Clinical trial NCT05262530: Safety and Preliminary Efficacy Trial of BNT142 in Patients with CLDN6-positive Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Keywords: CLDN6-positive solid tumors
Lead sponsor: BioNTech SE
Sponsor class: INDUSTRY
First posted: 2022-03-02
Enrollment: 330
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is an open-label, multicenter, Phase I/IIa, dose escalation, safety, and pharmacokinetics (PK) study of BNT142 followed by expansion cohorts in patients with Claudin 6 (CLDN6)-positive advanced tumors.

Detailed description: 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.

Eligibility criteria: Key Inclusion Criteria:

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

For Part 1 and 2:

* Histological or cytological documentation of a malignant solid tumor (via a pathology report) that is metastatic or unresectable.
* CLDN6-positive tumor sample as assessed by central laboratory testing using a validated immunohistochemistry 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 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 guidelines) and cancers of unknown primary, not included in the pre-defined eligible tumor types (the last three upon approval by the medical monitor). Patients must have received all available standard therapies, including targeted therapies based on mutation status (per guidelines from the United States Food and Drug Administration \[FDA\], American Society of Clinical Oncology, European Society for Medical Oncology 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.

Primary outcomes:
measure: Occurrence of treatment emergent adverse events (TEAEs) including Grade ≥3, serious, or fatal TEAEs by causal relationship to study treatment
timeFrame: From first dose to 60 days after the last dose of BNT142
measure: Occurrence of dose reductions and discontinuation of BNT142 due to TEAEs
timeFrame: From first dose to 60 days after the last dose of BNT142
measure: Part 1: Occurrence of dose-limiting toxicities (DLTs) during the DLT evaluation period in the dose escalation
timeFrame: Assessed during the DLT period, i.e., up to 5 weeks after first dose of BNT142
measure: Part 2: Objective response rate (ORR)
timeFrame: Up to 36 months after last patient last dose
Secondary outcomes:
measure: Part 1: PK parameter: Area under the concentration-time curve in the dosing interval (AUC)
timeFrame: Pre-dose until 60 days after last dose
measure: Part 1: PK parameter: Clearance (CL)
timeFrame: Pre-dose until 60 days after last dose
measure: Part 1: PK parameter: Volume of distribution (Vd)
timeFrame: Pre-dose until 60 days after last dose
measure: Part 1: PK parameter: Maximum observed concentration (Cmax)
timeFrame: Pre-dose until 60 days after last dose
measure: Part 1: PK parameter: Time to maximum observed concentration (Tmax)
timeFrame: Pre-dose until 60 days after last dose
measure: Part 1: PK parameter: Concentration prior to next dose (Ctrough)
timeFrame: Pre-dose until 60 days after last dose
measure: Part 1: PK parameter: Minimum observed concentration (Cmin)
timeFrame: Pre-dose until 60 days after last dose
measure: Part 1: PK parameter: Elimination half-life (t½)
timeFrame: Pre-dose until 60 days after last dose
measure: Part 1: ORR
timeFrame: Up to 36 months after last patient last dose
measure: Disease control rate (DCR)
timeFrame: Up to 36 months after last patient last dose
measure: Duration of response (DOR)
timeFrame: Up to 36 months after last patient last dose
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics (START) - San Antonio
state: Texas
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
city: Singapore
country: Singapore
facility: National University Cancer Institute - National University Hospital
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore (recruiting only for Part 2)
city: Barcelona
country: Spain
facility: HM Nou Delfos General Hospital
city: Barcelona
country: Spain
facility: Hospital Universitario Vall D'Hebron
city: Madrid
country: Spain
facility: MD Anderson Cancer Center
city: Madrid
country: Spain
facility: START Madrid-FJD Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre - Centro de Actividades Ambulatorias
city: Madrid
country: Spain
facility: START Madrid CIOCC Hospital Universitario HM Sanchinarro
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria Campus Universitario de Teatinos
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
city: Liverpool
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust
city: London
country: United Kingdom
facility: Guy's Hospital - Guy's & St Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: Hammersmith Hospital, Imperial College School Of Medicine - Imperial College Healthcare NHS Trust
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute (Recruiting only for Part 2)
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust - Nottingham City Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital - Oxford University Hospitals NHS Foundation Trust
Study officials:
affiliation: BioNTech SE
name: BioNTech Responsible Person
role: STUDY_DIRECTOR
References: