NCT05999357

JDQ443 for KRAS G12C NSCLC Brain Metastases

A Phase II Study evaluaTing intRacranial effIcacy of JDQ443 in patiEnts With KRAS G12C+ NSCLC and bRain Metastases

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Maastricht University Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

In the past decade, the treatment and prognosis of patients with metastatic non-small cell lung cancer (NSCLC) has significantly improved, due to new systemic treatments (i.e. intravenous or oral therapy). NSCLC is increasingly subtyped based on the presence of certain mutations in the NSCLC for which targeted therapies have become available. KRAS G12C is the most commonly found mutation, and recently oral therapies (sotorasib in the EU and USA, adagrasib in the USA) have become available. Brain metastasis (BM) incidence in patients with KRAS G12C+ non-small cell lung cancer (NSCLC) is high, but unfortunately, except for one small trial with adagrasib, patients with BM were excluded from most clinical trials with KRAS G12C inhibitors. Furthermore, sotorasib is not very well able to reach the central nervous system (CNS). Adagrasib can penetrate into the CNS, but this comes with relevant treatment related toxicity (mainly gastro-intestinal and liver). JDQ443 is a new oral KRAS G12C inhibitor, that preclinically has the same ability as adagrasib to reach the CNS, but based on small series seems to have less toxicity. As toxicity seems favourable for JDQ443 compared with sotorasib and adagrasib, and as preclinically, CNS penetration seems comparable to adagrasib, data regarding the efficacy of JDQ443 on BM is urgently needed. Therefore the main objective of this trial is to evaluate the intracranial efficacy of JDQ443 in patients with KRAS G12C+ NSCLC and asymptomatic untreated BM. Furthermore, there will be an exploratory cohort for patients with asymptomatic and treated BM. The intervention consists of JDQ443 200 mg BID until unacceptable toxicity or disease progression.

Conditions

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

Interventions

Type	Name	Description
DRUG	JDQ443	JDQ443 tablets, orally administered

Timeline

• Start date: 2024-04-15
• Primary completion: 2027-08-01
• Completion: 2028-08-01
• First posted: 2023-08-21
• Last updated: 2024-05-29