This study has been transitioned to CTIS with ID 2024-513412-10-00 check the CTIS register for the current data. Phase 1: • To determine the MTD/RP2D regimen of brigatinib monotherapy when administered in pediatric and AYA patients with ALK+ ALCL or…
ID
Source
Brief title
Condition
- Other condition
- Leukaemias
Synonym
Health condition
ALK+ ALCL, IMT en andere ALK+ tumoren
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Phase 1:
• Dose-limiting toxicities (DLTs) during the first course of therapy.
• Brigatinib plasma PK parameters to be determined:
o maximum observed concentration (Cmax),
o time of first occurrence of maximum observed concentration (Tmax),
o area under the concentration-time curve from time 0 to the time of the last
quantifiable concentration (AUClast).
• The RP2D will be selected by the DSMB and will be based on the dose that
results in equivalent (approximately ±20% of the adult values) PK exposure to
the adult comparator and with <2 out of 6 patients at this dose level present
with a DLT and taking into account responses observed in phase 1.
Phase 2:
In Cohort B1, ALK+ IMT :
• Overall response rate (ORR), defined as the percentage of patients with CR or
PR according to RECIST 1.1 after 1 course and best ORR during brigatinib
treatment.
In Cohort B2, ALK+ ALCL:
• EFS (using the IPNHL response criteria), defined as the time between start of
study treatment and first event being progressive disease, relapse, death of
any cause and second malignancies, whatever happens first. Patients
consolidated with HSCT will be censored.
Secondary outcome
Phase 1:
Safety
• Adverse events (AEs), as characterized by type, frequency, severity (graded
using CTCAE v5.0), including ocular, pulmonary, endocrine AEs, and height,
weight or growth abnormalities, timing and relation to the study therapy,
during the first and subsequent courses of therapy.
• Occurrence of toxic death, i.e. death attributable to brigatinib therapy, as
well as other causes of death.
• Laboratory abnormalities as characterized by type, frequency, severity and
timing.
• The cumulative incidence of non-relapse mortality, with time calculated
between start of study treatment and death.
• Palatability questionnaire during two years of treatment (for frequency see
SOE table).
• Acceptability: diary reporting number of times a dose was not effectively
administered.
• Occurrence of any long-term toxicity during the off-therapy period up to 5
years after study inclusion with special attention to ocular, pulmonary,
endocrine AEs, and height, weight or growth abnormalities .
• Collection of grade 3 or higher AEs and AESIs, suspected by the investigator
to be related to brigatinib after the start of new anticancer therapy.
Activity/efficacy
• ORR, defined as CR or PR, by RECIST 1.1 for solid tumors (other than
neuroblastoma or brain tumors), by IPNHL (International Pediatric revised
Response Criteria for Malignant Lymphoma) for ALCL, by NANT (New Approaches to
Neuroblastoma Therapy) response criteria for neuroblastoma, by RANO (Responses
Assessment in Neuro-Oncology) criteria for brain tumors, measured after 1
course and as best response during brigatinib treatment,
• Time to best response, defined as the time between achieving the best
response and the start of treatment with brigatinib For patients with ALCL;
qualitative minimal residual disease (MRD) measured at multiple timepoints
during treatment, including the percentage of patients who become MRD-negative,
and time to MRD negativation.
• Cumulative incidence of non-response or relapse and/or non-relapse mortality
or patient withdrawal due to side effects in a competing risk model.
• Duration of response (DOR), defined as the time between achieving response
(CR or PR) after starting study treatment and documented disease progression,
relapse or death.
• EFS, defined as the time between start of study treatment and first event:
relapse, progressive disease, death of any cause and second malignancies,
whichever happens first.
• OS, defined as time to death following start of study treatment.
• Number of patients with IMT that undergo a complete (microscopic radical R0)
resection after treatment with brigatinib.
• Comparison of survival estimates for ALCL patients consolidated with SCT with
patients that did not receive consolidation for SCT, and describe response
versus duration of MRD negativity..
• ORR, defined as CR or PR, (by IPNHL), measured after 1 course and as best
response during brigatinib treatment (re-induction) in patients with ALCL that
relapse after brigatinib discontinuation and that are subsequently
re-challenged with brigatinib.
• Number and percentage of IMT patients with completely necrotic tumors by
pathology evaluation.
