Trial Outcomes & Findings for Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy Trial of BNT141 in Patients With Unresectable or Metastatic CLDN18.2-positive Gastric, Pancreatic, Ovarian and Biliary Tract Tumors (NCT NCT04683939)

Last Updated: 2024-10-02

Results Overview

All TEAEs are included, i.e., AEs with an onset date on or after the first dose of BNT141 (if the AE was absent before the first dose) or worsened after the first dose of BNT141 (if the AE was present before the first dose). AEs with an onset date \>60 days after the last dose of BNT141 are included only if assessed as related to BNT141 by the investigator. Intensity of AEs was graded according to the NCI CTCAE v5.0, i.e.,: Grade 1 - Mild, Grade 2 - Moderate, Grade 3 - Severe, Grade 4 - Life-threatening consequences; urgent urgent intervention indicated, Grade 5 - Death related to AE

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

13 participants

Primary outcome timeframe

From start of BNT141 treatment until the second Safety Follow-up Visit (60 ± 7 days after last dose), up to 30 weeks.

Results posted on

2024-10-02

Participant Flow

A total of 15 patients (6 from Canada and 9 from the USA) were screened while 13 patients (5 patients and 8 patients respectively from two countries) were enrolled in this study and 2 patients failed screening (primary reason inclusion/exclusion criteria not met). All patients were enrolled into Part 1A of this study and received BNT141.

Adult patients with CLDN18.2-positive tumors. CLDN18.2 positivity was determined by a central laboratory during the pre-screening phase using a validated immunohistochemistry assay and was defined as moderate (50-75%)-to-strong (more than 75%) CLDN18.2 expression. No participant was enrolled in the planned Part 1B and Part 2 of this study.

Participant milestones

Participant milestones
Measure	BNT141 Monotherapy - 0.15 mg/kg The number of patients from Part 1A treated with BNT141 0.15 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.30 mg/kg The number of patients from Part 1A treated with BNT141 0.30 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.45 mg/kg The number of patients from Part 1A treated with BNT141 0.45 mg/kg, corresponding to an intermediate dose level. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.60 mg/kg The number of patients from Part 1A treated with BNT141 0.60 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.
Overall Study STARTED	3	3	4	3
Overall Study COMPLETED	0	0	0	0
Overall Study NOT COMPLETED	3	3	4	3

Reasons for withdrawal

Reasons for withdrawal
Measure	BNT141 Monotherapy - 0.15 mg/kg The number of patients from Part 1A treated with BNT141 0.15 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.30 mg/kg The number of patients from Part 1A treated with BNT141 0.30 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.45 mg/kg The number of patients from Part 1A treated with BNT141 0.45 mg/kg, corresponding to an intermediate dose level. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.60 mg/kg The number of patients from Part 1A treated with BNT141 0.60 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.
Overall Study Study termination by the sponsor	0	1	2	2
Overall Study Death	1	1	2	1
Overall Study Withdrawal by Subject	1	0	0	0
Overall Study Physician Decision	1	0	0	0
Overall Study Lost to Follow-up	0	1	0	0

Baseline Characteristics

Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy Trial of BNT141 in Patients With Unresectable or Metastatic CLDN18.2-positive Gastric, Pancreatic, Ovarian and Biliary Tract Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BNT141 Monotherapy - 0.15 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.15 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.30 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.30 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.45 mg/kg n=4 Participants The number of patients from Part 1A treated with BNT141 0.45 mg/kg, corresponding to an intermediate dose level. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.60 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.60 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	Total n=13 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	4 Participants n=21 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	9 Participants n=21 Participants
Age, Continuous	56.0 years STANDARD_DEVIATION 15.52 • n=5 Participants	73.7 years STANDARD_DEVIATION 7.02 • n=7 Participants	58.3 years STANDARD_DEVIATION 11.35 • n=5 Participants	74.0 years STANDARD_DEVIATION 6.24 • n=4 Participants	64.9 years STANDARD_DEVIATION 12.71 • n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	10 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	12 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment Canada	0 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants	5 participants n=21 Participants
Region of Enrollment United States	3 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	1 participants n=4 Participants	8 participants n=21 Participants
Eastern Cooperative Oncology Group performance score (ECOG PS) ECOG PS 0	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	4 Participants n=21 Participants
Eastern Cooperative Oncology Group performance score (ECOG PS) ECOG PS 1	3 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	9 Participants n=21 Participants
Eastern Cooperative Oncology Group performance score (ECOG PS) ECOG PS 2	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Body Mass Index (BMI)	32.56 kg/m^2 STANDARD_DEVIATION 7.120 • n=5 Participants	24.41 kg/m^2 STANDARD_DEVIATION 1.541 • n=7 Participants	20.46 kg/m^2 STANDARD_DEVIATION 4.888 • n=5 Participants	24.67 kg/m^2 STANDARD_DEVIATION 5.530 • n=4 Participants	25.14 kg/m^2 STANDARD_DEVIATION 6.42 • n=21 Participants
Number of prior systemic cancer therapies per patient	3.7 number of therapies STANDARD_DEVIATION 1.15 • n=5 Participants	3.3 number of therapies STANDARD_DEVIATION 2.52 • n=7 Participants	3.8 number of therapies STANDARD_DEVIATION 0.50 • n=5 Participants	1.7 number of therapies STANDARD_DEVIATION 0.58 • n=4 Participants	3.2 number of therapies STANDARD_DEVIATION 1.46 • n=21 Participants

