Extensive-stage Small Cell Lung Cancer, Solid Tumor
Conditions
Keywords
Solid Tumor, Extensive-stage Small Cell Lung Cancer
Brief summary
This first-in-human (FIH) trial aimed to establish a safe dose of BNT411 as a monotherapy and in combination with atezolizumab, carboplatin and etoposide. BNT411 is a toll-like receptor 7 (TLR7) agonist which is expected to mount broad innate and adaptive immune reactions, especially in combination with cytotoxic therapies and immune checkpoint inhibitors.
Detailed description
The first part (Part 1A) of this trial was a FIH, open-label, dose-escalation trial studying BNT411 monotherapy in patients with different types of malignant solid tumors in order to determine the safety profile of BNT411. The second part (Part 1B) aimed to determine further the safety profile of BNT411 in combination with atezolizumab, carboplatin and etoposide in patients with chemotherapy-naïve ES-SCLC. The third part (Part 2) was the expansion phase to explore BNT411 further as a monotherapy or in combination with atezolizumab, carboplatin and etoposide in select tumor indications. Different treatment schedules and other indications were planned to be explored in Part 2 of this trial, however, the sponsor decided not to continue with this part of this trial.
Interventions
DRUGBNT411
intravenous
DRUGAtezolizumab
intravenous
DRUGCarboplatin
intravenous
DRUGEtoposide
intravenous
Sponsors
BioNTech SE
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For Part 1A: * Histologically confirmed solid tumor (cytology was allowed for non-small cell lung cancer \[NSCLC\], small cell lung cancer \[SCLC\] and pancreatic cancer) that was metastatic or unresectable and for which there was no available standard therapy likely to confer clinical benefit, or patients who were not candidates for such available therapy. For Part 1B: * Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group \[VALG\] staging system) who received no prior chemotherapy for extensive stage disease. * Those treated with prior chemo/radiotherapy with curative intent for limited-stage small cell lung cancer (LS-SCLC) were treatment-free for at least 6 months since last chemo/radiotherapy. * Did not have interstitial lung disease or active, non-infectious pneumonitis. For Both Part 1A and Part 1B: * Male and female \>= 18 years of age. * Must have signed an informed consent form (ICF) indicating that he or she understood the purpose of and procedures required for the trial and were 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. * Measurable disease according to RECIST 1.1. * Albumin level at screening \>= 30 g/L. * Adequate coagulation function at screening as determined by: 1. International normalized ratio (INR) or prothrombin time \<= 1.5 x upper limit normal (ULN; unless on therapeutic anticoagulants with values within therapeutic window), 2. Activated partial thromboplastin time (aPTT) \<= 1.5 x ULN (unless on therapeutic anticoagulants with values within therapeutic window). * Adequate hematologic function at screening as determined by: 1. White blood cell count (WBC) \>= 3 x 10\^9/L, 2. Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (patient could not use granulocyte-colony stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF) to achieve these WBC and ANC levels), 3. Platelet count \>= 100 x 10\^9/L, 4. Hemoglobin (Hgb) \>= 9.0 g/dL. * Adequate hepatic function at screening as determined by: 1. Total bilirubin \<= 1.5 mg/dL (or \<= 2.0 mg/dL for patients with known Gilbert's syndrome), 2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<= 2.5 x ULN; or \<= 5 x ULN in patients with metastatic liver disease. * Adequate renal function at screening as determined by: a. Glomerular filtration rate (GFR) \>= 60 mL/min/1.73 m\^2 - e.g., according to the abbreviated Modification of Diet in Renal Disease (MDRD) equation: GFR = 186 × (SCr\^-1.154) × (age\^-0.203) (where SCr, the serum creatinine level, was expressed in mg/dL; multiplied by 0.742 if the patient was female; multiplied by 1.212, if the patient was African-American (Levey et al., 1999). * Were able to attend trial visits as required by the protocol. * Women of childbearing potential (WOCBP) must have had a negative serum (beta-human chorionic gonadotropin \[beta-hCG\]) test/value at screening. Patients who were postmenopausal or permanently sterilized were considered as not having reproductive potential. * WOCBP must have agreed not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the entire trial, until 6 months after last BNT411 treatment. * A man who was sexually active with a WOCBP and had not had a vasectomy must have agreed 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 BNT411. * All patients must have provided a Formalin Fixed Paraffin Embedded (FFPE) sample from the latest available archival tumor tissue. If such tissue was not provided, the sponsor's approval of enrollment was needed.
Exclusion criteria
Prior and Concomitant Therapy: * Had received prior systemic therapy with a TLR7 agonist. * Had been receiving: radiotherapy, chemotherapy, or molecularly-targeted agents or tyrosine kinase inhibitors within 2 weeks or 5 half-lives (whichever was 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. * Received concurrent systemic (oral or intravenous) steroid therapy \>10 mg prednisone daily or its equivalent for an underlying condition. * Received concurrent strong inhibitors or inducers of the cytochrome P450 enzymes. * Had major surgery within the 4 weeks before the first dose of BNT411. * Had ongoing or active infection requiring intravenous treatment with anti-infective therapy that has been administered less than two weeks prior to first dose of trial treatment. * Had 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. * Notes: peripheral neuropathy Grade \<= 2 was allowed; alopecia of any grade was allowed. Medical Conditions * Evidence of new or growing brain or leptomeningeal metastases during screening. Patients with known brain or leptomeningeal metastases might have been eligible if they: 1. had radiotherapy, surgery or stereotactic surgery for the brain or leptomeningeal metastases, 2. have no neurological symptoms (excluding Grade ≤2 neuropathy), 3. have stable brain or leptomeningeal disease on the computed tomography (CT) or magnetic resonance imaging (MRI) scan within 4 weeks before signing the informed consent, 4. were not undergoing acute corticosteroid therapy or steroid taper. * Notes: Patients with central nervous system symptoms had to undergo a CT scan or MRI of the brain to exclude new or progressive brain metastases. Spinal bone metastases were allowed, unless imminent fracture with cord compression was anticipated. * Had history of seizures other than isolated febrile seizure in childhood; had a history of a cerebrovascular accident or transient ischemic attack less than 6 months ago. * Had effusions (pleural, pericardial, or ascites) requiring drainage. * Had eye pathology likely to confound observation of potential ocular adverse events. * Had a fever \>=38°C within 3 days before signing the ICF. * Had a 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. Had 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 euthyroid patients with a history of Grave's disease. Patients with controlled hyperthyroidism must have been negative for thyroglobulin, thyroid peroxidase antibodies, and thyroid-stimulating immunoglobulin prior to trial drug administration. * Had known history of seropositivity for human immunodeficiency virus (HIV) with CD4+ T-cell (CD4+) counts \<350 cells/µL and with a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections. * Had known history/positive serology for hepatitis B requiring active anti-viral therapy (unless immune due to vaccination or resolved natural infection or unless passive immunization due to immunoglobulin therapy). Patients with positive serology must have had Hepatitis B virus (HBV) viral load below the limit of quantification. * Active Hepatitis C virus (HCV) infection; patients who had completed curative antiviral treatment with HCV viral load below the limit of quantification were allowed. * Notes: Country-specific criteria for Germany - To confirm that a patient would be eligible, an active infection with HIV/Hepatitis B or C was ruled out by serum blood test at screening. * Had a known hypersensitivity to a component of BNT411 drug product, or another similar compound. * Had 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 (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, or ductal carcinoma in situ). Other Comorbidities * Had abnormal electrocardiograms (ECGs) that were clinically significant, such as Framingham-corrected QT interval \>480 ms. * In the opinion of the treating investigator, had any concurrent conditions that could pose an undue medical hazard or interfere with the interpretation of the trial results; these conditions included, but were not limited to: 1. ongoing or active infection requiring antibiotic/antiviral/antifungal therapy, 2. concurrent congestive heart failure (New York Heart Association \[NYHA\] Functional Classification Class III or IV), 3. concurrent unstable angina, 4. concurrent cardiac arrhythmia requiring treatment (excluding asymptomatic atrial fibrillation), 5. acute coronary syndrome within the previous 6 months, 6. significant pulmonary disease (shortness of breath at rest or on mild exertion) for example due concurrent severe obstructive pulmonary disease. * Had a 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. * Was pregnant or breastfeeding. * Had any contraindication to atezolizumab, carboplatin or etoposide as per US prescribing information (USPI) or summary of product characteristics (SmPC) in Part 1B.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | Cycle 1 (21 Days) | DLTs were defined as any non-immune-related adverse events (AEs) or immune-related AEs during the first treatment cycle that was of Grade 3 and that did not resolve to Grade 1 or lower within a week, or that were of Grade 4. AEs were graded for severity using National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE v5.0), where Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4 - Life-threatening consequences; and Grade 5: Death related to AE. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | From Baseline until 60 days after last dose of study treatment (3 years and 11 months) | A TEAE was defined as any AE with an onset date on or after the first administration of trial treatment (if AE was absent before the first administration of trial treatment) or worsened after the first administration of trial treatment (if AE was present before the first administration of trial treatment). AEs occurring more than 60 days after last treatment administration were considered as treatment-emergent only if assessed as related to the trial treatment by the investigator. Serious adverse event (SAE): any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect or was another medically important condition. AE were graded for severity using NCI-CTCAE v5.0, where Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4 - Life-threatening consequences; and Grade 5: Death related to AE. |
| Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs | From Baseline until 60 days after last dose of study treatment (3 years and 11 months) | Participants with dose reduction and/or discontinuation of BNT411 due to TEAEs are reported. |
| Maximal Tolerated Dose (MTD) of BNT411 | Cycle 1 (21 days) | The MTD defined as the highest tolerated dose was reported based on the DLTs and TEAEs experienced by participants. |
| Recommended Phase 2 Dose (RP2D) of BNT411 | Cycle 1 (21 days) | RP2D was based on integrated evaluation of safety, tolerability, clinical benefit, pharmacokinetic (PK), and pharmacodynamic data, for all dose levels was tested. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK Assessment for BNT411: Trough Concentration (Ctrough) | Part 1A: Start of infusion on Cycle 1 Day 8, Day 15, Day 22, Day 43; Day 85; Part 1B: Start of infusion on Cycle 1 Day 8, Day 15, Day 23, Day 44 (each cycle duration=21 days) | Ctrough defined as the pre-dose concentrations of BNT411 was estimated from the plasma concentrations of BNT411. |
| Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last) | Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days) | AUC0-last defined as the AUC from time 0 to the last measurable time-point was calculated from plasma concentrations of BNT411 using the linear-log trapezoidal method. |
| PK Assessment for BNT411: Terminal Elimination Half-life (T1/2) | Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days) | Terminal elimination half-life was estimated from the plasma concentrations of BNT411. |
| PK Assessment for BNT411: Clearance (CL) | Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days) | Clearance reflects the elimination of the drug from the body was estimated from plasma concentrations of BNT411 as Dose/AUC0-inf. Dose was converted, as necessary, to reflect the amount of anhydrous BNT411 administered. |
| PK Assessment for BNT411: Volume of Distribution (Vd) | Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days) | Volume of distribution (Vd) is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vd was estimated from plasma concentrations of BNT411. |
| PK Assessment for BNT411: Maximum Plasma Concentration (Cmax) | Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days) | Cmax defined as the maximum observed plasma concentration was estimated from plasma concentrations of BNT411. |
| PK Assessment for BNT411: Time to Reach Cmax (Tmax) | Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days) | Tmax defined as the time to reach maximum (peak) concentration was estimated from plasma concentrations of BNT411. |
Countries
Germany, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
The trial was planned with three parts: Part 1A, Part 1B, and Part 2. Part 2, which was planned to consist of expansion cohorts in solid tumors was not conducted as the trial was terminated prematurely.
Participants by arm
| Arm | Count |
|---|---|
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg Participants received BNT411 at a starting dose of 0.05 mcg/kg as an IV infusion once a week in a 3-week cycle for the first 4 cycles (on Days 1, 8, and 15; each cycle duration=21 days) followed by once every 3 weeks (on Day 1) from Cycle 5 onwards until progressive disease, unacceptable AEs, withdrawal of consent, lost to follow-up or death whichever occurs first. | 2 |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg Participants received BNT411 at a dose of 0.15 mcg/kg as an IV infusion once a week in a 3-week cycle for the first 4 cycles (on Days 1, 8, and 15; each cycle duration=21 days) followed by once every 3 weeks (on Day 1) from Cycle 5 onwards until progressive disease, unacceptable AE, withdrawal of consent, lost to follow-up or death whichever occurs first. | 1 |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg Participants received BNT411 at a dose of 0.45 mcg/kg as an IV infusion once a week in a 3-week cycle for the first 4 cycles (on Days 1, 8, and 15; each cycle duration=21 days) followed by once every 3 weeks (on Day 1) from Cycle 5 onwards until progressive disease, unacceptable AE, withdrawal of consent, lost to follow-up or death whichever occurs first. | 1 |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg Participants received BNT411 at a dose of 1.2 mcg/kg as an IV infusion once a week in a 3-week cycle for the first 4 cycles (on Days 1, 8, and 15; each cycle duration=21 days) followed by once every 3 weeks (on Day 1) from Cycle 5 onwards until progressive disease, unacceptable AE, withdrawal of consent, lost to follow-up or death whichever occurs first. | 3 |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg Participants received BNT411 at a dose of 2.4 mcg/kg as an IV infusion once a week in a 3-week cycle for the first 4 cycles (on Days 1, 8, and 15; each cycle duration=21 days) followed by once every 3 weeks (on Day 1) from Cycle 5 onwards until progressive disease, unacceptable AE, withdrawal of consent, lost to follow-up or death whichever occurs first. | 4 |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg Participants received BNT411 at a dose of 4.8 mcg/kg as an IV infusion once a week in a 3-week cycle for the first 4 cycles (on Days 1, 8, and 15; each cycle duration=21 days) followed by once every 3 weeks (on Day 1) from Cycle 5 onwards until progressive disease, unacceptable AE, withdrawal of consent, lost to follow-up or death whichever occurs first. | 14 |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg Participants received BNT411 at a dose of 6.0 mcg/kg as an IV infusion once a week in a 3-week cycle for the first 4 cycles (on Days 1, 8, and 15; each cycle duration=21 days) followed by once every 3 weeks (on Day 1) from Cycle 5 onwards until progressive disease, unacceptable AE, withdrawal of consent, lost to follow-up or death whichever occurs first. | 8 |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg Participants received BNT411 at a dose of 7.2 mcg/kg as an IV infusion once a week in a 3-week cycle for the first 4 cycles (on Days 1, 8, and 15; each cycle duration=21 days) followed by once every 3 weeks (on Day 1) from Cycle 5 onwards until progressive disease, unacceptable AE, withdrawal of consent, lost to follow-up or death whichever occurs first. | 6 |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg Participants received BNT411 at a dose of 9.6 mcg/kg as an IV infusion once a week in a 3-week cycle for the first 4 cycles (on Days 1, 8, and 15; each cycle duration=21 days) followed by once every 3 weeks (on Day 1) from Cycle 5 onwards until progressive disease, unacceptable AE, withdrawal of consent, lost to follow-up or death whichever occurs first. | 6 |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg Participants received BNT411 at a dose of 1.2 mcg/kg as an IV infusion in combination with atezolizumab, carboplatin and etoposide once a week in a 3-week cycle for the first 4 cycles (on Days 2, 8, and 15; each cycle duration=21 days) followed by once every 3 weeks (on Day 2) from Cycle 5 onwards until progressive disease, unacceptable AE, withdrawal of consent, lost to follow-up or death whichever occurs first. | 3 |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg Participants received BNT411 at a dose of 2.4 mcg/kg as an IV infusion in combination with atezolizumab, carboplatin and etoposide once a week in a 3-week cycle for the first 4 cycles (on Days 2, 8, and 15; each cycle duration=21 days) followed by once every 3 weeks (on Day 2) from Cycle 5 onwards until progressive disease, unacceptable AE, withdrawal of consent, lost to follow-up or death whichever occurs first. | 4 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 1 | 1 | 1 | 2 | 4 | 11 | 4 | 4 | 5 | 2 | 3 |
| Overall Study | Enrolled but not treated | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 0 | 0 | 0 |
| Overall Study | Trial closure | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 3 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 11 Participants | 6 Participants | 5 Participants | 4 Participants | 1 Participants | 3 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 4 Participants | 14 Participants | 8 Participants | 5 Participants | 5 Participants | 3 Participants | 4 Participants | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Reportable | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 11 Participants | 8 Participants | 5 Participants | 5 Participants | 3 Participants | 4 Participants | 45 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 6 Participants | 3 Participants | 2 Participants | 5 Participants | 1 Participants | 3 Participants | 24 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants | 3 Participants | 2 Participants | 8 Participants | 5 Participants | 4 Participants | 1 Participants | 2 Participants | 1 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 2 | 1 / 1 | 1 / 1 | 2 / 3 | 4 / 4 | 11 / 15 | 4 / 9 | 4 / 6 | 5 / 6 | 2 / 3 | 3 / 4 |
| other Total, other adverse events | 2 / 2 | 1 / 1 | 1 / 1 | 3 / 3 | 4 / 4 | 14 / 14 | 8 / 8 | 6 / 6 | 6 / 6 | 3 / 3 | 4 / 4 |
| serious Total, serious adverse events | 1 / 2 | 0 / 1 | 1 / 1 | 1 / 3 | 1 / 4 | 5 / 14 | 3 / 8 | 4 / 6 | 4 / 6 | 2 / 3 | 3 / 4 |
Outcome results
Primary
Maximal Tolerated Dose (MTD) of BNT411
The MTD defined as the highest tolerated dose was reported based on the DLTs and TEAEs experienced by participants.
Time frame: Cycle 1 (21 days)
Population: Analysis was performed on DLT evaluable set. Data for this outcome measure was planned to be analyzed and reported for all participants collectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | Maximal Tolerated Dose (MTD) of BNT411 | 6.0 microgram/kilogram (mcg/kg) |
Primary
Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs
Participants with dose reduction and/or discontinuation of BNT411 due to TEAEs are reported.
Time frame: From Baseline until 60 days after last dose of study treatment (3 years and 11 months)
Population: Analysis was performed on safety set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs | Dose Reduction of BNT411 | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs | Discontinuation of BNT411 due to TEAEs | 1 Participants |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs | Dose Reduction of BNT411 | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs | Discontinuation of BNT411 due to TEAEs | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs | Dose Reduction of BNT411 | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs | Discontinuation of BNT411 due to TEAEs | 1 Participants |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs | Dose Reduction of BNT411 | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs | Discontinuation of BNT411 due to TEAEs | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs | Dose Reduction of BNT411 | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs | Discontinuation of BNT411 due to TEAEs | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs | Discontinuation of BNT411 due to TEAEs | 1 Participants |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs | Dose Reduction of BNT411 | 1 Participants |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs | Discontinuation of BNT411 due to TEAEs | 1 Participants |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs | Dose Reduction of BNT411 | 1 Participants |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs | Dose Reduction of BNT411 | 3 Participants |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs | Discontinuation of BNT411 due to TEAEs | 1 Participants |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs | Dose Reduction of BNT411 | 3 Participants |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs | Discontinuation of BNT411 due to TEAEs | 0 Participants |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs | Dose Reduction of BNT411 | 0 Participants |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs | Discontinuation of BNT411 due to TEAEs | 1 Participants |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs | Dose Reduction of BNT411 | 0 Participants |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs | Discontinuation of BNT411 due to TEAEs | 3 Participants |
Primary
Number of Participants With Dose Limiting Toxicities (DLTs)
DLTs were defined as any non-immune-related adverse events (AEs) or immune-related AEs during the first treatment cycle that was of Grade 3 and that did not resolve to Grade 1 or lower within a week, or that were of Grade 4. AEs were graded for severity using National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE v5.0), where Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4 - Life-threatening consequences; and Grade 5: Death related to AE.