• Duration of on treatment survival, defined as time from first treatment date
to disease progression, death, or discontinuation of treatment for any reason
(e.g., toxicity, patient/physician preference, or initiation of a new treatment
without documented progression, usingapplicable response criteria as specified
in section 11).).
Phase 2 :
Safety (in both cohorts)
• Adverse events (AEs), as characterized by type, frequency, severity (graded
using CTCAE v5.0), including pulmonary, ocular, endocrine AEs and height,
weight or growth abnormalities, timing and relation to the study therapy,
during brigatinib treatment.
• Occurrence of toxic death, i.e. death attributable to brigatinib therapy as
well as other causes of death.
• Laboratory abnormalities as characterized by type, frequency, severity and
timing.
• The cumulative incidence of non-relapse mortality, defined as the cumulative
probability of non-relapse mortality, with time calculated between start of
study treatment and death.
• Palatability questionnaire during two years of treatment (for frequency see
SOE table).
• Acceptability: diary reporting number of times a dose was not effectively
administered.
• Brigatinib plasma PK parameters
o maximum observed concentration (Cmax),
o time of first occurrence of maximum observed concentration (Tmax),
o area under the concentration-time curve from time 0 to the time of the last
quantifiable concentration (AUClast).
• Occurrence of any long-term toxicity during the off-therapy period up to 5
years after study inclusion) with special attention pulmonary, ocular,
endocrine AEs and height, weight or growth abnormalities.
• Collection of grade 3 or higher AEs and AESIs, suspected by the investigator
to be related to brigatinib after the start of new anticancer therapy.
Activity/efficacy
In Cohort B1, ALK+ IMT:
• Time to best response, defined as the time between achieving the best
response and the start of treatment with brigatinib.
• Duration of response (DOR), defined as the time between achieving response
(CR or PR according to RECIST 1.1) after starting study treatment and
documented relapse or death.
• The number of IMT patients that undergo a (curative) resection after
treatment with brigatinib.
• Cumulative incidence of non-response or relapse and/or non-relapse mortality
or patient withdrawal due to side effects in a competing risk model.
• Number of patients relapsing after electively stopping brigatinib after 24
cycles of brigatinib therapy, and to report the 1 and 2 year cumulative
incidence of relapse after stopping brigatinib in these patients.
• EFS (using RECIST criteria), defined as the time between start of study
treatment and first event: relapse, progressive disease, death of any cause and
second malignancies, whichever happens first.
• OS, defined as time to death of any cause following start of study treatment.
• Duration of on treatment survival, defined as time from first treatment date
to disease progression, death, or discontinuation of treatment for any reason
(e.g., toxicity, patient preference, or initiation of a new treatment without
documented progression, using RECIST 1.1 criteria).
• Number and percentage of IMT patients with completely necrotic tumors by
pathology evaluation
In Cohort B2, ALK+ ALCL:
• ORR, defined as CR or PR, by IPNHL, measured after 1 course and as best
response during brigatinib treatment.
• Time to best response, defined as the time between achieving the best
response and the start of treatment with brigatinib.
• Duration of response (DOR), defined as the time between achieving response
(according to IPNHL) after starting study treatment and documented relapse or
death.
• Cumulative incidence of non-response or relapse and/or non-relapse mortality
or patient withdrawal due to side effects in a competing risk model.
• Number of patients relapsing after electively stopping brigatinib after 24
cycles of brigatinib therapy, and to report the 1 and 2 year cumulative
incidence of relapse after stopping brigatinib in these patients.
• OS, defined as time to death of any cause following start of study treatment.
• Duration of on treatment survival, defined as time from first treatment date
to disease progression, death, or discontinuation of treatment for any reason
(e.g., toxicity, patient preference, or initiation of a new treatment without
documented progression, using IPNHL response criteria.
&bul
Background summary
Brigatinib is a second generation novel, orally administered, tyrosine kinase
inhibitor (TKI) that potently inhibits activated variants of ALK and to a
lesser extent ROS1. Currently, brigatinib is approved by FDA and EMA as a
treatment for adult patients with locally advanced or metastatic ALK+ non-small
cell lung cancer (NSCLC), both in ALK inhibitor naïve patients as well as after
previous treatment with crizotinib. Brigatinib is well tolerated in adults at
the recommended flat fixed dose of 180 mg QD, with a 7-day lead-in of 90 mg QD.