PRIMARY outcome

Timeframe: From start of BNT141 treatment until the second Safety Follow-up Visit (60 ± 7 days after last dose), up to 30 weeks.

Population: Safety Set - All patients who received investigational medicinal product (IMP) (i.e., at least one dose of BNT141)

Outcome measures

Outcome measures
Measure	BNT141 Monotherapy - 0.15 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.15 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.30 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.30 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.45 mg/kg n=4 Participants The number of patients from Part 1A treated with BNT141 0.45 mg/kg, corresponding to an intermediate dose level. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.60 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.60 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.
Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship Any TEAE	3 participants	3 participants	4 participants	3 participants
Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship Any serious TEAE	1 participants	1 participants	1 participants	2 participants
Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship Related TEAE	3 participants	3 participants	4 participants	3 participants
Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship Grade ≥3 TEAE	0 participants	2 participants	2 participants	1 participants
Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship Related Grade ≥3 TEAE	0 participants	0 participants	0 participants	1 participants
Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship Related serious TEAE	0 participants	1 participants	0 participants	1 participants
Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship TEAE of special interest	0 participants	1 participants	0 participants	0 participants
Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship TEAE leading to death	0 participants	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: From start of BNT141 treatment until the second Safety Follow-up Visit (60 ± 7 days after last dose), up to 30 weeks.

Population: Safety Set - All patients who received investigational medicinal product (IMP) (i.e., at least one dose of BNT141)

Outcome measures

Outcome measures
Measure	BNT141 Monotherapy - 0.15 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.15 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.30 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.30 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.45 mg/kg n=4 Participants The number of patients from Part 1A treated with BNT141 0.45 mg/kg, corresponding to an intermediate dose level. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.60 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.60 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.
Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs Related TEAE leading to dose rate reduction	0 participants	0 participants	0 participants	0 participants
Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs TEAE leading to treatment discontinuation	0 participants	0 participants	0 participants	0 participants
Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs Related TEAE leading to treatment discontinuation	0 participants	0 participants	0 participants	0 participants
Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs TEAE leading to study drug interruption	0 participants	2 participants	1 participants	1 participants
Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs Related TEAE leading to study drug interruption	0 participants	2 participants	0 participants	1 participants
Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs TEAE leading to dose reduction	0 participants	0 participants	0 participants	0 participants
Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs Related TEAE leading to dose reduction	0 participants	0 participants	0 participants	0 participants
Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs TEAE leading to dose rate reduction	0 participants	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: First treatment cycle (From first dose up to 21 days after first dose)

Population: Safety Set - All patients who received investigational medicinal product (IMP) (i.e., at least one dose of BNT141)

Serious AEs, non-serious Grade ≥ 3 non-hematological and hematological AEs as defined per DLT criteria and clinically significant abnormal laboratory values Grade ≥ 3 were collected and considered a DLT if assessed by the investigator to be at least possibly related to BNT141. Toxicities clearly not related to BNT141 (e.g., progressive disease, comorbidity, etc.) were not considered a DLT. The NCI CTCAE v.5.0 was used to grade the intensity of AEs.

