0). Exception to this criterion are alopecia and vitiligo of any grades.
• Adequate organ function including the following laboratory values at the screening visit:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (without growth factor support),

You may not qualify if:

• A potential subject who meets any of the following criteria will be excluded from participation in this study:
• Leptomeningeal metastasis (based on MRI or CSF cytology, if strong suspicion despite negative MRI, CSF analysis should be done)
• Previous treatment with KRAS G12C inhibitor except if ≥ 1 year has elapsed since last dose
• Tumors harbouring other oncogenic drivers for which targeted therapy is available (note: patients with KRAS G12C mutation as a resistance mechanism on for example EGFR or ALK inhibitors are not eligible).
• History of severe hypersensitivity reaction to JDQ443 or its excipients.
• History of allogeneic bone marrow or solid organ transplant
• Participant has had major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within 4 weeks prior to starting study treatment or has not recovered from side effects of such procedure.
• Thoracic radiotherapy to lung fields ≤ 4 weeks prior to starting the study treatment or participants who have not recovered from radiotherapy-related toxicities. For all other anatomic sites (including radiotherapy to thoracic vertebrae and ribs) radiotherapy ≤ 2 weeks prior to starting the study treatment or has not recovered from radiotherapy-related toxicities. Palliative radiotherapy for bone lesions ≤ 2 weeks prior to starting study treatment is allowed.
• Clinically significant, uncontrolled cardiac disease and/or recent cardiac events (within 6 months), such as:
• Unstable angina or myocardial infarction within 6 months prior to screening.
• Symptomatic congestive heart failure (defined as New York Heart Association Grade II or greater).
• Documented cardiomyopathy.
• Clinically significant cardiac arrhythmias (e.g. sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker)
• Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 160 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 100 mm Hg, unless controlled prior to first dose of study treatment.
• History or current diagnosis of ECG abnormalities indicating significant risk of safety for study participation such as: concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker.

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Novartis: collaborator

MeSH Terms

Conditions

Brain Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

JDQ443

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Lizza Hendriks, MD, PhD

  Maastricht University Medical Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single arm, open-label, 2-cohort phase II study. Cohort A: asymptomatic, untreated BM, Cohort B: asymptomatic, treated BM.

Study Record Dates

• First Submitted: August 2, 2023
• First Posted: August 21, 2023
• Study Start: April 15, 2024
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2028
• Last Updated: May 29, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share