This study has been transitioned to CTIS with ID 2024-511708-18-00 check the CTIS register for the current data. the Sponsor aims to investigate if JDQ443 will stop abnormal cell growth related to the marker KRAS G12C mutation in patients with NSCLC…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
- Respiratory tract neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Overall response rate (ORR), defined as the proportion of participants with a
confirmed complete response (CR) or partial response (PR) as best overall
response (BOR) per Response Evaluation Criteria in Solid Tumors version 1.1
(RECIST 1.1) by blinded independent review committee (BIRC).
Het primaire eindpunt van het onderzoek is ORR, gedefinieerd als de proportie
van deelnemers met een bevestigde CR/PR als BOR. BOR is gedefinieerd als de
beste respons geregistreerd vanaf het begin van de behandeling tot aan de
ziekte progressie per RECIST 1.1 door BIRC. CR en PR moeten worden bevestigd
door: herhaal beoordelingen die niet minder dan 4 weken moeten worden
uitgevoerd nadat voor het eerst aan de criteria voor respons was voldaan.
Gedocumenteerde reacties na het gebruik van een nieuwe antineoplastische
therapie zal worden beschouwd als:
non-respons.
Secondary outcome
• ORR per RECIST 1.1 by BIRC.
• DOR, defined as the time from the first occurrence of a PR or a CR per RECIST
1.1 by BIRC to the occurrence of disease progression or death due to any cause.
• PFS, defined as the time from the date of enrollment to the date of the first
documented disease progression per RECIST 1.1 by BIRC or date of death due to
any cause.
• OS, defined as the time from the date of enrollment to the date of death due
to any cause.
• Disease control rate (DCR), defined as the proportion of participants with a
BOR of confirmed CR, PR and stable disease (SD) per RECIST 1.1
by BIRC.
• Time to response (TTR), defined as the time from the date of enrollment to
the first documented response of either CR or PR per RECIST 1.1 by
BIRC.
• ORR, DOR, DCR, TTR and PFS per RECIST 1.1 by local radiology assessment.
• ORR, DOR, DCR and TTR per RECIST 1.1 by BIRC and by local radiology
assessment.
• PFS and OS
• Type, frequency and severity of adverse events, changes in laboratory values,
vital signs, electrocardiograms (ECGs).
• Concentration of JDQ443 in plasma and derived PK parameters, as appropriate.
• Time to definitive deterioration (TTD) in the NSCLC-SAQ total score, and TTD
in the physical functioning (PF) scale of the EORTC QLQ-C30
• Change from baseline to each treatment visit and EOT for NSCLC-SAQ total
score, pain, cough, dyspnea and items.
• Change from baseline to each treatment visit and EOT for all EORTCQLQ C30
domains, subscales and items
• Change from baseline to each treatment visit and to EOT for the FACT GP5
For the key secondary endpoint, ORR per RECIST 1.1 by BIRC in cohort B, the
same definition as in the Protocol, Section 9.3.1 applies.
Treatment with JDQ443 will be considered to have clinically relevant efficacy
in cohort B if an ORR of >= 40% is observed with the lower bound
of the 95% confidence interval >= 20%.
Background summary
This study investigates JDQ443 in patients with NSCLC who have a specific
change (*mutation*) in the DNA of the tumor cells. This mutation is called the
KRAS G12C mutation. The mutation is present in approximately 13% of all
patients with NSCLC and causes the tumor to grow faster. JDQ443 is a targeted
treatment that blocks the effects of the KRAS G12C mutation. This can cause the
growth of the tumor to be inhibited or come to a standstill.
Due to the targeted action of JDQ443 on the KRAS G12C mutation, only patients
with NSCLC and this mutation can participate in the study. During the
pre-selection it was determined that your tumor cells have this mutation.
In order to participate, one of the following must also be present: a small
amount (less than 1%) of the protein PD-L1 or an STK11 mutation. If either of
these properties is present, patients with NSCLC will benefit less from
immunotherapy. Immunotherapy is one of the commonly used treatments (*standard
treatments*) for NSCLC. During the pre-selection it was determined that your
tumor has one of the two characteristics.
JDQ443 has not yet been approved (*registered*) as a medicine by the Dutch
government. Doctors are not allowed to prescribe the drug to patients. JDQ443
can only be administered during a medical scientific examination. For
registration, research in patients is required. That is why your cooperation in
this research is requested.
Since August 2021, approximately 25 subjects with various cancers with a KRAS
G12C mutation have been treated with JDQ443. We don't know if the drug will
work for you. Your health may improve, deteriorate or not change during the
examination.
Study objective
This study has been transitioned to CTIS with ID 2024-511708-18-00 check the CTIS register for the current data.
the Sponsor aims to investigate if JDQ443 will stop abnormal cell growth
related to the marker KRAS G12C mutation in patients with NSCLC whose tumors
have specific characteristics, such as the presence of a KRAS G12C mutation, as
well as the presence of low levels of PD-L1 expression (cohort A) or an STK11
mutation (cohort B). The purpose of this study is to investigate if treatment
with JDQ443 will be efficacious and safe to control the growth of NSCLC in
study participants.
