To assess the safety and tolerability ofBNT141 at different dose levels.To identify the maximum tolerated dose (MTD) or maximally administered dose (MAD) /recommended Phase IIdose (RP2D) of BNT141 based on theoccurrence of dose-limiting toxicities(…
ID
Source
Brief title
Condition
- Soft tissue neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Occurrence of treatment-emergent adverse events
(TEAEs) within a patient including Grade >= 3, serious, fatal
TEAE by relationship.
Occurrence of dose reductions and discontinuation of
BNT141 due to TEAEs.
Occurrence of DLTs within a patient during the DLT
evaluation period
Secondary outcome
PK parameters including but not limited to area-under-theconcentration-
time curve (AUC), clearance (CL), volume of
distribution (Vd), maximum concentration (Cmax), time to
Cmax (tmax), measured concentration at the end of a dosing
interval [taken directly before next administration] (Ctrough),
and half-life (t*).
Objective response rate (ORR) is defined as the proportion
of patients in whom a complete response (CR) or partial
response ([PR], per RECIST 1.1) is confirmed as best
overall response.
Disease control rate (DCR) is defined as the proportion of
patients in whom a CR or PR or SD (per RECIST 1.1, SD
assessed at least 6 weeks after first dose) is observed as
best overall response.
• Duration of response (DOR) is defined as the time from
first objective response (CR or PR per RECIST 1.1) to first
occurrence of objective tumor progression (progressive
disease per RECIST 1.1) or death from any cause,
whichever occurs first.
Progression-free survival (PFS) is defined as the time from
first dose of BNT141 to first objective tumor progression
(progressive disease per RECIST 1.1), or death from any
cause, whichever occurs first.
• Overall survival (OS) is defined as the time from first dose
of BNT141 to death from any cause.
Correlation of CLDN18.2 expression level with clinical
outcomes.
Evaluation of PD biomarkers compared to baseline.
Anti-drug antibodies [ADAs] response.
Evaluate pre-treatment lipid status and potential
influence on BNT141 response.
Background summary
The study drug is a possible treatment for patients with solid tumors that are
called CLDN18.2. This type of tumor is expressed in various cancers and is
involved in the growth of cancer cells. The outcome of the assessment of the
CLDN18.2 status is used to select patients who might benefit from the treatment
with BNT141.
Study objective
To assess the safety and tolerability of
BNT141 at different dose levels.
To identify the maximum tolerated dose (MTD) or maximally administered dose
(MAD) /recommended Phase II
dose (RP2D) of BNT141 based on the
occurrence of dose-limiting toxicities
(DLTs) using the following definitions:
The MTD will be defined as the
highest tolerated dose, where less
than one-third of the patients
experience a DLT.
• The maximally administered dose
(MAD) is defined as the highest
dose administered, where all dose
levels were tolerated during dose
escalation.
• The RP2D will be defined based
on integrated evaluation of safety,tolerability, clinical benefit,
pharmacokinetic (PK), and PD
data, for all dose levels tested.
To characterize the PK profile of the
BNT141-encoded protein RiboMab01.
To evaluate the anti-tumor activity of
BNT141 according to Response
Evaluation Criteria in Solid Tumors
(RECIST) 1.1.
Exploratory objectives
To evaluate the efficacy of BNT141.
To assess Claudin 18.2 (CLDN18.2)
expression level as a potential
biomarker to predict clinical response
to BNT141.
To assess potential PD biomarkers of
BNT141.
To evaluate the immunogenicity of
BNT141.
To assess other exploratory markers
that may be collected in the trial to
better understand BNT141 treatment.
Study design
This trial is an open-label, multi-site, Phase I/Iia dose escalation, safety,
and PK trial of
BNT141 followed by expansion cohorts in patients with CLDN18.2-positive tumors.
CLDN18.2 positivity will be determined by a central laboratory during the
pre-screening
phase using a validated immunohistochemistry assay, and is defined as
moderate-tostrong
CLDN18.2 expression.
The trial design consists of three parts.
Please refert to section 4 of the protocol
Intervention
The trial design consists of three parts:
• Part 1A is a dose escalation of BNT141 as monotherapy in patients with
unresectable or metastatic CLDN18.2-positive solid tumors for which there is no
available standard therapy likely to confer clinical benefit, or the patient is
not a
candidate for such available therapy. Patients must have received all available
standard therapies and failed at least first-line standard of care (SOC)
therapy prior
to enrolment. The dose of BNT141 will be escalated until the MTD and/or RP2D of
BNT141 as monotherapy are defined. Eligible tumor types are gastric cancer,
gastroesophageal junction (GEJ) and esophageal adenocarcinoma, pancreatic,
biliary tract (cholangiocarcinoma and gallbladder cancer), and mucinous ovarian
cancers. Additionally, patients with specific tumors (including colorectal
cancer,
non-small-cell lung cancer, gastric subtype of endocervical adenocarcinoma)
where
there is scientific evidence that the CLDN18.2 could be elevated can be tested
for
CLDN18.2 expression.
• Part 1B is a dose escalation of BNT141 in combination with nab-paclitaxel and
gemcitabine in patients with advanced unresectable or metastatic CLDN18.2-
positive pancreatic adenocarcinoma or cholangiocarcinoma who are eligible for
treatment with nab-paclitaxel and gemcitabine. Part 1B intends to define the MTD
and/or RP2D of the combination.