Outcome measures

Outcome measures
Measure	BNT141 Monotherapy - 0.15 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.15 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.30 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.30 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.45 mg/kg n=4 Participants The number of patients from Part 1A treated with BNT141 0.45 mg/kg, corresponding to an intermediate dose level. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.60 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.60 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.
Occurrence of Dose-limiting Toxicities (DLTs) Within a Patient During the DLT Evaluation Period	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: First treatment cycle (From first dose up to 21 days after first dose)

Population: PK Set - All patients with baseline and at least one valid on-treatment/post-treatment PK assessment.

Intact RiboMab (full-length and fully assembled antibody) PK serum samples were collected and analyzed. AUC (0-tau), AUC (0-inf) and AUC (0-504) were estimated from serum concentration data from Cycle 1 using non-compartmental analysis. AUC (0-inf): Area under the drug concentration-time curve, from time zero to infinity. AUC (0-504): Area under the drug concentration-time curve, from time zero to 504 hours after the start of the infusion. AUC (0-tau): Area under the drug concentration-time curve, from time zero over the dosing interval at steady-state (Tau = 504 hours corresponding to 3-weeks administration) after the start of the infusion.

Outcome measures

Outcome measures
Measure	BNT141 Monotherapy - 0.15 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.15 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.30 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.30 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.45 mg/kg n=4 Participants The number of patients from Part 1A treated with BNT141 0.45 mg/kg, corresponding to an intermediate dose level. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.60 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.60 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.
RiboMab PK Parameter - Area Under the Concentration Time Curve (AUC) AUC (0-tau)	1613407.9486 h*ng/mL Geometric Coefficient of Variation 50	5798293.4278 h*ng/mL Geometric Coefficient of Variation 30	5499389.8684 h*ng/mL Geometric Coefficient of Variation 40	5244472.7649 h*ng/mL Geometric Coefficient of Variation 60
RiboMab PK Parameter - Area Under the Concentration Time Curve (AUC) AUC (0-inf)	2166227.7262 h*ng/mL Geometric Coefficient of Variation 50	9838894.4371 h*ng/mL Geometric Coefficient of Variation 50	9128700.3987 h*ng/mL Geometric Coefficient of Variation 50	6739801.3745 h*ng/mL Geometric Coefficient of Variation 50
RiboMab PK Parameter - Area Under the Concentration Time Curve (AUC) AUC (0-504)	1615489.8795 h*ng/mL Geometric Coefficient of Variation 50	5736526.2444 h*ng/mL Geometric Coefficient of Variation 30	6253473.9330 h*ng/mL Geometric Coefficient of Variation 40	5283854.6455 h*ng/mL Geometric Coefficient of Variation 60

SECONDARY outcome

Timeframe: First treatment cycle (From first dose up to 21 days after first dose)

Population: PK Set - All patients with baseline and at least one valid on-treatment/post-treatment PK assessment.

Intact RiboMab (full-length and fully assembled antibody) PK serum samples were collected and analyzed. Clearance was estimated from serum concentration from Cycle 1 data using non-compartmental analysis.

Outcome measures

Outcome measures
Measure	BNT141 Monotherapy - 0.15 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.15 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.30 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.30 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.45 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.45 mg/kg, corresponding to an intermediate dose level. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.60 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.60 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.
RiboMab PK Parameter - Clearance	0.0065 L/h Geometric Coefficient of Variation 60	0.0021 L/h Geometric Coefficient of Variation 40	0.0036 L/h Geometric Coefficient of Variation 50	0.0066 L/h Geometric Coefficient of Variation 70

SECONDARY outcome

Timeframe: First treatment cycle (From first dose up to 21 days after first dose)

Population: PK Set - All patients with baseline and at least one valid on-treatment/post-treatment PK assessment.

Intact RiboMab (full-length and fully assembled antibody) PK serum samples were collected and analyzed. Volume of distribution at steady state (Vss) was estimated as mean residence time calculated using last measured concentration (MRT inf) \* CL.

Outcome measures

Outcome measures
Measure	BNT141 Monotherapy - 0.15 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.15 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.30 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.30 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.45 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.45 mg/kg, corresponding to an intermediate dose level. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.60 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.60 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.
RiboMab PK Parameter - Volume of Distribution at Steady State (Vss)	2.2103 L Geometric Coefficient of Variation 70	1.1099 L Geometric Coefficient of Variation 40	1.5656 L Geometric Coefficient of Variation 20	2.0340 L Geometric Coefficient of Variation 80

SECONDARY outcome

Timeframe: First treatment cycle (From first dose up to 21 days after first dose)

Population: PK Set - All patients with baseline and at least one valid on-treatment/post-treatment PK assessment.

Intact RiboMab (full-length and fully assembled antibody) PK serum samples were collected and analyzed. Cmax was estimated from serum concentration from Cycle 1 data using non-compartmental analysis.

Outcome measures

Outcome measures
Measure	BNT141 Monotherapy - 0.15 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.15 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.30 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.30 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.45 mg/kg n=4 Participants The number of patients from Part 1A treated with BNT141 0.45 mg/kg, corresponding to an intermediate dose level. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.60 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.60 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.
RiboMab PK Parameter - Maximum Serum Drug Concentration (Cmax)	5844.7265 ng/mL Geometric Coefficient of Variation 60	17829.5955 ng/mL Geometric Coefficient of Variation 40	24001.7233 ng/mL Geometric Coefficient of Variation 40	19801.0462 ng/mL Geometric Coefficient of Variation 60

SECONDARY outcome

Timeframe: First treatment cycle (From first dose up to 21 days after first dose)

Population: PK Set - All patients with baseline and at least one valid on-treatment/post-treatment PK assessment.

Intact RiboMab (full-length and fully assembled antibody) PK serum samples were collected and analyzed. Tmax was estimated from serum concentration from Cycle 1 data using non-compartmental analysis.

Outcome measures

Outcome measures
Measure	BNT141 Monotherapy - 0.15 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.15 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.30 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.30 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.45 mg/kg n=4 Participants The number of patients from Part 1A treated with BNT141 0.45 mg/kg, corresponding to an intermediate dose level. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.60 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.60 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.
RiboMab PK Parameter - Time to Reach Cmax (Tmax)	59.80362 hours Geometric Coefficient of Variation 20	61.02810 hours Geometric Coefficient of Variation 20	68.18978 hours Geometric Coefficient of Variation 30	54.72251 hours Geometric Coefficient of Variation 20

SECONDARY outcome

Timeframe: Before start of Cycle 3 (plasma sample taken directly before BNT141 Cycle 3 administration)

Population: PK Set - All patients with baseline and at least one valid on-treatment/post-treatment PK assessment.

Intact RiboMab (full-length and fully assembled antibody) PK serum samples were collected and analyzed. Ctrough was estimated from serum concentration from Cycle 1 data using non-compartmental analysis. Ctrough values are available for participants treated with dose level 1 and dose level 2 only.

Outcome measures

Outcome measures
Measure	BNT141 Monotherapy - 0.15 mg/kg n=1 Participants The number of patients from Part 1A treated with BNT141 0.15 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.30 mg/kg n=2 Participants The number of patients from Part 1A treated with BNT141 0.30 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.45 mg/kg The number of patients from Part 1A treated with BNT141 0.45 mg/kg, corresponding to an intermediate dose level. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.60 mg/kg The number of patients from Part 1A treated with BNT141 0.60 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.
RiboMab PK Parameter - Concentration at the End of a Dosing Interval (Taken Directly Before Next Administration) (Ctrough)	3516.7500 ng/mL Geometric Coefficient of Variation NA Only data from one participant was analyzed.	3734.1225 ng/mL Geometric Coefficient of Variation 50	—	—

SECONDARY outcome

Timeframe: First treatment cycle (From first dose up to 21 days after first dose)

Population: PK Set - All patients with baseline and at least one valid on-treatment/post-treatment PK assessment.

Intact RiboMab (full-length and fully assembled antibody) PK serum samples were collected and analyzed. T½ was estimated from serum concentration from Cycle 1 data using non-compartmental analysis.

Outcome measures

Outcome measures
Measure	BNT141 Monotherapy - 0.15 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.15 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.30 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.30 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.45 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.45 mg/kg, corresponding to an intermediate dose level. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.60 mg/kg n=3 Participants The number of patients from Part 1A treated with BNT141 0.60 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.
RiboMab PK Parameter - Half-time (t½)	236.9571 hours Geometric Coefficient of Variation 10	366.7979 hours Geometric Coefficient of Variation 50	304.9024 hours Geometric Coefficient of Variation 30	214.7214 hours Geometric Coefficient of Variation 10

SECONDARY outcome

Timeframe: From start of first dose of BNT141 until end of trial or start of a new anti-cancer therapy, up to 30 weeks

Population: Data were not available for this endpoint due to early termination of the study meaning ORR could not be determined. Most participants were followed up for efficacy for a short period of time while on study (≤ 6 weeks), therefore there was insufficient follow-up for efficacy in most participants to conduct a meaningful assessment of ORR. As per statistical analysis plan, the analysis of secondary efficacy endpoint ORR was removed from the study analysis.