Time frame: Cycle 1 (21 Days)
Population: Analysis was performed on DLT evaluable set that included participants who received at least one dose of BNT411 and have completed the DLT evaluation period and meet the minimum exposure criterion or have experienced a DLT during the DLT evaluation period (Cycle 1).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 2 Participants |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 2 Participants |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs
A TEAE was defined as any AE with an onset date on or after the first administration of trial treatment (if AE was absent before the first administration of trial treatment) or worsened after the first administration of trial treatment (if AE was present before the first administration of trial treatment). AEs occurring more than 60 days after last treatment administration were considered as treatment-emergent only if assessed as related to the trial treatment by the investigator. Serious adverse event (SAE): any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect or was another medically important condition. AE were graded for severity using NCI-CTCAE v5.0, where Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4 - Life-threatening consequences; and Grade 5: Death related to AE.
Time frame: From Baseline until 60 days after last dose of study treatment (3 years and 11 months)
Population: Analysis was performed on safety set that included all participants who received at least one dose of BNT411.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TESAE leading to Death | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TEAE | 2 Participants |
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related Grade >=3 TEAE | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TESAE leading to Death | 1 Participants |
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TEAE | 2 Participants |
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TESAE | 1 Participants |
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TESAE | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Grade >=3 TEAE | 1 Participants |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TESAE | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TEAE | 1 Participants |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TEAE | 1 Participants |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TESAE | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TESAE leading to Death | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related Grade >=3 TEAE | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TESAE leading to Death | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Grade >=3 TEAE | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TEAE | 1 Participants |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TESAE leading to Death | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Grade >=3 TEAE | 1 Participants |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TESAE | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TESAE | 1 Participants |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related Grade >=3 TEAE | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TESAE leading to Death | 1 Participants |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TEAE | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TESAE leading to Death | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TESAE | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TESAE | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TEAE | 2 Participants |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TESAE leading to Death | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related Grade >=3 TEAE | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Grade >=3 TEAE | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TEAE | 3 Participants |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TESAE leading to Death | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TEAE | 1 Participants |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TESAE leading to Death | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TESAE | 1 Participants |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TEAE | 4 Participants |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TESAE | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Grade >=3 TEAE | 3 Participants |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related Grade >=3 TEAE | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TESAE | 5 Participants |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related Grade >=3 TEAE | 2 Participants |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TESAE leading to Death | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TEAE | 14 Participants |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TESAE leading to Death | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TEAE | 13 Participants |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Grade >=3 TEAE | 3 Participants |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TESAE | 3 Participants |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Grade >=3 TEAE | 3 Participants |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TESAE | 1 Participants |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TEAE | 8 Participants |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TESAE leading to Death | 1 Participants |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related Grade >=3 TEAE | 2 Participants |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TESAE | 3 Participants |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TESAE leading to Death | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TEAE | 7 Participants |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Grade >=3 TEAE | 5 Participants |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TEAE | 6 Participants |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TESAE leading to Death | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TESAE | 4 Participants |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TEAE | 6 Participants |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TESAE leading to Death | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TESAE | 3 Participants |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related Grade >=3 TEAE | 3 Participants |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Grade >=3 TEAE | 5 Participants |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TESAE leading to Death | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TESAE | 3 Participants |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TEAE | 6 Participants |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TESAE | 3 Participants |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related Grade >=3 TEAE | 5 Participants |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TESAE leading to Death | 0 Participants |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TEAE | 6 Participants |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TESAE | 2 Participants |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related Grade >=3 TEAE | 3 Participants |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TESAE leading to Death | 1 Participants |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TESAE leading to Death | 1 Participants |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TEAE | 3 Participants |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TEAE | 3 Participants |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Grade >=3 TEAE | 3 Participants |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TESAE | 2 Participants |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TESAE | 3 Participants |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Grade >=3 TEAE | 3 Participants |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TEAE | 4 Participants |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TESAE leading to Death | 0 Participants |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TESAE leading to Death | 0 Participants |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related TESAE | 2 Participants |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | Related Grade >=3 TEAE | 3 Participants |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs | TEAE | 4 Participants |
Primary
Recommended Phase 2 Dose (RP2D) of BNT411
RP2D was based on integrated evaluation of safety, tolerability, clinical benefit, pharmacokinetic (PK), and pharmacodynamic data, for all dose levels was tested.
Time frame: Cycle 1 (21 days)
Population: Analysis was performed on DLT evaluable population. Data for this outcome measure was planned to be analyzed and reported for all participants collectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | Recommended Phase 2 Dose (RP2D) of BNT411 | 4.8 microgram/kilogram (mcg/kg) |
Secondary
Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last)
AUC0-last defined as the AUC from time 0 to the last measurable time-point was calculated from plasma concentrations of BNT411 using the linear-log trapezoidal method.
Time frame: Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days)
Population: Analysis was performed on PK evaluable set that included all participants who received at least one dose of BNT411 and have at least one quantifiable post-dose PK sample. Here, Overall number of participants analyzed = participants with available data for this outcome measure and number analyzed signifies participants with available data at respective visit and 0 in the number analyzed field signifies that no participants were available for analysis at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last) | Cycle 2 Day 1 | 327.1261 hours (h)*picogram (pg)/milliliters (mL) | Standard Deviation 143.16329 |
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last) | Cycle 1 Day 1 | 187.3477 hours (h)*picogram (pg)/milliliters (mL) | — |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last) | Cycle 2 Day 1 | 3341.8368 hours (h)*picogram (pg)/milliliters (mL) | — |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last) | Cycle 1 Day 1 | 1477.6656 hours (h)*picogram (pg)/milliliters (mL) | — |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last) | Cycle 2 Day 1 | 2313.8369 hours (h)*picogram (pg)/milliliters (mL) | — |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last) | Cycle 1 Day 1 | 3123.7583 hours (h)*picogram (pg)/milliliters (mL) | — |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last) | Cycle 2 Day 1 | 4635.3150 hours (h)*picogram (pg)/milliliters (mL) | Standard Deviation 3330.49325 |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last) | Cycle 1 Day 1 | 4724.5276 hours (h)*picogram (pg)/milliliters (mL) | Standard Deviation 3433.9448 |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last) | Cycle 2 Day 1 | 11745.1614 hours (h)*picogram (pg)/milliliters (mL) | Standard Deviation 2871.09499 |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last) | Cycle 1 Day 1 | 9445.2536 hours (h)*picogram (pg)/milliliters (mL) | Standard Deviation 3902.75812 |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last) | Cycle 2 Day 1 | 20998.2267 hours (h)*picogram (pg)/milliliters (mL) | Standard Deviation 11223.40206 |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last) | Cycle 1 Day 1 | 18735.9783 hours (h)*picogram (pg)/milliliters (mL) | Standard Deviation 11750.72661 |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last) | Cycle 1 Day 1 | 22365.2916 hours (h)*picogram (pg)/milliliters (mL) | Standard Deviation 8763.3741 |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last) | Cycle 2 Day 1 | 18392.6594 hours (h)*picogram (pg)/milliliters (mL) | Standard Deviation 7546.26734 |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last) | Cycle 2 Day 1 | 26266.1125 hours (h)*picogram (pg)/milliliters (mL) | Standard Deviation 18091.16303 |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last) | Cycle 1 Day 1 | 49384.9308 hours (h)*picogram (pg)/milliliters (mL) | Standard Deviation 31393.75269 |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last) | Cycle 1 Day 1 | 29680.3554 hours (h)*picogram (pg)/milliliters (mL) | Standard Deviation 12850.18934 |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last) | Cycle 2 Day 1 | 28693.3094 hours (h)*picogram (pg)/milliliters (mL) | Standard Deviation 7377.64393 |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last) | Cycle 1 Day 2 | 3604.2235 hours (h)*picogram (pg)/milliliters (mL) | Standard Deviation 1804.20847 |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last) | Cycle 2 Day 2 | 3543.6926 hours (h)*picogram (pg)/milliliters (mL) | Standard Deviation 4508.63205 |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last) | Cycle 1 Day 2 | 6258.0743 hours (h)*picogram (pg)/milliliters (mL) | Standard Deviation 1565.55574 |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last) | Cycle 2 Day 2 | 3369.5271 hours (h)*picogram (pg)/milliliters (mL) | — |
Secondary
PK Assessment for BNT411: Clearance (CL)
Clearance reflects the elimination of the drug from the body was estimated from plasma concentrations of BNT411 as Dose/AUC0-inf. Dose was converted, as necessary, to reflect the amount of anhydrous BNT411 administered.
Time frame: Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days)
Population: Analysis was performed on PK evaluable set. Here, Overall number of participants analyzed = participants with available data for this outcome measure and number analyzed signifies participants with available data at respective visit and 0 in the number analyzed field signifies that no participants were available for analysis at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | PK Assessment for BNT411: Clearance (CL) | Cycle 1 Day 1 | 27.6502 liters (L)/hours (h) | — |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | PK Assessment for BNT411: Clearance (CL) | Cycle 2 Day 1 | 3.5213 liters (L)/hours (h) | — |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | PK Assessment for BNT411: Clearance (CL) | Cycle 1 Day 1 | 8.3063 liters (L)/hours (h) | — |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | PK Assessment for BNT411: Clearance (CL) | Cycle 1 Day 1 | 13.1362 liters (L)/hours (h) | — |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | PK Assessment for BNT411: Clearance (CL) | Cycle 2 Day 1 | 17.6849 liters (L)/hours (h) | — |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Clearance (CL) | Cycle 2 Day 1 | 28.0090 liters (L)/hours (h) | Standard Deviation 14.49788 |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Clearance (CL) | Cycle 1 Day 1 | 36.6351 liters (L)/hours (h) | Standard Deviation 34.6309 |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Clearance (CL) | Cycle 2 Day 1 | 13.9638 liters (L)/hours (h) | Standard Deviation 2.28039 |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Clearance (CL) | Cycle 1 Day 1 | 21.1677 liters (L)/hours (h) | Standard Deviation 8.415 |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | PK Assessment for BNT411: Clearance (CL) | Cycle 2 Day 1 | 22.2684 liters (L)/hours (h) | Standard Deviation 13.53332 |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | PK Assessment for BNT411: Clearance (CL) | Cycle 1 Day 1 | 23.6285 liters (L)/hours (h) | Standard Deviation 9.44317 |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | PK Assessment for BNT411: Clearance (CL) | Cycle 1 Day 1 | 24.7574 liters (L)/hours (h) | Standard Deviation 24.89704 |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | PK Assessment for BNT411: Clearance (CL) | Cycle 2 Day 1 | 25.7574 liters (L)/hours (h) | Standard Deviation 14.62545 |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | PK Assessment for BNT411: Clearance (CL) | Cycle 1 Day 1 | 13.4479 liters (L)/hours (h) | Standard Deviation 6.36326 |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | PK Assessment for BNT411: Clearance (CL) | Cycle 2 Day 1 | 20.8883 liters (L)/hours (h) | Standard Deviation 3.90723 |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | PK Assessment for BNT411: Clearance (CL) | Cycle 1 Day 1 | 24.4680 liters (L)/hours (h) | Standard Deviation 9.09568 |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | PK Assessment for BNT411: Clearance (CL) | Cycle 2 Day 1 | 21.9203 liters (L)/hours (h) | Standard Deviation 10.72759 |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Clearance (CL) | Cycle 1 Day 2 | 20.5762 liters (L)/hours (h) | Standard Deviation 10.33093 |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Clearance (CL) | Cycle 2 Day 2 | 14.3209 liters (L)/hours (h) | — |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Clearance (CL) | Cycle 1 Day 2 | 30.8326 liters (L)/hours (h) | Standard Deviation 5.92557 |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Clearance (CL) | Cycle 2 Day 2 | 38.3186 liters (L)/hours (h) | — |
Secondary
PK Assessment for BNT411: Maximum Plasma Concentration (Cmax)
Cmax defined as the maximum observed plasma concentration was estimated from plasma concentrations of BNT411.
Time frame: Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days)
Population: Analysis was performed on the PK evaluable set. Here, Overall number of participants analyzed = participants with available data for this outcome measure and number analyzed signifies participants with available data at respective visit and 0 in the number analyzed field signifies that no participants were available for analysis at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | PK Assessment for BNT411: Maximum Plasma Concentration (Cmax) | Cycle 2 Day 1 | 254.0 picogram/milliliters (pg/mL) | Standard Deviation 57.98 |
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | PK Assessment for BNT411: Maximum Plasma Concentration (Cmax) | Cycle 1 Day 1 | 152.0 picogram/milliliters (pg/mL) | — |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | PK Assessment for BNT411: Maximum Plasma Concentration (Cmax) | Cycle 1 Day 1 | 1020.0 picogram/milliliters (pg/mL) | — |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | PK Assessment for BNT411: Maximum Plasma Concentration (Cmax) | Cycle 2 Day 1 | 2163.0 picogram/milliliters (pg/mL) | — |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | PK Assessment for BNT411: Maximum Plasma Concentration (Cmax) | Cycle 2 Day 1 | 1520.0 picogram/milliliters (pg/mL) | — |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | PK Assessment for BNT411: Maximum Plasma Concentration (Cmax) | Cycle 1 Day 1 | 2437.0 picogram/milliliters (pg/mL) | — |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Maximum Plasma Concentration (Cmax) | Cycle 1 Day 1 | 3229.3 picogram/milliliters (pg/mL) | Standard Deviation 1847.84 |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Maximum Plasma Concentration (Cmax) | Cycle 2 Day 1 | 2947.3 picogram/milliliters (pg/mL) | Standard Deviation 1281.14 |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Maximum Plasma Concentration (Cmax) | Cycle 2 Day 1 | 8104.7 picogram/milliliters (pg/mL) | Standard Deviation 1473.43 |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Maximum Plasma Concentration (Cmax) | Cycle 1 Day 1 | 8191.3 picogram/milliliters (pg/mL) | Standard Deviation 3211.56 |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | PK Assessment for BNT411: Maximum Plasma Concentration (Cmax) | Cycle 1 Day 1 | 13005.9 picogram/milliliters (pg/mL) | Standard Deviation 4681.33 |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | PK Assessment for BNT411: Maximum Plasma Concentration (Cmax) | Cycle 2 Day 1 | 14804.4 picogram/milliliters (pg/mL) | Standard Deviation 6042.78 |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | PK Assessment for BNT411: Maximum Plasma Concentration (Cmax) | Cycle 2 Day 1 | 13800.0 picogram/milliliters (pg/mL) | Standard Deviation 3642.8 |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | PK Assessment for BNT411: Maximum Plasma Concentration (Cmax) | Cycle 1 Day 1 | 20404.6 picogram/milliliters (pg/mL) | Standard Deviation 8137.2 |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | PK Assessment for BNT411: Maximum Plasma Concentration (Cmax) | Cycle 1 Day 1 | 31596.8 picogram/milliliters (pg/mL) | Standard Deviation 10260.05 |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | PK Assessment for BNT411: Maximum Plasma Concentration (Cmax) | Cycle 2 Day 1 | 19551.8 picogram/milliliters (pg/mL) | Standard Deviation 16904.3 |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | PK Assessment for BNT411: Maximum Plasma Concentration (Cmax) | Cycle 1 Day 1 | 25967.7 picogram/milliliters (pg/mL) | Standard Deviation 10270.43 |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | PK Assessment for BNT411: Maximum Plasma Concentration (Cmax) | Cycle 2 Day 1 | 22547.8 picogram/milliliters (pg/mL) | Standard Deviation 7933.89 |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Maximum Plasma Concentration (Cmax) | Cycle 1 Day 2 | 2880.33 picogram/milliliters (pg/mL) | Standard Deviation 2065.462 |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Maximum Plasma Concentration (Cmax) | Cycle 2 Day 2 | 2993.95 picogram/milliliters (pg/mL) | Standard Deviation 4214.427 |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Maximum Plasma Concentration (Cmax) | Cycle 2 Day 2 | 2900.00 picogram/milliliters (pg/mL) | — |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Maximum Plasma Concentration (Cmax) | Cycle 1 Day 2 | 5598.25 picogram/milliliters (pg/mL) | Standard Deviation 766.713 |
Secondary
PK Assessment for BNT411: Terminal Elimination Half-life (T1/2)
Terminal elimination half-life was estimated from the plasma concentrations of BNT411.
Time frame: Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days)
Population: Analysis was performed on PK evaluable set. Here, Overall number of participants analyzed = participants with available data for this outcome measure and number analyzed signifies participants with available data at respective visit and 0 in the number analyzed field signifies that no participants were available for analysis at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | PK Assessment for BNT411: Terminal Elimination Half-life (T1/2) | Cycle 1 Day 1 | 1.8937 hours (h) | — |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | PK Assessment for BNT411: Terminal Elimination Half-life (T1/2) | Cycle 2 Day 1 | 3.6803 hours (h) | — |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | PK Assessment for BNT411: Terminal Elimination Half-life (T1/2) | Cycle 1 Day 1 | 3.9279 hours (h) | — |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | PK Assessment for BNT411: Terminal Elimination Half-life (T1/2) | Cycle 1 Day 1 | 5.7077 hours (h) | — |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | PK Assessment for BNT411: Terminal Elimination Half-life (T1/2) | Cycle 2 Day 1 | 6.2500 hours (h) | — |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Terminal Elimination Half-life (T1/2) | Cycle 2 Day 1 | 4.9020 hours (h) | Standard Deviation 0.57744 |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Terminal Elimination Half-life (T1/2) | Cycle 1 Day 1 | 5.2525 hours (h) | Standard Deviation 0.99582 |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Terminal Elimination Half-life (T1/2) | Cycle 1 Day 1 | 7.4679 hours (h) | Standard Deviation 1.87347 |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Terminal Elimination Half-life (T1/2) | Cycle 2 Day 1 | 6.3386 hours (h) | Standard Deviation 0.73577 |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | PK Assessment for BNT411: Terminal Elimination Half-life (T1/2) | Cycle 2 Day 1 | 6.0603 hours (h) | Standard Deviation 1.18916 |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | PK Assessment for BNT411: Terminal Elimination Half-life (T1/2) | Cycle 1 Day 1 | 7.4600 hours (h) | Standard Deviation 4.30673 |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | PK Assessment for BNT411: Terminal Elimination Half-life (T1/2) | Cycle 1 Day 1 | 5.1189 hours (h) | Standard Deviation 1.23014 |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | PK Assessment for BNT411: Terminal Elimination Half-life (T1/2) | Cycle 2 Day 1 | 4.9479 hours (h) | Standard Deviation 1.51079 |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | PK Assessment for BNT411: Terminal Elimination Half-life (T1/2) | Cycle 1 Day 1 | 8.7346 hours (h) | Standard Deviation 4.71577 |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | PK Assessment for BNT411: Terminal Elimination Half-life (T1/2) | Cycle 2 Day 1 | 6.2166 hours (h) | Standard Deviation 0.45957 |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | PK Assessment for BNT411: Terminal Elimination Half-life (T1/2) | Cycle 1 Day 1 | 6.2721 hours (h) | Standard Deviation 0.48131 |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | PK Assessment for BNT411: Terminal Elimination Half-life (T1/2) | Cycle 2 Day 1 | 4.5667 hours (h) | Standard Deviation 2.07892 |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Terminal Elimination Half-life (T1/2) | Cycle 2 Day 2 | 6.0880 hours (h) | — |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Terminal Elimination Half-life (T1/2) | Cycle 1 Day 2 | 4.8989 hours (h) | Standard Deviation 1.68795 |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Terminal Elimination Half-life (T1/2) | Cycle 2 Day 2 | 4.4110 hours (h) | — |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Terminal Elimination Half-life (T1/2) | Cycle 1 Day 2 | 4.7244 hours (h) | Standard Deviation 0.68988 |
Secondary
PK Assessment for BNT411: Time to Reach Cmax (Tmax)
Tmax defined as the time to reach maximum (peak) concentration was estimated from plasma concentrations of BNT411.
Time frame: Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days)
Population: Analysis was performed on the PK evaluable set. Here, Overall number of participants analyzed = participants with available data for this outcome measure and number analyzed signifies participants with available data at respective visit and 0 in the number analyzed field signifies that no participants were available for analysis at the specified visit.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | PK Assessment for BNT411: Time to Reach Cmax (Tmax) | Cycle 2 Day 1 | 0.5750 hours (h) |
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | PK Assessment for BNT411: Time to Reach Cmax (Tmax) | Cycle 1 Day 1 | 0.7667 hours (h) |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | PK Assessment for BNT411: Time to Reach Cmax (Tmax) | Cycle 1 Day 1 | 0.5000 hours (h) |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | PK Assessment for BNT411: Time to Reach Cmax (Tmax) | Cycle 2 Day 1 | 0.5000 hours (h) |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | PK Assessment for BNT411: Time to Reach Cmax (Tmax) | Cycle 2 Day 1 | 0.5833 hours (h) |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | PK Assessment for BNT411: Time to Reach Cmax (Tmax) | Cycle 1 Day 1 | 0.5667 hours (h) |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Time to Reach Cmax (Tmax) | Cycle 1 Day 1 | 0.6500 hours (h) |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Time to Reach Cmax (Tmax) | Cycle 2 Day 1 | 0.5833 hours (h) |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Time to Reach Cmax (Tmax) | Cycle 1 Day 1 | 0.5417 hours (h) |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Time to Reach Cmax (Tmax) | Cycle 2 Day 1 | 0.5000 hours (h) |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | PK Assessment for BNT411: Time to Reach Cmax (Tmax) | Cycle 1 Day 1 | 0.5917 hours (h) |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | PK Assessment for BNT411: Time to Reach Cmax (Tmax) | Cycle 2 Day 1 | 0.6000 hours (h) |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | PK Assessment for BNT411: Time to Reach Cmax (Tmax) | Cycle 1 Day 1 | 0.6000 hours (h) |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | PK Assessment for BNT411: Time to Reach Cmax (Tmax) | Cycle 2 Day 1 | 0.6167 hours (h) |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | PK Assessment for BNT411: Time to Reach Cmax (Tmax) | Cycle 1 Day 1 | 0.5417 hours (h) |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | PK Assessment for BNT411: Time to Reach Cmax (Tmax) | Cycle 2 Day 1 | 0.6333 hours (h) |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | PK Assessment for BNT411: Time to Reach Cmax (Tmax) | Cycle 1 Day 1 | 0.6000 hours (h) |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | PK Assessment for BNT411: Time to Reach Cmax (Tmax) | Cycle 2 Day 1 | 0.6417 hours (h) |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Time to Reach Cmax (Tmax) | Cycle 1 Day 2 | 0.5833 hours (h) |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Time to Reach Cmax (Tmax) | Cycle 2 Day 2 | 13.1083 hours (h) |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Time to Reach Cmax (Tmax) | Cycle 1 Day 2 | 0.6000 hours (h) |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Time to Reach Cmax (Tmax) | Cycle 2 Day 2 | 0.5833 hours (h) |
Secondary
PK Assessment for BNT411: Trough Concentration (Ctrough)
Ctrough defined as the pre-dose concentrations of BNT411 was estimated from the plasma concentrations of BNT411.
Time frame: Part 1A: Start of infusion on Cycle 1 Day 8, Day 15, Day 22, Day 43; Day 85; Part 1B: Start of infusion on Cycle 1 Day 8, Day 15, Day 23, Day 44 (each cycle duration=21 days)
Population: Analysis was performed on PK evaluable set. Here, Overall number of participants analyzed = participants with available data for this outcome measure and number analyzed signifies participants with available data at respective visit and 0 in the number analyzed field signifies that no participants were available for analysis at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 43 | 0.000 picogram/milliliters (pg/mL) | — |
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 15 | 8.400 picogram/milliliters (pg/mL) | Standard Deviation 11.8794 |
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 22 | 0.000 picogram/milliliters (pg/mL) | Standard Deviation 0 |
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 8 | 0.000 picogram/milliliters (pg/mL) | — |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 8 | 0.000 picogram/milliliters (pg/mL) | — |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 8 | 0.000 picogram/milliliters (pg/mL) | — |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 22 | 0.000 picogram/milliliters (pg/mL) | — |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 15 | 0.000 picogram/milliliters (pg/mL) | — |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 43 | 4.833 picogram/milliliters (pg/mL) | Standard Deviation 8.3716 |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 85 | 0.590 picogram/milliliters (pg/mL) | Standard Deviation 0.8344 |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 15 | 0.000 picogram/milliliters (pg/mL) | Standard Deviation 0 |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 8 | 0.000 picogram/milliliters (pg/mL) | Standard Deviation 0 |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 22 | 51.500 picogram/milliliters (pg/mL) | Standard Deviation 72.832 |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 43 | 0.000 picogram/milliliters (pg/mL) | — |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 15 | 0.253 picogram/milliliters (pg/mL) | Standard Deviation 0.505 |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 22 | 0.000 picogram/milliliters (pg/mL) | Standard Deviation 0 |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 8 | 0.000 picogram/milliliters (pg/mL) | — |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 15 | 0.168 picogram/milliliters (pg/mL) | Standard Deviation 0.4123 |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 22 | 0.000 picogram/milliliters (pg/mL) | Standard Deviation 0 |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 43 | 0.370 picogram/milliliters (pg/mL) | Standard Deviation 0.6409 |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 8 | 0.476 picogram/milliliters (pg/mL) | Standard Deviation 0.9789 |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 22 | 0.000 picogram/milliliters (pg/mL) | Standard Deviation 0 |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 8 | 0.000 picogram/milliliters (pg/mL) | Standard Deviation 0 |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 43 | 0.000 picogram/milliliters (pg/mL) | — |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 85 | 38500.000 picogram/milliliters (pg/mL) | — |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 15 | 0.580 picogram/milliliters (pg/mL) | Standard Deviation 0.6722 |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 85 | 1.170 picogram/milliliters (pg/mL) | — |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 43 | 0.970 picogram/milliliters (pg/mL) | Standard Deviation 1.3718 |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 22 | 1.770 picogram/milliliters (pg/mL) | — |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 8 | 0.000 picogram/milliliters (pg/mL) | Standard Deviation 0 |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 15 | 1.350 picogram/milliliters (pg/mL) | Standard Deviation 0.297 |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 43 | 1.690 picogram/milliliters (pg/mL) | — |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 15 | 1.655 picogram/milliliters (pg/mL) | Standard Deviation 0.5303 |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 85 | 0.000 picogram/milliliters (pg/mL) | — |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 8 | 0.000 picogram/milliliters (pg/mL) | Standard Deviation 0 |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 22 | 0.000 picogram/milliliters (pg/mL) | — |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 8 | 0.0 picogram/milliliters (pg/mL) | Standard Deviation 0 |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 15 | 0.0 picogram/milliliters (pg/mL) | — |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 44 | 0.0 picogram/milliliters (pg/mL) | — |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 15 | 0.0 picogram/milliliters (pg/mL) | Standard Deviation 0 |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 23 | 0.0 picogram/milliliters (pg/mL) | — |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 44 | 0.0 picogram/milliliters (pg/mL) | — |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Trough Concentration (Ctrough) | Cycle 1 Day 8 | 0.0 picogram/milliliters (pg/mL) | — |
Secondary
PK Assessment for BNT411: Volume of Distribution (Vd)
Volume of distribution (Vd) is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vd was estimated from plasma concentrations of BNT411.
Time frame: Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days)
Population: Analysis was performed on PK evaluable set. Here, Overall number of participants analyzed = participants with available data for this outcome measure and number analyzed signifies participants with available data at respective visit and 0 in the number analyzed field signifies that no participants were available for analysis at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg | PK Assessment for BNT411: Volume of Distribution (Vd) | Cycle 1 Day 1 | 75.5414 liters (L) | — |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | PK Assessment for BNT411: Volume of Distribution (Vd) | Cycle 2 Day 1 | 18.6963 liters (L) | — |
| Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg | PK Assessment for BNT411: Volume of Distribution (Vd) | Cycle 1 Day 1 | 47.0697 liters (L) | — |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | PK Assessment for BNT411: Volume of Distribution (Vd) | Cycle 1 Day 1 | 108.1691 liters (L) | — |
| Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg | PK Assessment for BNT411: Volume of Distribution (Vd) | Cycle 2 Day 1 | 159.4620 liters (L) | — |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Volume of Distribution (Vd) | Cycle 2 Day 1 | 194.0698 liters (L) | Standard Deviation 97.37669 |
| Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Volume of Distribution (Vd) | Cycle 1 Day 1 | 296.6890 liters (L) | Standard Deviation 313.18628 |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Volume of Distribution (Vd) | Cycle 2 Day 1 | 127.2646 liters (L) | Standard Deviation 21.21154 |
| Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Volume of Distribution (Vd) | Cycle 1 Day 1 | 220.7140 liters (L) | Standard Deviation 74.05373 |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | PK Assessment for BNT411: Volume of Distribution (Vd) | Cycle 1 Day 1 | 232.0475 liters (L) | Standard Deviation 100.1955 |
| Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg | PK Assessment for BNT411: Volume of Distribution (Vd) | Cycle 2 Day 1 | 187.7812 liters (L) | Standard Deviation 96.09022 |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | PK Assessment for BNT411: Volume of Distribution (Vd) | Cycle 2 Day 1 | 163.0226 liters (L) | Standard Deviation 44.35908 |
| Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg | PK Assessment for BNT411: Volume of Distribution (Vd) | Cycle 1 Day 1 | 168.7668 liters (L) | Standard Deviation 145.45978 |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | PK Assessment for BNT411: Volume of Distribution (Vd) | Cycle 2 Day 1 | 186.4341 liters (L) | Standard Deviation 31.41644 |
| Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg | PK Assessment for BNT411: Volume of Distribution (Vd) | Cycle 1 Day 1 | 156.7781 liters (L) | Standard Deviation 77.21878 |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | PK Assessment for BNT411: Volume of Distribution (Vd) | Cycle 1 Day 1 | 222.3040 liters (L) | Standard Deviation 85.88236 |
| Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg | PK Assessment for BNT411: Volume of Distribution (Vd) | Cycle 2 Day 1 | 148.4863 liters (L) | Standard Deviation 125.70109 |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Volume of Distribution (Vd) | Cycle 1 Day 2 | 132.8456 liters (L) | Standard Deviation 22.90794 |
| Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg | PK Assessment for BNT411: Volume of Distribution (Vd) | Cycle 2 Day 2 | 125.7815 liters (L) | — |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Volume of Distribution (Vd) | Cycle 2 Day 2 | 243.8492 liters (L) | — |
| Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg | PK Assessment for BNT411: Volume of Distribution (Vd) | Cycle 1 Day 2 | 205.7365 liters (L) | Standard Deviation 14.86844 |