A phase Ib/II open-label, multi-center dose escalation study of JDQ443 in patients with advanced solid tumors harboring the KRAS G12C mutatio
- Conditions
- Advanced solid tumors harboring KRAS G12C mutation10027655
- Registration Number
- NL-OMON54361
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 45
Dose Escalation:
• Patients with advanced (metastatic or unresectable) KRAS G12C mutant solid
tumors who have received standard of care therapy or are intolerant or
ineligible to approved therapies.
Dose Expansion:
• Patients with advanced (metastatic or unresectable) KRAS G12C mutant
non-small cell lung cancer who have received a platinumbased chemotherapy
regimen and immune checkpoint inhibitor therapy, unless patient was ineligible
to receive such therapy. Treatment with a prior KRAS G12C inhibitor is not
allowed.
• Patients with advanced (metastatic or unresectable) KRAS G12C mutant
non-small cell lung cancer who have received a platinumbased chemotherapy
regimen and immune checkpoint inhibitor therapy, unless patient was ineligible
to receive such therapy, and one treatment line of a direct KRAS G12C inhibitor
given as a single agent and discontinued within 6 months of the first day of
study treatment.
• Patients with advanced (metastatic or unresectable) KRAS G12C mutant NSCLC
who have received a platinum-based chemotherapy regimen and an immune
checkpoint inhibitor therapy either in combination or in sequence, unless
patient was ineligible to receive such therapy. The patient must have at least
one untreated brain metastasis. Treatment with a prior KRAS G12C inhibitor is
not allowed.
• Patients with advanced (metastatic or unresectable) KRAS G12C mutant
colorectal cancer who have received standard-of-care therapy, including a
fluropyrimidine-, oxaliplatin-, and irinotecanbased chemotherapy, unless
patient was ineligible to such therapy. Treatment with a prior KRAS G12C
inhibitor is not allowed.
• Patients with advanced (metastatic or unresectable) KRAS G12C mutant solid
tumors other than NSCLC or CRC who have received standard of care therapy or
are intolerant or ineligible to approved therapies. Treatment with a prior KRAS
G12C inhibitor is not allowed.
All Patients:
• ECOG performance status of 0 or 1.
• Patients must have a site of disease amenable to biopsy and be a candidate
for tumor biopsy according to the institution*s own guidelines and requirements
for such procedures.
Tumors harboring driver mutations that have approved targeted therapies, with
the exception of KRAS G12C mutations.
• Prior treatment with a KRAS G12C inhibitor is excluded for patients in the
single agent dose escalation arm and a subset of groups in dose expansion.
• Prior treatment with a SHP2 or SOS1 inhibitor is not allowed for NSCLC
patients enrolled into the dose expansion parts of the JDQ443 single agent and
JDQ443 plus TNO155 expansion arms.
• Untreated brain metastases (applicable to all patients except the brain
metastasis group), symptomatic brain metastases (applicable to all patients),
or known leptomeningeal disease (applicable to all patients)
• Clinically significant cardiac disease or risk factors at screening
• Insufficient bone marrow, hepatic or renal function at screening
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>For all groups, Best Overall Response (BOR), Overall Response Rate (ORR),<br /><br>Duration of Response (DOR), Disease Control Rate (DCR), Progression Free<br /><br>Survival, (PFS) and Overall Survival (OS) per RECIST 1.1<br /><br><br /><br>For the brain metastasis group, Overall Intracranial Response Rate (OIRR),<br /><br>Intracranial Disease Crontrol Rate (IDCR), Best Overall Intracranial Response<br /><br>(BOIR), Duration of Intracranial Response (DOIR), and intracranial progression<br /><br>free survival (IPFS) per mRANO-BM.</p><br>
- Secondary Outcome Measures
Name Time Method <p>• Concentration and PK parameters of JDQ443, TNO155, and / or tislelizumab.<br /><br>• Incidence of antidrug antibodies to tislelizumab<br /><br>• Incidence and severity of adverse events and serious adverse events,<br /><br>including changes in laboratory values, electrocardiograms, and vital signs.<br /><br>• Frequency of dose interruptions, reductions, and dose intensity by treatment.<br /><br>• Incidence and severity of dose limiting toxicities (DLTs)(dose escalation<br /><br>only)</p><br>