Compared to some other ALK-inhibitors, it has a more favorable safety profile
and it penetrates into the CNS. Recently, crizotinib was approved by the FDA
for pediatric and young adult patients with ALCL. In Europe, there are
currently no ALK inhibitors registered for children, and besides brigatinib
there are no other ALK inhibitors (that we are aware of) with a pediatric
investigational plan (PIP) approved with a focus on ALCL and IMT. Adult studies
in patients with NSCLC have shown that brigatinib is more potent than
crizotinib, can overcome resistance mutations that crizotinib cannot overcome,
and has superior intracranial efficacy over crizotinib for treating NSCLC brain
metastases due to the CNS penetration.
Apart from NSCLC, ALK is rearranged, mutated, or amplified in a variety of
tumors relevant to the pediatric population including neuroblastoma, IMT,
infants with brain tumors and ALCL. Although IMTs can also harbor ROS1
rearrangements, ROS1 is less sensitive to brigatinib than ALK, and therefore
ROS1 rearranged IMTs will not be eligible for this study. Other, potentially
more potent ROS1 inhibitors, are currently in development in pediatric
malignancies.
IMT is a very rare solid tumor characterized by spindle-shaped myofibroblastic
cells with a chronic inflammatory component that mostly occurs in children and
adolescents, primarily in the lung, soft tissues, and the abdominal region.
Chromosomal translocations leading to ALK activation are present in 50% to 70%
of IMTs, and are more common at younger ages. IMT treatment is generally
limited to surgical resection, and there are no standard approaches for
metastatic/recurrent disease or when complete resection is deemed not feasible
or may result in (severe) mutilation.
ALCL is a rare form of non-Hodgkin lymphoma (NHL) that occurs predominantly in
children, adolescents, and young adults (AYA). ALCL is characterized by
proliferation of lymphoid T cells that express CD30. Up to 90% of children with
ALCL have ALK+ disease, whereas adult ALCL patients exhibit ALK positivity less
frequently (50%). ALK+ ALCL is a chemo sensitive disease but 20-40% of the
patients still suffer from relapse. The standard of care (SOC) for patients
with recurrent ALCL comprises reinduction chemotherapy followed by
hematopoietic stem cell transplantation (HSCT), with subsequent high risk of
treatment-related morbidity and mortality, and with poor results. ALK
inhibitors in this relapse setting could potentially improve outcome for these
patients and, with two year of treatment, achieve deep CR, replacing the need
for consolidation with HSCT and thereby reducing treatment-related morbidity
and mortality induced by HSCT. More recently , another group of very high-risk
ALCL patients was identified: patients with persistent positive MRD (by
qualitative assessment) after the first chemotherapy course were shown to have
an inferior prognosis with a 5-year event free survival (EFS) of ~20%. To date,
there is no strategy to improve outcome of these very high risk patients and
avoid relapse by alternative treatment regimens.
The present study evaluates the safety and efficacy of brigatinib monotherapy
in pediatric and young adult patients with ALK+ ALCL, IMT or other solid
tumors. The robust clinical efficacy of brigatinib observed in adult patients
with ALK+ NSCLC, the promising proof-of-concept data available in the
literature with use of other ALK inhibitors in ALK+ IMT and ALCL patients and
the unmet medical needs described above, provide a scientific rationale to
explore use of brigatinib in these cancers. There is currently no ALK inhibitor
recommended by the European Medicines Agency (EMA) in the European
Union/European Economic Area for use in paediatric patients and brigatinib has
a clear advantage as opposed to crizotinib (only other ALK inhibitor approved
by FDA for ALCL in children and young adults), being more potent and
penetrating the CNS. Overlap within the ITCC portfolio, with the other
ALK-inhibitors studies is limited, where the other ALK inhibitors mainly focus
on other disease indications, such as brain tumors or ROS-mutated tumors.
Study objective
This study has been transitioned to CTIS with ID 2024-513412-10-00 check the CTIS register for the current data.
Phase 1:
• To determine the MTD/RP2D regimen of brigatinib monotherapy when administered
in pediatric and AYA patients with ALK+ ALCL or ALK+ solid tumors, including
ALK+ IMT.
