Trial Title:
Safety and Preliminary Efficacy of BNT314 with or Without an Immune Checkpoint Inhibitor in Cancer Patients with Malignant Solid Tumors
NCT ID:
NCT06150183
Condition:
Advanced Malignant Solid Tumor
Conditions: Official terms:
Neoplasms
Pembrolizumab
Conditions: Keywords:
Immune Checkpoint Inhibitors
Pembrolizumab
Malignant solid tumors
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
BNT314
Description:
Intravenous infusion
Arm group label:
BNT314 + pembrolizumab
Arm group label:
BNT314 Monotherapy
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
Intravenous infusion
Arm group label:
BNT314 + pembrolizumab
Summary:
The purpose of this first-in-human study is to find out if BNT314 is safe when it is used
alone and when it is used together with another antibody cancer drug (pembrolizumab) in
patients with different types of cancer. Patients will receive either BNT314 alone or
BNT314 combined with pembrolizumab.
Phase 1 of the study consists of a dose escalation part, and a safety run-in (SRI) and
expansion part:
Dose escalation: In this part of the study, patients will be assigned to multiple dose
levels (DLs) of BNT314 given alone. By escalating the dose with a small group of
patients, the Maximum Tolerated Dose (MTD) which is the highest dose with acceptable
safety and manageable side effects, or the maximum administered dose (MAD) will be
investigated. At the end of this part, the Recommended Phase 2 Dose (RP2D) which is the
dose to be tested in Phase 2 will be decided.
Safety Run-In: In this part of the study, BNT314 will be combined with pembrolizumab.
Before starting the expansion part, the combination will be tested in another small group
of participants (12-28) to find out how safe this combination is.
Expansion: In this part of the study, BNT314 will be combined with pembrolizumab. After
the SRI is completed, the study will continue with the expansion part where up to 199
participants with different types of cancer will be included.
The Phase 2 part of the study will be introduced via an amendment to the study protocol.
Detailed description:
This is a multicenter, multinational safety study in patients with metastatic or advanced
malignant solid tumors for whom, at the discretion of the investigator, there is no
available standard therapy likely to confer clinical benefit, evaluating the safety,
tolerability, preliminary antitumor activity, pharmacokinetics (PK), pharmacodynamics
(PD), and immunogenicity of BNT314.
In the dose escalation part of the study, patients will periodically receive one infusion
of BNT314. In the combination therapy SRI and expansion part, BNT314 will be combined
with pembrolizumab and administered intravenously in periodic cycles to patients with
selected cancer indications.
Additional cohorts (backfill cohorts) administering BNT314 as monotherapy will assign
patients to specific DLs, based on the emerging safety, PK, and pharmacodynamic data.
This would allow for further assessment of dose- and exposure-response relationships for
clinical activity, safety, and tolerability to support BNT314 dose optimization.
The treatment period will last until progressive disease (PD), confirmed PD (as per
immune response evaluation criteria in solid tumors [iRECIST]), unacceptable toxicity, or
withdrawal of consent, whichever happens first.
For the combination therapy, the maximum treatment period will be 2 years. The maximum
study duration is 3 years after the last participant's first treatment in the study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Have the ability to voluntarily give informed consent by signing and dating the
informed consent form (ICF) before initiation of any study-specific procedures.
2. Are willing and able to comply with scheduled visits, treatment schedule, laboratory
tests, lifestyle restrictions, and other requirements of the study. This includes
that they are able to understand and follow study-related instructions.
3. Are ≥18 years of age at the time of giving informed consent.
4. Have measurable disease according to RECIST v1.1.
5. Have a life expectancy of >3 months.
6. Have Eastern Cooperative Oncology Group Performance Status score of 0 or 1 at
screening.
7. Have adequate coagulation function at screening as determined by:
- International normalized ratio or prothrombin time ≤1.5 × upper limit normal
(ULN; unless on therapeutic anticoagulants with values within therapeutic
window).
- Activated partial thromboplastin time ≤1.5 × ULN (unless on therapeutic
anticoagulants with values within therapeutic window).
8. Have adequate bone marrow/hematologic function at screening as determined by:
- Absolute neutrophil count (ANC) ≥1.5 × 10^9/L (≥1500/μL) (patients may not use
granulocyte colony stimulating factor or granulocyte-macrophage colony
stimulating factor to achieve these ANC levels in the past 7 days).
- Platelet count ≥100 × 10^9/L (≥100,000/μL).
- Hemoglobin ≥9 g/dL.
- Any blood transfusions ≤28 days before first dose of study treatment should be
documented.
9. Have adequate hepatic function at screening as determined by:
- Total bilirubin (Tbili) ≤1.5 × ULN OR direct bilirubin ≤ULN for patients with
Tbili levels >1.5 × ULN. Exception for patients in monotherapy: Patients with
Gilbert's syndrome must have a Tbili <3 mg/dL and direct bilirubin ≤ULN.
- Alanine aminotransferase and aspartate aminotransferase ≤2.5 ULN for patients
with or without liver metastases.
- Albumin ≥30 g/L.
10. Have adequate renal function at screening as determined by glomerular filtration
rate ≥45 mL/min/1.73 m^2 according to the abbreviated Modification of Diet in Renal
Disease equation.
11. Have adequate pancreas function at screening as determined by serum amylase and
lipase with no signs and symptoms of pancreatitis.
12. Patients of childbearing potential (POCBP) must have a negative urine and serum beta
human chorionic gonadotropin test at screening. Patients that are postmenopausal or
permanently sterilized (verified by medical records) will not be considered POCBP,
and therefore are not required to undergo pregnancy testing.
13. POCBP must agree to practice a highly effective form of contraception and to require
their male partners to use condoms with a spermicidal agent, starting at Visit D1
and thereafter until 120 days after receiving the last study treatment.
14. POCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted
reproduction during study, starting at Visit D1 and thereafter until 120 days after
receiving the last study treatment.
15. Males who are sexually active and have not had a bilateral vasectomy or orchidectomy
must agree to use condoms with a spermicidal agent and to require their female
partners to practice a highly effective form of contraception during the study,
starting at Visit D1 and thereafter until 120 days after receiving the last study
treatment.
16. Males must be willing to refrain from sperm donation, starting at Visit D1 and
thereafter until 120 days (one sperm cycle) after receiving the last study
treatment.
17. Patients must have a histologically confirmed advanced malignant solid tumor, having
experienced disease progression on or after standard therapy, or were intolerant of
or not eligible for standard therapy (only for the monotherapy dose escalation
part).
Inclusion criteria specific to selected tumor indications may apply only for the
combination therapy SRI and dose expansion parts of the study.
Exclusion Criteria:
1. Patients that have uncontrolled intercurrent illness, including but not limited to:
- Ongoing or active infection requiring treatment with anti-infective therapy
administered less than two weeks prior to first dose.
- Symptomatic congestive heart failure (Grade III or IV as classified by the New
York Heart Association), unstable angina pectoris, or symptomatic untreated
cardiac arrhythmia. Treated and/or asymptomatic cardiac arrythmia/atrial
fibrillation will be allowed.
- History of arterial thrombosis or pulmonary embolism within 6 months before the
first dose of study treatment.
- History of myocardial infarction within 6 months before the first dose of study
treatment.
- Uncontrolled hypertension defined as systolic blood pressure ≥160 mm Hg and/or
diastolic blood pressure ≥100 mm Hg, despite optimal medical management.
- Prolonged QTc interval at baseline of ≥470 milliseconds using Fridericia's QT
correction formula.
- Ongoing or recent (within one year of screening) evidence of significant
autoimmune disease that required treatment with systemic immunosuppressive
treatments, which may suggest risk for immune-related adverse events (irAEs).
- History of Grade 3 or higher irAEs that led to treatment discontinuation of a
checkpoint inhibitor. A patient with irAEs below Grade 3 that led to
discontinuation should be discussed with the sponsor. Grade 3 irAEs that have
fully recovered may also be discussed.
- History of chronic liver disease (e.g., alcoholic hepatitis or nonalcoholic
steatohepatitis, drug-related or autoimmune hepatitis) or evidence of hepatic
cirrhosis.
- History of non-treated intracerebral arteriovenous malformation (shunts),
non-treated cerebral aneurysm, spinal cord compression (from disease),
carcinomatous meningitis, or stroke will be excluded.
- History of acute or chronic pancreatitis of any etiology within 6 weeks prior
to the start of study treatment.
- Evidence of interstitial lung disease.
- Ongoing pneumonitis or history of noninfectious pneumonitis that has required
steroids.
- Transient ischemic attack less than one month prior to screening will be
excluded.
- History of brain/central nervous system (CNS) metastases. Patients with newly
identified or known unstable or symptomatic CNS metastases will be excluded.
Patients with previously treated brain metastases are allowed provided lesions
are radiologically stable (i.e., without evidence of progression) for at least
28 days by repeat imaging, latest imaging performed maximum 6 weeks prior to
Cycle 1, Day 1.
- Serious, non-healing wound, skin ulcer (of any grade), or bone fracture will be
excluded.
- Other concurrent severe and/or uncontrolled medical condition that would, in
the investigator's judgment, contraindicate patient participation in this
clinical study (e.g., acute or chronic pancreatitis, active hepatitis). Known
primary immunodeficiencies, either cellular (e.g., DiGeorge syndrome, T-cell
negative severe combined immunodeficiency [SCID] or combined T- and B-cell
immunodeficiencies (e.g., T- and B-cell negative SCID, Wiskott Aldrich
syndrome, ataxia telangiectasia, common variable immunodeficiency).
- Major surgery within 3 weeks before signature of the ICF unless fully recovered
from the surgery in the opinion of the investigator.
2. Prior therapy:
- Radiotherapy within 14 days prior to first BNT314 administration. Palliative
radiotherapy will be allowed, but not to target lesions.
- Any epithelial cell adhesion molecule- or 4-1BB-targeting treatment.
- Treatment with an anticancer agent within 4 weeks or for systemic therapies
after at least five half-lives of the drug, whichever is shorter, prior to
study treatment administration.
- Patient has received any investigational agent (including investigational
vaccines) or used an invasive investigational medical device within 28 days
before the planned first dose of BNT314 or is currently enrolled in an
interventional study. Patients who are in the follow-up phase of an
interventional study may participate if they have not received an
investigational agent within 28 days (or five half-lives, whichever is longer)
of the first dose of BNT314.
- Patient has a condition requiring systemic treatment with either
corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive
medications within 14 days of the first dose of BNT314. Inhaled or topical
steroids, and adrenal or pituitary replacement steroid >10 mg daily prednisone
equivalent, are permitted in the absence of active autoimmune disease.
- Patient has received granulocyte or granulocyte/macrophage colony stimulating
factor (G-CSF/GM-CSF) support within 2 weeks prior to first BNT314
administration or is chronically transfusion dependent; G-CSF and other
hematopoietic factors may be used in the management of acute toxicity (such as
febrile neutropenia) or prophylactically, when clinically indicated at the
investigator's discretion.
- Received any live vaccine within 30 days prior to the start of study treatment.
3. Any positive test for hepatitis B (defined as positive for hepatitis B surface
antigen or hepatitis B virus DNA), indicating acute or chronic infection.
4. Any positive test for hepatitis C (defined as positive for hepatitis C virus
antibody or hepatitis C virus RNA), indicating acute or chronic infection.
5. Known alcohol dependency within 6 months enrollment in this study.
6. Planned enrollment in another study of an IMP, starting after Visit D1 and
continuously until the last planned visit in this study.
7. Have a medical, psychological, or social condition which, in the opinion of the
investigator, could compromise their wellbeing if they participate in the study, or
that could prevent, limit, or confound the protocol specified assessments or
procedures, or that could impact adherence to protocol-described requirements.
8. Are subject to exclusion periods from another investigational study.
9. Are vulnerable individuals as per International Council for Harmonisation E6
definition, i.e., are individuals whose willingness to participate in a clinical
study may be unduly influenced by the expectation, whether justified or not, of
benefits associated with participation, or of a retaliatory response from senior
members of a hierarchy in case of refusal to participate.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
START Midwest
Address:
City:
Grand Rapids
Zip:
49546
Country:
United States
Status:
Recruiting
Facility:
Name:
Carolina BioOncology Institute, LLC
Address:
City:
Huntersville
Zip:
28078
Country:
United States
Status:
Recruiting
Facility:
Name:
Cleveland Clinic
Address:
City:
Cleveland
Zip:
44195
Country:
United States
Status:
Recruiting
Facility:
Name:
GZA Ziekenhuizen
Address:
City:
Antwerpen
Zip:
2018
Country:
Belgium
Status:
Recruiting
Facility:
Name:
CHU de Liège
Address:
City:
Liege
Zip:
4000
Country:
Belgium
Status:
Recruiting
Facility:
Name:
Clinica Universidad de Navarra
Address:
City:
Pamplona
Zip:
31008
Country:
Spain
Status:
Recruiting
Facility:
Name:
Royal Marsden Hospital - London
Address:
City:
London
Zip:
SW36JJ
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
The Christie Hospital
Address:
City:
Manchester
Zip:
M20 4BX
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
Northern Centre for Cancer Care
Address:
City:
Newcastle
Zip:
NE7 7DN
Country:
United Kingdom
Status:
Recruiting
Start date:
November 30, 2023
Completion date:
July 2027
Lead sponsor:
Agency:
BioNTech SE
Agency class:
Industry
Collaborator:
Agency:
Genmab
Agency class:
Industry
Source:
BioNTech SE
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06150183