Study design
Open-label phase II study investigating the activity and safety of JDQ443 as a
sole drug for the first-line treatment of patients with locally advanced or
metastatic non-small cell lung cancer with a KRAS G12C mutation, with an
expression of PD-L1 less than 1% or a PD-L1 expression of 1% or more and a
STK11 co-mutation. This study will require approximately 120 subjects with
NSCLC from 24 different countries.
Intervention
treatment with JDQ443
Study burden and risks
Very common side effects (affecting more than 1 in 10 users) were: tiredness;
diarrhea, shortage of red blood cells (these cells transport oxygen through the
body, which can cause complaints such as fatigue (anemia)); fluid retention in
the extremities (arms and legs) (swelling); nausea; yield; pain in the joints
(arthralgia), increased levels of liver proteins in the blood (this may be a
sign of liver damage); pain in the muscles (myalgia); itch; reduced number of a
type of white blood cells called neutrophils (neutropenia); pain in the limbs;
lack of energy, physical weakness (asthenia).
Common side effects (affects less than 1 in 10 people): rash, signs of possible
damage to the pancreas/increased pancreatic values, increased skin reaction to
light (photosensitivity reaction), rash with both raised and flat skin lesions
(maculo-papular skin rash), signs of possible damage to the liver/increased
liver enzyme levels, skin condition with the presence of large and small
blisters filled with clear fluid (bullous dermatitis), swelling (edema).
Other potential side effects listed below are based on information collected
from laboratory and animal studies, as well as from clinical study data with
drugs that have a similar mechanism of action as JDQ443:
• Animal experiments have shown that JDQ443 can cause skin sensitization to
sunlight, therefore you may get sunburned more easily. It is important that you
avoid exposure to sunlight by limiting outdoor activities in sunlight, wearing
appropriate clothing and applying sunscreen [sunscreen that at least has a
protection factor of 15, includes ultraviolet A (UVA) and ultraviolet B (UVB)
protection, and is PABA free (PABA stands for para-aminobenzoic acid)]. It is
also advised to avoid use of sun lamp therapy and tanning bed (to avoid
artificial UV exposure).
• Changes in kidney function.
• Changes in adrenal gland function, including adrenal insufficiency with
symptoms such as tiredness (fatigue), muscle weakness, loss of appetite, upper
body obesity, high blood sugars, swelling of legs, skin problems (acne),
changes in blood pressure
• Side effects related to progesterone receptor inhibition, including menstrual
disorder, hemorrhage, and uterus pain.
• Side effects related to the heart and blood vessels (cardiovascular side
effects), such as abnormal heart rate and blood pressure.
• Side effects affecting your lungs, such as increased inflammation in your
lungs which could lead to cough and shortness of breath.
• Side effects affecting the female and male reproductive systems including the
ovaries, testes, epididymis and prostate gland, which could cause changes in
hormone levels or effects on fertility
Some side effects related to the eye and lung have been observed with drugs
that work similarly to JDQ443. Side effects related to the eye may include
retinal vein occlusion (RVO) where there is a blockage of the small veins that
carry blood away from the retina (the layer of tissue at the back of the inner
eye that converts light images to nerve signals and sends them to the brain),
reversible disease of the retina that results in vision changes and general
changes in vision.
Side effects related to lung includes interstitial lung disease (a type of
inflammation of lung tissue also called pneumonitis). It is important that you
alert your doctor of any signs of breathing difficulties (e.g., shortness of
breath, cough, fever) or new onset of cough while taking the study medication..
Problems or side effects that are not currently known could also occur,
including serious/severe side effects.
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
• Histologically confirmed locally advanced (stage IIIb/IIIc not eligible for
definitive chemoradiation or surgical resection with curative intent) or
metastatic (stage IV) NSCLC without previous systemic treatment for metastatic
disease. Prior (neo)adjuvant treatment with chemotherapy and/or immunotherapy,
or prior radiotherapy administered sequentially or concomitantly with
chemotherapy and/or immunotherapy for localized or locally advanced disease are
accepted if the time between therapy completion and enrollment is > 12 months.
• Presence of a KRAS G12C mutation (all participants) and:
• Cohort A: PD-L1 expression < 1%, regardless of STK11 mutation status
• Cohort B: PD-L1 expression >= 1% and an STK11 co-mutation
• At least one measurable lesion per RECIST 1.1.
• ECOG performance status <= 1.
• Participants capable of swallowing study medication.
Exclusion criteria
• Participants whose tumors harbor an EGFR-sensitizing mutation and/or ALK
rearrangement by local laboratory testing. Participants with other known
druggable alterations will be excluded, if required by local guidelines
• Previous use of a KRAS G12C inhibitor or previous systemic treatment for
metastatic NSCLC.
• A medical condition that results in increased photosensitivity (i.e. solar
urticaria, lupus erythematosus, etc).
• Known active central nervous system (CNS) metastases and/or carcinomatous
meningitis
• Participants who are taking a prohibited medication (strong CYP3A inducers)
that cannot be discontinued at least seven days prior to the first dose of
study treatment and for the duration of the study
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 | CTIS2024-511708-18-00 |
| EudraCT | EUCTR2022-001088-29-NL |
| ClinicalTrials.gov | NCT05445843 |
| CCMO | NL82042.028.22 |