• To characterize the PK of brigatinib administered as monotherapy in pediatric
and AYA patients with ALK+ ALCL or ALK+ solid tumors, including ALK+ IMT.
Note that:
o If the MTD is not reached at the highest proposed test dose, no further
dose-escalation will be performed.
o Pediatric PK data, compared to exposure in adults, will be taken into
consideration to determine the RP2D.
Phase 2:
• Cohort B1, ALK+ IMT:
To establish the anti-tumor activity of single agent brigatinib when
administered to children with ALK+ IMT.
• Cohort B2, ALK+ ALCL:
To establish the efficacy of single agent brigatinib when administered to
children with ALK+ ALCL without planned HSCT in consolidation.
Study design
This is an open-label, phase I-II dose-escalation and expansion study designed
to define the recommended dose of brigatinib as monotherapy in pediatric and
young adult patients with ALK+ ALCL, IMT or other solid tumors, and to evaluate
the pharmacokinetics (PK), (long-term) safety and efficacy of brigatinib in
these children.
Phase 1 will be a dose escalation study using a rolling six design, aiming to
accrue a minimum of 6 and a maximum of 18 evaluable patients. Dose levels are
given in the table below. Only patients >=1 and <18 years will be eligible for
phase 1.
Phase 2 will be the tumor cohort expansion part of the study to further
evaluate the safety, tolerability, and clinical activity/efficacy of brigatinib
as monotherapy in two tumor-specific cohorts:
• Cohort B1: ALK+ IMT
The planned sample size for Phase 2 is 28 patients with IMT. Patients who are
included in the monotherapy Phase 1 IMT dose-escalation portion of the study
treated at the RP2D will count towards the total sample size of 28 patients. At
least 15 patients younger than 18 years of age (with a total of at least 28
patients) need to be evaluable for the primary analysis.
• Cohort B2: ALK+ ALCL
The planned sample size for Phase 2 is 22 patients with ALCL. Patients who are
included in the monotherapy Phase 1 ALCL dose-escalation portion of the study
and treated at the RP2D will count towards the total sample size of 22
patients. At least 11 patients younger than 18 years of age (with a total of at
least 22 patients) need to be evaluable for the primary analysis.
Intervention
Brigatinib will be administered orally in 28-day cycles continuously at the
assigned dose level in Phase 1 and the RP2D in Phase 2 and dosed based on body
weight. Brigatinib may be taken with or without food. Each tablet should be
swallowed separately with a sip of water. At initiation, the treatment begins
by a lead-in phase of seven days with a decreased dose of brigatinib to
minimize the risk of early pulmonary toxicity as described in NSCLC in adults.
Brigatinib is available as a tablet(s) of 30 mg, 90 mg and 180 mg. At a later
stage an age appropriate (liquid) formulation will be made available for
younger children/those who cannot swallow tablets and added to this protocol by
an amendment. The tablets cannot be crushed or given via a nasogastric tube.
Duration of treatment:
Patients with ALCL who completed the initial 24 cycles of treatment and, in the
opinion of the investigator and confirmed by the sponsor, continue to
experience a clinically meaningful benefit from brigatinib, may continue to
receive brigatinib treatment on protocol, until a total of 24 cycles of
continued MRD-negativity while on brigatinib treatment. In ALCL, continuation
of treatment for 24 cycles after complete molecular remission (i.e. qualitative
MRD negativation) is strongly advised before discontinuation of brigatinib
treatment.
Patients with IMT or other solid tumor who have met the primary (and/or second
endpoints of the study and in the opinion of investigator and confirmed by the
sponsor, and continue to experience a clinical benfit may continue to receive
brigatinib in an extension phase of this study, or a separate open-label
rollover study, or through another appropriate access process. Follow-up of
these patients shall be organized as per standard of care procedures.
Patients who relapsed after stopping brigatinib, may continue to receive
brigatinib in an extension phase of this study, or a separate open-label
rollover study, or through another appropriate access process. Follow-up of
these patients shall be organized as per standard of care procedures.
Study burden and risks
Risks of study participation mainly involve the potential side effects of
brigatinib treatment. Previous (adult) studies have shown that brigatinib is
relatively safe. Of special interest is the pneumonitis related to brigatinib
treatment that has been described in adults with NSCLC. However, with the
introduction of a 7 day lead-in phase, pneumonitis has become less frequent and
mostly less severe. The side effects of brigatinib should be weighted against
the risks of the currently available treatments. New side-effects may still
appear as the number of patients treated with brigatinib is still limited and
there is no experience in children yet.