ORR was defined as the number of patients in whom a complete response (CR) or partial response (PR), per RECIST 1.1 is confirmed as best overall response.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From start of first dose of BNT141 until end of trial or start of a new anti-cancer therapy, up to 30 weeks

Population: Data were not available for this endpoint due to early termination of the study meaning DCR could not be determined. Most participants were followed up for efficacy for a short period of time while on study (≤ 6 weeks), therefore there was insufficient follow-up for efficacy in most participants to conduct a meaningful assessment of DCR. As per statistical analysis plan, the analysis of secondary efficacy endpoint DCR was removed from the study analysis.

DCR was defined as the number of patients in whom a CR or PR or stable disease (\[SD\], per RECIST 1.1, SD assessed at least 6 weeks after first dose) is observed as best overall response.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From start of first dose of BNT141 until end of trial or start of a new anti-cancer therapy, up to 30 weeks

Population: Data were not available for this endpoint due to early termination of the study meaning DoR could not be determined. Most participants were followed up for efficacy for a short period of time while on study (≤ 6 weeks), therefore there was insufficient follow-up for efficacy in most participants to conduct a meaningful assessment of DoR. As per statistical analysis plan, the analysis of secondary efficacy endpoint DoR was removed from the study analysis.

DOR was defined as the time from first objective response (CR or PR per RECIST 1.1) to first occurrence of objective tumor progression (progressive disease per RECIST 1.1) or death from any cause, whichever occurs first.

Outcome measures

Outcome data not reported

Adverse Events

BNT141 Monotherapy - 0.15 mg/kg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 1 deaths

BNT141 Monotherapy - 0.30 mg/kg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 1 deaths

