This study has been transitioned to CTIS with ID 2023-508073-87-00 check the CTIS register for the current data. Primary objectives:Dose Escalation• To assess the safety and tolerability of JDQ443 single agent and JDQ443 in combination with TNO155,…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
For all groups, Best Overall Response (BOR), Overall Response Rate (ORR),
Duration of Response (DOR), Disease Control Rate (DCR), Progression Free
Survival, (PFS) and Overall Survival (OS) per RECIST 1.1
For the brain metastasis group, Overall Intracranial Response Rate (OIRR),
Intracranial Disease Crontrol Rate (IDCR), Best Overall Intracranial Response
(BOIR), Duration of Intracranial Response (DOIR), and intracranial progression
free survival (IPFS) per mRANO-BM.
Secondary outcome
• Concentration and PK parameters of JDQ443, TNO155, and / or tislelizumab.
• Incidence of antidrug antibodies to tislelizumab
• Incidence and severity of adverse events and serious adverse events,
including changes in laboratory values, electrocardiograms, and vital signs.
• Frequency of dose interruptions, reductions, and dose intensity by treatment.
• Incidence and severity of dose limiting toxicities (DLTs)(dose escalation
only)
Background summary
Better treatments are needed for patients harboring the KRAS G12C mutation.
JDQ443 is a potent and selective inhibitor of mutant KRAS G12C, which is a
common driver of oncogenic signaling in a number of different types of tumors.
Targeted inhibition of KRAS G12C via JDQ443 may result in robust antitumor
responses.
Study objective
This study has been transitioned to CTIS with ID 2023-508073-87-00 check the CTIS register for the current data.
Primary objectives:
Dose Escalation
• To assess the safety and tolerability of JDQ443 single agent and JDQ443 in
combination with TNO155, JDQ443 in combination with tislelizumab, and JDQ443 in
combination with TNO155 and tislelizumab, and to identify the maximum tolerated
dose and/or recommended dose and regimen for future studies.
Dose Expansion
• To evaluate the overall response rate (ORR) for JDQ443 single agent and
JDQ443 in combination with TNO155, JDQ443 in combination with tislelizumab, and
JDQ443 in combination with TNO155 and tislelizumab.
• To evaluate the preliminary overall intracranial response rate (OIRR) of
JDQ443 single agent (brain metastasis group only)
• To evaluate the preliminary safety/tolerabilityand anti-tumor activity of
JDQ443 single agent in patients with NSCLC (JDQ443 dose randomization group
only)
Secondary objectives:
To evaluate the anti-tumor activity of the study treatments.
• To further characterize the safety and tolerability of the study treatments
(dose expansion part only).
• To characterize the PK of JDQ443 single agent and PK of JDQ443, TNO155, and
tislelizumab in JDQ443 in combination with TNO155, JDQ433 in combination with
tislelizumab and JDQ443 in combination with TNO155 and tislelizumab
• To evaluate the immunogenicity of tislelizumab when dosed in combination with
JDQ443 and / or TNO155.
• To evaluate the intracranial preliminary anti-tumor activity of JDQ443 single
agent (brain metastasis group only)
A food effect cohort will be done to examine the influence of medication intake
when patient hasn't eaten versus when the patient has had food prior to intake
of medication.
Study design
This is a phase Ib/II open label study. The escalation part will characterize
the safety and tolerability of JDQ443 single agent and JDQ443 in combination
with the other study treatments (TNO155 and tislelizumab) in advanced solid
tumor patients. After the determination of the maximum tolerated dose /
recommended dose for a particular treatment arm, dose expansion will assess the
anti-tumor activity and further assess the safety, tolerability, and PK/PD of
each regimen at the maximum tolerated dose / recommended dose.
Intervention
JDQ443, tislelizumab (VDT482), TNO155
Study burden and risks
Risks and side-effects associated with the treatment provided. Risks associated
with the study assessments suchs as blooddraws, imaging and tumor biopsy.
Burdens: 3 week cycles, cycle 1: 4 visits, cycle 2 & 3: 3 visits, from C4
onwards 1 visit per cycle. Assessments during visits, depending on mono- or
combination therapy and type of visit: physical exam, blooddraws, ECGs / vital
signs, imaging, pregnancy testing, tumor biopsy.
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
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.
Exclusion criteria
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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-508073-87-00 |
| EudraCT | EUCTR2020-004129-22-NL |
| ClinicalTrials.gov | NCT04699188 |
| CCMO | NL75349.031.21 |