First-in-human, open-label, multicenter, Phase I/IIa, dose escalation trial with expansion cohorts to evaluate safety and preliminary efficacy of BNT142 in patients with CLDN6-positive advanced solid tumors

Phase 2

• Conditions: cancer; tumors; 10027655

• Registration Number: NL-OMON53910
• Lead Sponsor: BioNTech SE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 24 June 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 14

Inclusion Criteria

For both parts:
• Histological or cytological documentation of a solid tumor that is metastatic
or unresectable via a pathology report.
• CLDN6-positive tumor sample as assessed by central laboratory testing using a
validated IHC assay (CLAUDENTIFY®6 IHC-Assay) in formalin-fixed
paraffin-embedded (FFPE) neoplastic tissues or alternatively from fresh tissue
if archival tissue is unavailable. If archival tissue samples from several
points of time are available, the most recent one is preferred.

The CLAUDENTIFY®6 IHC-Assay test is intended for use as a semi-quantitative
immunohistochemistry assay for specific detection of CLDN6 protein expression
in FFPE neoplastic tissues. The test results of scored tumor staining intensity
and percentage of stained tumor cells present, will be used as a pre-screening
test to identify patients with CLDN6-expressing positive tumors.

• Measurable disease per RECIST 1.1 (measurable per RECIST 1.1 or evaluable per
Gynecologic Cancer Intergroup [GCIG] criteria for ovarian tumors).

For Part 1 (Dose escalation):
• Patients with advanced/metastatic ovarian (including fallopian tube and
peritoneal), non-squamous NSCLC, endometrial, or testicular cancer, for whom
there is no available standard therapy likely to confer clinical benefit, or
patients with NOS tumors (as confirmed by histological diagnosis), rare tumors
(defined as those occurring in <15 out of 100,000 people each year as per NCI
guidelines) and CUP, not included in the pre-defined eligible tumor types.
Patients must have received all available standard therapies, including
targeted therapies based on mutation status (per guidelines form the US Food
and Drug Administration [FDA], American Society of Clinical Oncology [ASCO],
European Society for Medical Oncology [ESMO] or local guidelines used at the
site), and failed at least first line SOC therapy prior to enrollment.

For Part 2 (Expansion):
• Expansion Cohort 1: CLDN6-positive ovarian (including fallopian tube and
peritoneal) cancer patients who have received at least one systemic treatment
regimen for advanced/metastatic disease with radiographic disease progression
on or after last prior treatment and who are not eligible for SOC therapy at
the discretion of the investigator.
• Expansion Cohort 2: CLDN6-positive non-squamous NSCLC who have received at
least one prior systemic treatment regimen for advanced/metastatic disease with
radiographic disease progression on or after last prior treatment and who are
not eligible for SOC therapy at the discretion of the investigator.
• Expansion Cohort 3: CLDN6-positive testicular cancer patients who have
received at least one systemic treatment regimen for advanced/metastatic
disease with radiographic disease progression on or after last prior treatment
and who are not eligible for SOC therapy at the discretion of the investigator.
Note: Patients are considered as not eligible for SOC therapy if in the opinion
of the investigator, e.g., there is no effective SOC therapy available, SOC is
contraindicated or patient has refused SOC treatment.

Exclusion Criteria

Patients who meet any of the following exclusion criteria will not be eligible
for trial entry:
• 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; nitrosoureas,
antibody-drug conjugates, or radioactive isotopes within 6 weeks of the start
of trial treatment.
• Radiotherapy in the last 6 weeks prior to the first dose of BNT142 (excluding
brain radiotherapy for which 3 weeks prior to the first dose of BNT142 is
allowed). Previously irradiated tumor lesions cannot be considered as target
lesions or nontarget lesions in this study.
• Concurrent systemic (oral or intravenous [IV]) steroid therapy >10 mg
prednisone daily or its equivalent for an underlying condition apart from
physiologic corticosteroid replacement therapy.
• Major surgery within 4 weeks before the first dose of BNT142.
• 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
BNT142.
• Prior treatment with a CLDN6 targeting therapy.
• Side effects of any prior therapy or procedures for any medical condition not
recovered to National Cancer Institute Common Terminology Criteria for Adverse
Events (NCI-CTCAE) v.5 Grade <=1, except for 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 metastases may be eligible if they:
* Had radiotherapy, surgery or stereotactic surgery for the brain metastases;
* Have no neurological symptoms (excluding Grade <=2 neuropathy);
* Have stable brain metastasis on the computer tomography (CT) or magnetic
resonance imaging (MRI) scan within 4 weeks before signing the informed consent
form (ICF); and
* Are not undergoing acute corticosteroid therapy or steroid taper. Notes:
Patients with central nervous system (CNS) symptoms should undergo a CT scan or
MRI of the brain to exclude new or progressive brain metastases. Spinal bone
metastases are allowed, unless imminent fracture with cord compression is
anticipated.
• Pregnant or breastfeeding or planning to get pregnant within 6 months of the
last dose of BNT142.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>___________________<br /><br>PRIMARY ENDPOINTS<br /><br><br /><br>• Occurrence of TEAEs including Grade >=3, serious, or fatal TEAEs by causal<br /><br>relationship to trial treatment.<br /><br>• Occurrence of dose reductions and discontinuation of BNT142 due to TEAEs.<br /><br><br /><br>• Occurrence of DLTs during the DLT evaluation period (Cycle 1, i.e., 21 days<br /><br>after the first dose) during the dose escalation.<br /><br><br /><br>• ORR is defined as the proportion of patients in whom a confirmed CR or PR,<br /><br>per RECIST 1.1, and per GCIG criteria incorporating RECIST 1.1 and CA 125 for<br /><br>the ovarian cancer population is the best overall response.</p><br>