• Part 2 (Expansion) consists of the following pre-defined expansion cohorts:
* CLDN18.2-positive unresectable locally advanced or metastatic pancreatic
adenocarcinoma eligible for treatment with nab-paclitaxel and gemcitabine.
* CLDN18.2-positive unresectable locally advanced or metastatic
cholangiocarcinoma eligible for treatment with nab-paclitaxel and gemcitabine.
Part 2 will be further defined via an amendment after careful evaluation of all
available
safety, PK and PD, and efficacy data generated in Parts 1A and 1B by the Safety
Review
Committee (SRC).
Study burden and risks
The trial is considered completed when all patients have had at least 12 months
survival
follow up or are lost to follow up or have withdrawn consent or have died or
the sponsor
discontinues the trial. However, the maximum trial duration is 3 years after
the last
subject*s first treatment in the trial.
Please refer to the schedule of events in the protocol for more information
An der Goldgrube 12
Mainz 55131
DE
An der Goldgrube 12
Mainz 55131
DE
Listed location countries
Age
Inclusion criteria
For all parts:
• Metastatic or unresectable solid tumor.
• Histological or cytological documentation of a solid tumor via a pathology
report.
CLDN18.2-positive tumor sample defined as moderate-to-strong CLDN18.2 protein
expression defined as intermediate (2+) to strong (3+) staining intensity in >=
50% of
tumor cells as assessed by central testing using a CLIA-validated
immunohistochemistry assay in formalin-fixed, paraffin-embedded (FFPE)
neoplastic tissues. New biopsies and archival bio-samples are allowed. Bone
biopsies are not allowed. Cytology specimens (including fine needle aspirates)
will
not be accepted for CLDN18.2 examination. If archival tissue samples from
several
points of time are available, the most recent one is preferred. Patients with a
lower
expression level or with CLDN18.2-negative cancers are not eligible.
Trial part-specific inclusion criteria:
• For Part 1A: Patients with solid tumors, for which there is no available
standard
therapy likely to confer clinical benefit, or the patient is not a candidate
for such
available therapy. Patients must have received all available standard therapies
and
failed at least first-line SOC therapy prior to enrolment. Measurable or
evaluable
disease per RECIST 1.1. Eligible tumor types are gastric cancer,
gastroesophageal
junction (GEJ) and esophageal adenocarcinoma, pancreatic, biliary tract
(cholangiocarcinoma and gallbladder cancer), and mucinous ovarian cancers.
Additionally, patients with specific tumors (including colorectal cancer,
non-smallcell
lung cancer, gastric subtype of endocervical adenocarcinoma) where there is
scientific evidence that the CLDN18.2 could be elevated can be tested for
CLDN18.2 expression.
• For Part 1B: Patients with advanced pancreatic adenocarcinoma or
cholangiocarcinoma who are eligible for treatment with nab-paclitaxel and
gemcitabine. Measurable or evaluable disease per RECIST 1.1.
• For Part 2 (Expansion):
* Cohort 1 - Pancreatic adenocarcinoma: pancreatic adenocarcinoma eligible
for treatment with nab-paclitaxel and gemcitabine. Measurable disease per
RECIST 1.1.
* Cohort 2 - Cholangiocarcinoma: cholangiocarcinoma eligible for treatment
with nab-paclitaxel and gemcitabine. Measurable disease per RECIST 1.1.
(Page 5 of the protocol)
Exclusion criteria
Patients who meet at least one of the following exclusion criteria will not be
eligible for trial
entry:
• Receiving: radiotherapy, chemotherapy, or molecularly-targeted agents within
3 weeks or 5 half-lives (whichever is longer) of the start of trial treatment;
immunotherapy/monoclonal antibodies within 3 weeks of the start of trial
treatment
(excluding BNT141); nitrosoureas, antibody-drug conjugates, or radioactive
isotopes within 6 weeks of the start of trial treatment. Palliative
radiotherapy will be
allowed.
• Receives concurrent systemic (oral or intravenous [IV]) steroid therapy
> 10 mg prednisone daily or its equivalent for an underlying condition.
Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is not considered a
form
of systemic treatment and is permitted.
• Major surgery within 4 weeks before the first dose of BNT141.
• Prior treatment with a CLDN18.2 targeting mAb other than BNT141.
• Ongoing or active infection requiring IV treatment with anti-infective
therapy that
has been administered less than 2 weeks prior to the first dose of BNT141.
• Side effects of any prior therapy or procedures for any medical condition not
recovered to National Cancer Institute Common Terminology Criteria for AEs
(NCICTCAE)
v.5 Grade <= 1, with the exception of anorexia, fatigue, hyperthyroidism,
hypothyroidism, and peripheral neuropathy, which must have recovered to
<= Grade 2. Alopecia of any grade is allowed.
• Current evidence of new or growing brain or leptomeningeal metastases during
screening. Patients with known brain or leptomeningeal metastases may be
eligible
if they have:
* Radiotherapy, surgery or stereotactic surgery for the brain or leptomeningeal
metastases.
* No neurological symptoms (excluding Grade <= 2 neuropathy).
* Stable brain or leptomeningeal disease on the computer tomography (CT) or
magnet resonance imaging (MRI) scan within 4 weeks before signing the
informed consent form (ICF).
* Not undergoing acute corticosteroid therapy or steroid taper.
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 |
|---|---|
| EudraCT | EUCTR2022-001843-25-NL |
| ClinicalTrials.gov | NCT04683939 |
| CCMO | NL83022.000.23 |