IMT patients currently have no standardized systemic treatment. Surgery is the
mainstay of treatment but due to close relation to vital structures or due to
its infiltrating nature, a radical resection is often not possible without
clinically relevant mutilation. Previously, ALK inhibitors have shown to be
very effective in ALK+ IMT patients, but currently no ALK inhibitors are
approved or available for treatment of IMT patients.
For patients with ALCL, CR achieved with re-induction treatment at relapse is
often consolidated with allo-HSCT. As described previously, transplantation can
be toxic, with treatment-related morbidity and mortality, with a mortality rate
still around 10%. Like with IMT patients, previous ALK inhibitors have shown to
be effective in patients with ALK+ ALCL patients, but until now, no ALK
inhibitors are approved or available for treatment of pediatric ALCL patients
in Europe. In the current study, it is recommended to avoid consolidation with
allo-HSCT, with the rationale that early introduction of an ALK inhibitor
combined with longer (two year) treatment may achieve deeper CR and may defer
the need for allo-HSCT. Nevertheless, withholding consolidation with
transplantation carries the risk of more patients relapsing upon treatment
discontinuation. On the other hand, it has been observed that patients that do
relapse after stopping treatment with ALK inhibitors remain sensitive for ALK
inhibition when treatment is resumed, and could achieve a new CR.The cumulative
incidence of relapse for patients not receiving HSCT will therefore be
monitored closely within this study; including the response to re-exposure with
brigatinib for patients that relapsed after treatment discontinuation. We
therefore consider it justifiable to attempt to withhold HSCT as standard
consolidation after 2 years of brigatinib therapy in the context of this study,
with the aim to asses whether 2 years of TKI treatment may lead to continued
complete remissions without HSCT. To mitigate risks, this study will include a
safety stopping rule for ALCL patients to monitor the number of patients that
relapse after brigatinib discontinuation.
Taking together, given the high medical need including the poor response for
patients with relapsed/refractory ALCL and IMT, and the risk of surgical
mutilation in IMTs that cannot be easily resected, we consider that the
potential benefit of brigatinib outweighs the potential risks for this specific
patient population.
Heidelberglaan 25
Utrecht 3584 CS
NL
Heidelberglaan 25
Utrecht 3584 CS
NL
Listed location countries
Age
Inclusion criteria
1. Patients must be >=1 and < 26 years of age at the time of enrollment, and
able to swallow brigatinib tablets
Note 1: for phase 1 only patients < 18 years old will be eligible, note a
liquid formulation for children who cannot swallow tablets is in development.
Note 2: for the Netherlands only, minimum age is >= 5 years.
Note 3: for the Czech Republic only, minimum age is >= 4 years.
2. Patients must have a histologically confirmed diagnosis of cancer at baseline
3. Patients are required to provide prior results showing an activating ALK
aberration in the tumor per local laboratory results, and material needs to be
available for central laboratory confirmation of ALK status
4. For Phase 1:
• Patients with ALCL must be relapsed/refractory or intolerant to standard
therapies. Refractory disease for ALCL is defined as:
o no response to at least one course of ALCL99/other standard of care
chemotherapy (SD or PD ), and/or
o MRD-positivity by qualitative PCR for NPM-ALK after at least one course
ALCL99/other standard of care chemotherapy (before the second course of
chemotherapy).
• Patients with relapsed/refractory (R/R) or newly diagnosed IMT must not be
suitable for curative surgical resection without causing severe mutilation or
risk associated with organ involvement, or have metastatic disease.
• Patients with other solid tumors (excluding IMT) must have relapsed or
refractory disease .
• Only patients >=1 and < 18 years will be eligible for phase 1. For the
Netherlands only, minimum age is >= 5 years
5. For Phase 2, patients must have measurable and/or evaluable disease:
• Patients with ALCL must be relapsed/refractory as defined.
o No response to at least one course of ALCL99/other standard of care
chemotherapy (SD or PD), and/or
o MRD-positivity by qualitative PCR for NPM-ALK after at least one course of
ALCL99/other standard of care chemotherapy (before the second course of
chemotherapy).
• Patients with R/R IMT Relapsed/refractory IMT, or newly diagnosed, including
locally advanced and metastatic IMT which cannot be surgically resected without
causing mutilation.
6. Performance Status:
• Karnofsky performance status >=40% for patients >=16 years of age or Lansky
Play Scale >=40% for patients <16 years of age for ALCL patients in phase 2.
• Karnofsky performance status >=50% for patients >=16 years of age or Lansky
Play Scale >=50% for patients <16 years of age, for IMT and other solid tumors
and for ALCL patients in phase 1.
7. Patients must not be receiving other investigational medications within 30
days of first dose of study drug or while on study.
9. Patients must have recovered to Grade <2 NCI CTCAE v5.0 or to baseline, from
any nonhematologic toxicities
10. Patients must meet the organ function and system function requirements as
stated below:
• Patients must have adequate renal and hepatic function
• No clinical, radiological or laboratory evidence of pancreatitis
• Absolute neutrophil count: >=0.75 × 10 9/L, except in case of macrophage
activation syndrome (MAS) or bone marrow involvement.
• Platelet count
o In phase 1: Platelet count: >=75 × 10^9/ L, except in case of MAS or bone
marrow involvement
o In phase 2: : Platelet count: >=75 × 10^9/ L, except in case of MAS or bone
marrow involvement. For patients post SCT, platelet count >=50 × 10^9/ L is
accepted.
o Hemoglobin >=8 g/dL or 5.0 mmol/L (red blood cell [RBC] transfusions to
achieve this value are allowed
13. Have a life expectancy of >=3 months.
14. Female patients of childbearing potential must have a negative urine or
serum pregnancy test confirmed prior to enrollment.
16. Contraception:
• Male and female patients of child-bearing potential must agree to use, an
acceptable effective method for male and highly effective method for female
Remaining Inclusion criteria : see protocol
Exclusion criteria
1. Patients receiving systemic treatment with strong or moderate CYP3A
inhibitors or inducers within 14 days or five half-lives, whichever the less,
prior to the first dose of study drug (refer to Section 5.2 for a list of
example medications).
2. Diagnosis of another concurrent primary malignancy.
3. Clinically significant cardiovascular disease, including any of the
following:
• Myocardial infarction or unstable angina within 6 months of study entry.
• History of or presence of heart block, and/or clinically significant
ventricular or atrial arrhythmias.
• Uncontrolled hypertension defined as persistent elevation of systolic and/or
diastolic blood pressures to >=95th percentile based on age, sex, and height
percentiles despite appropriate antihypertensive management.
4. Planned non-protocol chemotherapy, radiation therapy, another
investigational agent, or immunotherapy while patient is on study treatment.
5. Any illness that affects gastrointestinal absorption.
6. Ongoing or active systemic infection, active seropositive HIV, or known
active hepatitis B or C infection.
7. Any pre-existing condition or illness that, in the opinion of the
investigator or sponsor, would compromise patient safety or interfere with the
evaluation of the safety or efficacy of brigatinib.
8. Patients with rare hereditary problems of galactose intolerance, total
lactase deficiency or glucose-galactose malabsorption.
9. Patients with a history of cerebrovascular ischemia/hemorrhage with residual
deficits are not eligible (patients with a history of cerebrovascular
ischemia/hemorrhage remain eligible provided all neurologic deficits and
causative have resolved).
10. Uncontrolled seizure disorder (patients with seizure disorders that do not
require antiepileptic drugs, or are well controlled with stable doses of
antiepileptic drugs are eligible).
11. Patients with electrolytes imbalances >= grade 2 NCI CTCAE v5.0 are not
eligible (supplementation or medical intervention is allowed to correct
electrolyte imbalance before inclusion).
12. Patients with uncontrolled diabetes, i.e. patients with persistent
hyperglycemia >= grade 2 NCI CTCAE v5.0 despite well conducted treatment with
either oral anti glycemic agent and/or insulin are not eligible (patients with
well controlled diabetes with either insulin or oral anti glycemic agents are
eligible).
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 | CTIS2024-513412-10-00 |
| EudraCT | EUCTR2021-002713-34-NL |
| ClinicalTrials.gov | NCT04925609 |
| CCMO | NL78938.041.21 |