Phase I/IIa, first-in-human, open-label, dose escalation trial with expansion cohorts to evaluate safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of BNT141 as a monotherapy and in combination with other anti-cancer agents in patients with CLDN18.2-positive solid tumors
- Conditions
- CLDN18.2-positive solid tumors / malignant tumor10072990
- Registration Number
- NL-OMON53640
- Lead Sponsor
- BioNTech SE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 58
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)
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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Occurrence of treatment-emergent adverse events<br /><br>(TEAEs) within a patient including Grade >= 3, serious, fatal<br /><br>TEAE by relationship.<br /><br>Occurrence of dose reductions and discontinuation of<br /><br>BNT141 due to TEAEs.<br /><br>Occurrence of DLTs within a patient during the DLT<br /><br>evaluation period</p><br>
- Secondary Outcome Measures
Name Time Method