BNT141 Monotherapy - 0.45 mg/kg

Serious events: 1 serious events

Other events: 4 other events

Deaths: 2 deaths

BNT141 Monotherapy - 0.60 mg/kg

Serious events: 2 serious events

Other events: 3 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	BNT141 Monotherapy - 0.15 mg/kg n=3 participants at risk The number of patients from Part 1A treated with BNT141 0.15 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.30 mg/kg n=3 participants at risk The number of patients from Part 1A treated with BNT141 0.30 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.45 mg/kg n=4 participants at risk The number of patients from Part 1A treated with BNT141 0.45 mg/kg, corresponding to an intermediate dose level. BNT141 was administered IV as monotherapy once every three weeks.	BNT141 Monotherapy - 0.60 mg/kg n=3 participants at risk The number of patients from Part 1A treated with BNT141 0.60 mg/kg. BNT141 was administered IV as monotherapy once every three weeks.
Immune system disorders Cytokine release syndrome	0.00% 0/3 • Deaths and SAEs: All events from the signing of the trial-specific informed consent from until the second Safety Follow-up Visit, up to 33 weeks. Other AEs: All TEAEs, i.e., AEs reported from the start of study drug treatment until the second Safety Follow-up Visit, up to 30 weeks. Other AEs: All TEAEs, i.e., AEs with an onset date on or after the first dose of BNT141 (if the AE was absent before the first dose) or worsened after the first dose of BNT141 (if the AE was present before the first dose). AEs with an onset date \>60 days after the last dose of BNT141 are included only if assessed as related to BNT141 by the investigator.	33.3% 1/3 • Deaths and SAEs: All events from the signing of the trial-specific informed consent from until the second Safety Follow-up Visit, up to 33 weeks. Other AEs: All TEAEs, i.e., AEs reported from the start of study drug treatment until the second Safety Follow-up Visit, up to 30 weeks. Other AEs: All TEAEs, i.e., AEs with an onset date on or after the first dose of BNT141 (if the AE was absent before the first dose) or worsened after the first dose of BNT141 (if the AE was present before the first dose). AEs with an onset date \>60 days after the last dose of BNT141 are included only if assessed as related to BNT141 by the investigator.	0.00% 0/4 • Deaths and SAEs: All events from the signing of the trial-specific informed consent from until the second Safety Follow-up Visit, up to 33 weeks. Other AEs: All TEAEs, i.e., AEs reported from the start of study drug treatment until the second Safety Follow-up Visit, up to 30 weeks. Other AEs: All TEAEs, i.e., AEs with an onset date on or after the first dose of BNT141 (if the AE was absent before the first dose) or worsened after the first dose of BNT141 (if the AE was present before the first dose). AEs with an onset date \>60 days after the last dose of BNT141 are included only if assessed as related to BNT141 by the investigator.	33.3% 1/3 • Deaths and SAEs: All events from the signing of the trial-specific informed consent from until the second Safety Follow-up Visit, up to 33 weeks. Other AEs: All TEAEs, i.e., AEs reported from the start of study drug treatment until the second Safety Follow-up Visit, up to 30 weeks. Other AEs: All TEAEs, i.e., AEs with an onset date on or after the first dose of BNT141 (if the AE was absent before the first dose) or worsened after the first dose of BNT141 (if the AE was present before the first dose). AEs with an onset date \>60 days after the last dose of BNT141 are included only if assessed as related to BNT141 by the investigator.
Infections and infestations Bacteraemia	33.3% 1/3 • Deaths and SAEs: All events from the signing of the trial-specific informed consent from until the second Safety Follow-up Visit, up to 33 weeks. Other AEs: All TEAEs, i.e., AEs reported from the start of study drug treatment until the second Safety Follow-up Visit, up to 30 weeks. Other AEs: All TEAEs, i.e., AEs with an onset date on or after the first dose of BNT141 (if the AE was absent before the first dose) or worsened after the first dose of BNT141 (if the AE was present before the first dose). AEs with an onset date \>60 days after the last dose of BNT141 are included only if assessed as related to BNT141 by the investigator.	0.00% 0/3 • Deaths and SAEs: All events from the signing of the trial-specific informed consent from until the second Safety Follow-up Visit, up to 33 weeks. Other AEs: All TEAEs, i.e., AEs reported from the start of study drug treatment until the second Safety Follow-up Visit, up to 30 weeks. Other AEs: All TEAEs, i.e., AEs with an onset date on or after the first dose of BNT141 (if the AE was absent before the first dose) or worsened after the first dose of BNT141 (if the AE was present before the first dose). AEs with an onset date \>60 days after the last dose of BNT141 are included only if assessed as related to BNT141 by the investigator.	0.00% 0/4 • Deaths and SAEs: All events from the signing of the trial-specific informed consent from until the second Safety Follow-up Visit, up to 33 weeks. Other AEs: All TEAEs, i.e., AEs reported from the start of study drug treatment until the second Safety Follow-up Visit, up to 30 weeks. Other AEs: All TEAEs, i.e., AEs with an onset date on or after the first dose of BNT141 (if the AE was absent before the first dose) or worsened after the first dose of BNT141 (if the AE was present before the first dose). AEs with an onset date \>60 days after the last dose of BNT141 are included only if assessed as related to BNT141 by the investigator.	0.00% 0/3 • Deaths and SAEs: All events from the signing of the trial-specific informed consent from until the second Safety Follow-up Visit, up to 33 weeks. Other AEs: All TEAEs, i.e., AEs reported from the start of study drug treatment until the second Safety Follow-up Visit, up to 30 weeks. Other AEs: All TEAEs, i.e., AEs with an onset date on or after the first dose of BNT141 (if the AE was absent before the first dose) or worsened after the first dose of BNT141 (if the AE was present before the first dose). AEs with an onset date \>60 days after the last dose of BNT141 are included only if assessed as related to BNT141 by the investigator.
Infections and infestations Enterococcal bacteraemia	0.00% 0/3 • Deaths and SAEs: All events from the signing of the trial-specific informed consent from until the second Safety Follow-up Visit, up to 33 weeks. Other AEs: All TEAEs, i.e., AEs reported from the start of study drug treatment until the second Safety Follow-up Visit, up to 30 weeks. Other AEs: All TEAEs, i.e., AEs with an onset date on or after the first dose of BNT141 (if the AE was absent before the first dose) or worsened after the first dose of BNT141 (if the AE was present before the first dose). AEs with an onset date \>60 days after the last dose of BNT141 are included only if assessed as related to BNT141 by the investigator.	0.00% 0/3 • Deaths and SAEs: All events from the signing of the trial-specific informed consent from until the second Safety Follow-up Visit, up to 33 weeks. Other AEs: All TEAEs, i.e., AEs reported from the start of study drug treatment until the second Safety Follow-up Visit, up to 30 weeks. Other AEs: All TEAEs, i.e., AEs with an onset date on or after the first dose of BNT141 (if the AE was absent before the first dose) or worsened after the first dose of BNT141 (if the AE was present before the first dose). AEs with an onset date \>60 days after the last dose of BNT141 are included only if assessed as related to BNT141 by the investigator.	25.0% 1/4 • Deaths and SAEs: All events from the signing of the trial-specific informed consent from until the second Safety Follow-up Visit, up to 33 weeks. Other AEs: All TEAEs, i.e., AEs reported from the start of study drug treatment until the second Safety Follow-up Visit, up to 30 weeks. Other AEs: All TEAEs, i.e., AEs with an onset date on or after the first dose of BNT141 (if the AE was absent before the first dose) or worsened after the first dose of BNT141 (if the AE was present before the first dose). AEs with an onset date \>60 days after the last dose of BNT141 are included only if assessed as related to BNT141 by the investigator.	0.00% 0/3 • Deaths and SAEs: All events from the signing of the trial-specific informed consent from until the second Safety Follow-up Visit, up to 33 weeks. Other AEs: All TEAEs, i.e., AEs reported from the start of study drug treatment until the second Safety Follow-up Visit, up to 30 weeks. Other AEs: All TEAEs, i.e., AEs with an onset date on or after the first dose of BNT141 (if the AE was absent before the first dose) or worsened after the first dose of BNT141 (if the AE was present before the first dose). AEs with an onset date \>60 days after the last dose of BNT141 are included only if assessed as related to BNT141 by the investigator.
Vascular disorders Embolism	0.00% 0/3 • Deaths and SAEs: All events from the signing of the trial-specific informed consent from until the second Safety Follow-up Visit, up to 33 weeks. Other AEs: All TEAEs, i.e., AEs reported from the start of study drug treatment until the second Safety Follow-up Visit, up to 30 weeks. Other AEs: All TEAEs, i.e., AEs with an onset date on or after the first dose of BNT141 (if the AE was absent before the first dose) or worsened after the first dose of BNT141 (if the AE was present before the first dose). AEs with an onset date \>60 days after the last dose of BNT141 are included only if assessed as related to BNT141 by the investigator.	0.00% 0/3 • Deaths and SAEs: All events from the signing of the trial-specific informed consent from until the second Safety Follow-up Visit, up to 33 weeks. Other AEs: All TEAEs, i.e., AEs reported from the start of study drug treatment until the second Safety Follow-up Visit, up to 30 weeks. Other AEs: All TEAEs, i.e., AEs with an onset date on or after the first dose of BNT141 (if the AE was absent before the first dose) or worsened after the first dose of BNT141 (if the AE was present before the first dose). AEs with an onset date \>60 days after the last dose of BNT141 are included only if assessed as related to BNT141 by the investigator.	0.00% 0/4 • Deaths and SAEs: All events from the signing of the trial-specific informed consent from until the second Safety Follow-up Visit, up to 33 weeks. Other AEs: All TEAEs, i.e., AEs reported from the start of study drug treatment until the second Safety Follow-up Visit, up to 30 weeks. Other AEs: All TEAEs, i.e., AEs with an onset date on or after the first dose of BNT141 (if the AE was absent before the first dose) or worsened after the first dose of BNT141 (if the AE was present before the first dose). AEs with an onset date \>60 days after the last dose of BNT141 are included only if assessed as related to BNT141 by the investigator.	33.3% 1/3 • Deaths and SAEs: All events from the signing of the trial-specific informed consent from until the second Safety Follow-up Visit, up to 33 weeks. Other AEs: All TEAEs, i.e., AEs reported from the start of study drug treatment until the second Safety Follow-up Visit, up to 30 weeks. Other AEs: All TEAEs, i.e., AEs with an onset date on or after the first dose of BNT141 (if the AE was absent before the first dose) or worsened after the first dose of BNT141 (if the AE was present before the first dose). AEs with an onset date \>60 days after the last dose of BNT141 are included only if assessed as related to BNT141 by the investigator.

Other adverse events

Additional Information

BioNTech clinical trials patient information

BioNTech SE

Phone: +49 6131 9084

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee There IS an agreement between the Principal Investigator and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. Principal Investigators respectively trial sites shall not publish or refer to in writing or orally, in whole or in part, any data, information or materials generated from the study and the services, without the prior written consent of the sponsor.
Publication restrictions are in place

Restriction type: OTHER