This is an open-label, multicenter Phase I/IIa dose escalation, safety, pharmacokinetic (PK)
and pharmacodynamic (PD) trial of BNT151 with expansion cohorts in various solid tumor
indications. The trial consists of Part 1, Part 2A and Part 2B with adaptive design elements:
The monotherapy dose escalation (Part 1) of this clinical trial will enroll patients with
various solid tumors that are metastatic (Stage IV) or unresectable for whom there is no
available standard therapy likely to confer clinical benefit, or patients who are not
candidates for such available therapy. During combination dose escalation (Part 2A), patients
of different specific solid tumors (one cohort per indication) will be enrolled and treated
with a combination of BNT151 and the respective standard of care (SoC) treatment.
Part 2B is the expansion phase where a predefined number of patients in each indication
cohort will be treated with the confirmed recommended phase II dose (RP2D) of BNT151 in
combination with respective SoC.
- Histological documentation of the original primary tumor via a pathology report.
- Measurable disease per RECIST1.1.
For Part 1:
- Histologically confirmed solid tumor that is metastatic (Stage IV) or unresectable and
for whom there is no available standard therapy likely to confer clinical benefit, or
patient who is not a candidate for such available therapy. If there is no
contraindication, patients should have exhausted all SoC therapies before entering the
For all Parts:
- ≥18 years of age.
- Must sign an informed consent form (ICF) indicating that he or she understands the
purpose and procedures required for the trial and are willing to participate in the
trial prior to any trial-related assessments or procedures.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Adequate coagulation function at screening as required by the protocol.
- Adequate hematologic function at screening as required by the protocol.
- Adequate hepatic function at screening as required by the protocol.
- Adequate renal function at screening as required by the protocol.
- Able and willing to attend trial visits as required by the protocol.
- Women of childbearing potential (WOCBP) must have a negative serum (beta-human
chorionic gonadotropin [beta-hCG]) test/value at screening. Patients who are
postmenopausal or permanently sterilized can be considered as not having reproductive
- WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted
reproduction during the entire trial, until 6 months after last BNT151 treatment.
- A man who is sexually active with a woman of childbearing potential and has not had a
vasectomy must agree to use a barrier method of birth control, e.g. either condom with
spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm
or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men
must also not donate sperm during the trial and for 6 months after receiving the last
dose of BNT151.
- Use of any investigational medical product or device within 28 days before
administration of first dose of trial treatment.
- Has been receiving: radiotherapy, chemotherapy, or molecularly-targeted agents or
tyrosine kinase inhibitors within 2 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; any live vaccine within 4 weeks of the start of trial
treatment; nitrosoureas, antibody-drug conjugates, or radioactive isotopes within 6
weeks of the start of trial treatment.
- Ongoing participation in the active treatment phase of interventional clinical trial.
- Receives concurrent systemic (oral or IV) steroid therapy >10 mg prednisone daily or
its equivalent for an underlying condition.
- Has had major surgery within the 4 weeks before the first dose of BNT151.
- 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 BNT151.
- Has ongoing side effects to any prior therapy or procedures for any medical condition
not recovered to National Cancer Institute Common Terminology Criteria for Adverse
Events (NCI CTCAE) v5.0 Grade ≤1.
- 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 computed tomography (CT) or magnetic resonance
imaging (MRI) scan within 4 weeks before signing the informed consent;
- are not undergoing acute corticosteroid therapy or steroid taper.
- Has a history of a cerebrovascular accident or transient ischemic attack less than 6
- Effusions (pleural, pericardial, or ascites) requiring drainage.
- History of autoimmune disease active or past including but not limited to inflammatory
bowel disease, systemic lupus erythematosus (SLE), ankylosing spondylitis,
scleroderma, or multiple sclerosis. Has any active immunologic disorder requiring
immunosuppression with steroids or other immunosuppressive agents (e.g., azathioprine,
cyclosporine A) with the exception of patients with isolated vitiligo, resolved
childhood asthma or atopic dermatitis, controlled hypoadrenalism or hypopituitarism,
and patients with a history of Grave's disease with stable thyroid function. Patients
with controlled hyperthyroidism must be negative for thyroglobulin, thyroid peroxidase
antibodies, and thyroid stimulating immunoglobulin prior to administration of trial
- Known history of seropositivity for human immunodeficiency virus (HIV) with CD4+
T˗cell (CD4+) counts <350 cells/uL and with a history of acquired immunodeficiency
syndrome (AIDS)-defining opportunistic infections.
- Known history/positive serology for hepatitis B requiring active antiviral therapy
(unless immune due to vaccination or resolved natural infection or unless passive
immunization due to immunoglobulin therapy). Patients with positive serology must have
HBV viral load below the limit of quantification.
- Active HCV infection; patients who have completed curative antiviral treatment with
HCV viral load below the limit of quantification are allowed.
- Known hypersensitivity to a component of any trial treatment.
- Any contraindication to the combination therapies as per United States Prescribing
Information (USPI) or Summary of Product Characteristics (SmPC) for patients receiving
BNT151 in combination with other systemic anticancer agent(s).
- Another primary malignancy that has not been in remission for at least 2 years, with
the exception of those with a negligible risk of metastasis or death (including but
not limited to adequately treated carcinoma in situ of the cervix, basal or squamous
cell skin cancer, localized prostate cancer, or ductal carcinoma in situ).
- Abnormal ECGs that are clinically significant, such as Fridericia-corrected QT
prolongation >480 ms.
- In the opinion of the treating investigator, has any concurrent conditions that could
pose an undue medical hazard or interfere with the interpretation of the trial
results; these conditions include, but are not limited to:
- Ongoing or active infection requiring antibiotic/antiviral/antifungal therapy
- Concurrent congestive heart failure (New York Heart Association [NYHA] Functional
Classification Class III or IV)
- Concurrent unstable angina
- Concurrent cardiac arrhythmia requiring treatment (excluding asymptomatic atrial
- Acute coronary syndrome within the previous 6 months
- Pulmonary embolism within the previous 3 months
- Significant pulmonary disease (shortness of breath at rest or on mild exertion) for
example due concurrent severe obstructive pulmonary disease.
- Cognitive, psychological or psychosocial impediment that would impair the ability of
the patient to receive therapy according to the protocol or adversely affect the
ability of the patient to comply with the informed consent process, protocol, or
protocol-required visits and procedures.
- Is pregnant or breastfeeding.