Part 1 (Dose escalation) of this study is a first-in-human (FIH), open-label, dose escalation safety and PK study of BNT142 in patients with advanced/metastatic CLDN6-positive solid tumors.
Part 2 (Expansion) will be a Phase IIa proof-of-concept study in up to three expansion cohorts of CLDN6 positive advanced/metastatic ovarian cancer, non-small cell lung cancer (NSCLC) of non-squamous type, and testicular cancer patients who have progressed on or after last prior treatment.
Key Inclusion Criteria:
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
For Part 1 and 2:
- 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 immunohistochemistry (IHC) assay in formalin-fixed paraffin-embedded
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.
- Measurable disease per RECIST 1.1 (measurable per RECIST 1.1 or evaluable per 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 the patient is not a candidate
for such available therapy, or patients with not otherwise specified (NOS) tumors (as
confirmed by histological diagnosis), rare tumors (defined as those occurring in <15
out of 100,000 people each year as per National Cancer Institute [NCI] guidelines) and
cancers of unknown primary, 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 from 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 standard of care therapy prior to enrollment.
Key Exclusion Criteria:
- Chemotherapy, or molecularly-targeted agents within 3 weeks or 5 half-lives (whichever
is longer) of the start of study treatment; immunotherapy/monoclonal antibodies within
3 weeks of the start of study treatment; nitrosoureas, antibody-drug conjugates, or
radioactive isotopes within 6 weeks of the start of study 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
non-target 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
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; and
- Are not undergoing acute corticosteroid therapy or steroid taper.
- Notes: Patients with central nervous system 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.
Lung
Other Female Genital
Other Male Genital
Ovary