Safety and preliminary efficacy of BNT314 in cancer patients with malignant solid tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

BioNTech SE

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 Aug 2024 → ongoing

Decision date (initial)

2024-04-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

BionTech SE

External identifiers

EU CT number

2023-506053-38-00

ClinicalTrials.gov

NCT06150183

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Dose response, Efficacy, Safety

To determine the maximum tolerated dose (MTD) / maximum administered dose (MAD) of BNT314 administered as monotherapy. To establish the safety profile of BNT314 administered as monotherapy.

Secondary objectives 3

1. To characterize the pharmacokinetics (PK) of BNT314 administered as monotherapy.
2. To characterize the immunogenicity of BNT314 administered as monotherapy.
3. To evaluate the preliminary antitumor activity of BNT314 administered as monotherapy based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Conditions and MedDRA coding

Advanced or metastatic malignant solid tumors

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 19

1. Have the ability to voluntarily give informed consent by signing and dating the informed consent form (ICF) before initiation of any trial-specific procedures.
2. Have adequate renal function at screening as determined by: Glomerular filtration rate (GFR) ≥45 mL/min/1.73 m² according to the abbreviated Modification of Diet in Renal Disease equation.
3. Have adequate pancreas function at screening as determined by serum amylase and lipase with no signs and symptoms of pancreatitis.
4. Patients of childbearing potential (POCBP) must have a negative urine and serum beta human chorionic gonadotropin (beta-hCG) test at screening.
5. 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 60 days after receiving the last trial treatment.
6. POCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during trial, starting at Visit D1 and thereafter until 60 d after receiving the last trial treatment.
7. Men 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 trial, starting at Visit D1 and thereafter until 90 d after receiving the last trial treatment.
8. Men must be willing to refrain from sperm donation, starting at Visit D1 and thereafter until 90 days (one sperm cycle) after receiving the last trial treatment.
9. Inclusion criteria for monotherapy dose escalation only: 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.
10. Inclusion criteria for backfill cohorts only: Patients with previously documented metastatic or advanced malignant solid tumor of selected cancers who have received at least one prior therapy for locally advanced/unresectable and/or metastatic disease.
11. Inclusion criteria for combination therapy SRI and dose expansion only. For patients in Expansion Cohort 1: Patients with histologically confirmed locally advanced/unresectable and/or metastatic selected cancer. With documented PD on or after standard therapy.
12. Are willing and able to comply with scheduled visits, treatment schedule, laboratory tests, lifestyle restrictions, and other requirements of the trial. This includes that they are able to understand and follow trial-related instructions.
13. Are ≥18 years of age at the time of giving informed consent.
14. Have measurable disease according to RECIST v1.1
15. Have a life expectancy of >3 months.
16. Have ECOG performance score of 0 or 1 at screening.
17. Have adequate coagulation function at screening as determined by: International normalized ratio (INR) or prothrombin time ≤1.5×upper limit normal (ULN). Activated partial thromboplastin time (aPTT) ≤1.5×ULN.
18. Have adequate bone marrow/hematologic function at screening as determined by: Absolute neutrophil count (ANC) ≥1.5×10E9/L (≥1500/μL). Platelet count ≥100×10E9/L (≥100,000/μL). Hemoglobin ≥9 g/dL.
19. Have adequate hepatic function at screening as determined by: Total bilirubin ≤1.5×ULN OR direct bilirubin ≤ULN for patients with total bilirubin levels >1.5×ULN. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 ULN for patients with or without liver metastases. Albumin ≥30 g/L.

Exclusion criteria 7

1. Patients are not eligible for enrollment in this trial if any of the following criteria apply: 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 (AF) will be allowed. • History of arterial thrombosis or pulmonary embolism within six months before the first dose of trial treatment. • History of myocardial infarction within six months before the first dose of trial 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[1]related AEs (irAEs). • History of: Grade 2 immune mediated myocarditis/colitis/pneumonitis that led to CPI discontinuation. Patients experiencing other Grade 2 immune mediated AEs that led to CPI discontinuation, require discussion with the sponsor. Any Grade ≥3 immune mediated AEs that led to CPI discontinuation. − Patients with Grade 3 AEs that led to CPI discontinuation but resolved within 21 days without sequalae may also be considered for discussion with the sponsor. • 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 trial 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 six weeks prior to C1D1. • Serious, non-healing wound, skin ulcer (of any grade), or bone fracture will be excluded
2. Prior therapy: Radiotherapy within 14 days prior to first BNT314 administration. Palliative radiotherapy will be allowed, but not to target lesions. Any EpCAM- or 4-1BB-targeting treatment. Treatment with an anti-cancer agent within 4 weeks or for systemic therapies after at least 5 half-lives of the drug, whichever is shorter, prior to trial treatment administration. Patient has received any investigational agent or used an invasive investigational medical device within 28 days before the planned first dose of BNT314 or is currently enrolled in an interventional trial. 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 two weeks prior to first BNT314 administration or is chronically transfusion dependent. Any positive test for hepatitis B, indicating acute or chronic infection. Any positive test for hepatitis C, indicating acute or chronic infection. Received any live vaccine within 30 days prior to the start of trial treatment.
3. Known alcohol dependency within 6 months enrolment in this trial.
4. Planned enrolment in another trial of an IMP, starting after Visit D1 and continuously until the last planned visit in this trial.
5. Have a medical, psychological, or social condition which, in the opinion of the investigator, could compromise their wellbeing if they participate in the trial, or that could prevent, limit, or confound the protocol specified assessments or procedures, or that could impact adherence to protocol described requirements.
6. Are subject to exclusion periods from another investigational trial.
7. Are vulnerable individuals as per International Council for Harmonisation (ICH) E6 definition.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Dose escalation only: In patients receiving at least one dose of BNT314 and evaluable for DLT: Occurrence of DLTs within a cohort during the DLT evaluation period.
2. In patients receiving at least one dose of BNT314, from first dose of trial treatment to 90 days after last dose of trial treatment, per cohort, number, and proportion of patients with: Occurrence of treatment-emergent adverse events (TEAEs) including Grade ≥ 3, serious, fatal TEAE by relationship.
3. In patients receiving at least one dose of BNT314, from first dose of trial treatment to 90 days after last dose of trial treatment, per cohort, number, and proportion of patients with: Occurrence of dose reduction and discontinuation of IMP due to TEAE.
4. In patients receiving at least one dose of BNT314, from first dose of trial treatment to 90 days after last dose of trial treatment, per cohort, number, and proportion of patients with: Occurrence of Grade≥3 abnormal safety laboratory parameters.

Secondary endpoints 6

1. In patients receiving at least one dose of BNT314 and evaluable for PK, per cohort, geometric means for the following PK parameters: Area under the concentration-time curve from pre-dose to last quantifiable time point prior to the next dose (AUClast) and from pre-dose to the end of the dosing period (AUCtau).
2. In patients receiving at least one dose of BNT314 and evaluable for PK, per cohort, geometric means for the following PK parameters: Maximum concentration (Cmax) from pre-dose to the end of the dosing period.
3. In patients receiving at least one dose of BNT314, per cohort, number and proportion of patients who developed detectable anti-drug antibody (ADA) from baseline to the end of trial treatment.
4. In patients receiving at least one dose of BNT314: Disease control rate (DCR) based on investigator’s tumor assessment according to RECIST 1.1 is reported with number and proportion of patients with a complete response (CR), partial response (PR), or stable disease (SD) (assessed at least 6 weeks after first dose of trial treatment) as best overall response.
5. In patients receiving at least one dose of BNT314: Objective response rate (ORR) based on investigator’s tumor assessment according to RECIST 1.1 is reported with number and proportion of patients with a confirmed CR or PR as best overall response.
6. In patients receiving at least one dose of BNT314: In patients with confirmed CR or PR assessment, duration of response (DOR) based on investigator’s tumor assessment according to RECIST 1.1 is defined as the time from first objective response (CR or PR) to first occurrence of objective tumor progression or death from any cause, whichever occurs first.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

BioNTech SE

Sponsor organisation

BioNTech SE

Address

An Der Goldgrube 12, Oberstadt Oberstadt

City

Mainz

Postcode

55131

Country

Germany

Scientific contact point

Organisation

BioNTech SE

Contact name

Clinical Trial Information Desk

Public contact point

Organisation

BioNTech SE

Contact name

Clinical Trial Information Desk

Third parties 16

Locations

3 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 21 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications