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

Phase I/IIa, First-in-human, Open-label, Dose Escalation Trial With Expansion Cohorts to Evaluate Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of BNT141 as a Monotherapy and in Combination With Other Anti-cancer Agents in Patients With CLDN18.2-positive Solid Tumors

Status

Terminated

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04683939

Enrollment

Registered

2020-12-24

Start date

2022-01-18

Completion date

2023-07-24

Last updated

2024-10-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Biliary Tract Cancer, Cholangiocarcinoma, Esophageal Adenocarcinoma, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, Metastatic Cancer, Pancreatic Cancer, Solid Tumor

Keywords

CLDN18.2-positive solid tumors, Gastric cancer, Gastric adenocarcinoma, Gastroesophageal junction adenocarcinoma, Esophageal adenocarcinoma, Esophageal cancer, Pancreatic cancer, Pancreatic ductal adenocarcinoma, Biliary tract cancers, Cholangiocarcinoma, Mucinous ovarian cancers, Metastatic, Treatment, Therapy, Targeted immunotherapy, Metastatic cancer, Ribomab, CLDN18.2-positive tumors, Biomarker, Precision medicine, Precision oncology, Solid tumors, mRNA

Brief summary

This study was planned as an open-label, multi-site, Phase I/IIa dose escalation, safety, and pharmacokinetic (PK) trial of BNT141 followed by expansion cohorts in patients with Claudin 18.2 (CLDN18.2)-positive tumors. The sponsor decided to stop the development of BNT141 on 24 July 2023 and the study was terminated early.

Detailed description

The study design consisted of three parts: * Part 1A was a dose escalation of BNT141 as monotherapy in patients with advanced unresectable or metastatic CLDN18.2-positive solid tumors for which there was no available standard therapy considered to confer clinical benefit, or the patient was not a candidate for such available therapy. The dose of BNT141 was planned to be escalated until the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of BNT141 as monotherapy was defined. However, due to the early study termination, the dose of BNT141 was not fully escalated as planned per protocol (i.e., only four doses were tested, i.e., 0.15 mg/kg, 0.30 mg/kg, 0.45 mg/kg, and 0.60 mg/kg). Once the MTD was reached, up to 10 additional patients with CLDN18.2 expressing pancreatic and biliary tract cancers were planned to be enrolled at the MTD level to obtain additional data on safety, PK and pharmacodynamics (PD). Eligible tumor types were gastric cancer, gastroesophageal junction (GEJ) and esophageal adenocarcinoma, pancreatic, biliary tract (cholangiocarcinoma and gallbladder cancer), and mucinous ovarian cancers. Additionally, patients with specific tumors (including colorectal cancer, non-small-cell lung cancer, gastric subtype of endocervical adenocarcinoma) where there is scientific evidence that the CLDN18.2 could be elevated could be tested for CLDN18.2 expression. * Part 1B was planned to be a dose escalation of BNT141 in combination with nab-paclitaxel and gemcitabine in patients with locally advanced unresectable or metastatic CLDN18.2-positive pancreatic adenocarcinoma or cholangiocarcinoma who were eligible for treatment with nab-paclitaxel and gemcitabine. Part 1B intended to define the MTD and/or RP2D of the combination. Once the MTD was reached, up to 10 additional patients with CLDN18.2-expressing pancreatic adenocarcinoma or cholangiocarcinoma were planned to be enrolled at the MTD level to obtain additional data on safety, PK and PD. The MTD of BNT141 in combination with nab-paclitaxel and gemcitabine in Part 1B was planned to not exceed the monotherapy BNT141 MTD determined in Part 1A. * Part 2 (Expansion) was planned to consist of two predefined expansion cohorts in patients with CLDN18.2-positive solid tumors eligible for treatment with nab-paclitaxel and gemcitabine. Part 1B and Part 2 did not proceed and no participant was enrolled in Part 1B and Part 2.

Interventions

DRUGBNT141

Intravenous (IV)

DRUGNab-paclitaxel

DRUGGemcitabine

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

Inclusion criteria

Key inclusion criteria: For all Parts: * Metastatic or unresectable solid tumor. * Histological or cytological documentation of a solid tumor via a pathology report. * CLDN18.2-positive tumor sample defined as moderate-to-strong CLDN18.2 protein expression defined as intermediate (2+) to strong (3+) staining intensity in ≥ 50% of tumor cells as assessed by central testing using a CLIA-validated immunohistochemistry assay in formalin-fixed, paraffin-embedded (FFPE) neoplastic tissues. New biopsies and archival bio-samples are allowed. Bone biopsies are not allowed. Cytology specimens (including fine needle aspirates) will not be accepted for CLDN18.2 examination. If archival tissue samples from several points of time are available, the most recent one is preferred. Patients with a lower expression level or with CLDN18.2-negative cancers are not eligible. Trial part-specific inclusion criteria: For Part 1A: Patients with solid tumors, for which there is no available standard therapy likely to confer clinical benefit, or the patient is not a candidate for such available therapy. Patients must have received all available standard therapies and failed at least first-line standard of care therapy prior to enrolment. Measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Eligible tumor types are gastric cancer, GEJ and esophageal adenocarcinoma, pancreatic, biliary tract (cholangiocarcinoma and gallbladder cancer), and mucinous ovarian cancers. Additionally, patients with specific tumors (including colorectal cancer, non small-cell lung cancer, gastric subtype of endocervical adenocarcinoma) where there is scientific evidence that the CLDN18.2 could be elevated can be tested for CLDN18.2 expression. For Part 1B: Patients with advanced pancreatic adenocarcinoma or cholangiocarcinoma who are eligible for treatment with nab-paclitaxel and gemcitabine. Measurable or evaluable disease per RECIST 1.1. Key

Exclusion criteria

* Receiving: radiotherapy, chemotherapy, or molecularly-targeted agents within 3 weeks or 5 half-lives (whichever is longer) of the start of trial treatment; immunotherapy/monoclonal antibodies within 3 weeks of the start of trial treatment (excluding BNT141); nitrosoureas, antibody-drug conjugates, or radioactive isotopes within 6 weeks of the start of trial treatment. Palliative radiotherapy will be allowed. * Receives concurrent systemic (oral or IV) steroid therapy \>10 mg prednisone daily or its equivalent for an underlying condition. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is permitted. * Major surgery within 4 weeks before the first dose of BNT141. * Prior treatment with a CLDN18.2 targeting monoclonal antibodies (mAb) other than BNT141. * Ongoing or active infection requiring IV treatment with anti-infective therapy that has been administered less than 2 weeks prior to the first dose of BNT141. * 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.5.0 Grade ≤ 1, with the exception of anorexia, fatigue, hyperthyroidism, hypothyroidism, and peripheral neuropathy, which must have recovered to ≤ Grade 2. Alopecia of any grade is allowed. * Current evidence of new or growing brain or leptomeningeal metastases during screening. Patients with known brain or leptomeningeal metastases may be eligible if they have: * Radiotherapy, surgery or stereotactic surgery for the brain or leptomeningeal metastases. * No neurological symptoms (excluding Grade ≤ 2 neuropathy). * Stable brain or leptomeningeal disease on the computer tomography or magnet resonance imaging scan within 4 weeks before signing the informed consent form. * Not undergoing acute corticosteroid therapy or steroid taper. Additional inclusion and

Design outcomes

Primary

Measure	Time frame	Description
Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	From start of BNT141 treatment until the second Safety Follow-up Visit (60 ± 7 days after last dose), up to 30 weeks.	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
Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	From start of BNT141 treatment until the second Safety Follow-up Visit (60 ± 7 days after last dose), up to 30 weeks.	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
Occurrence of Dose-limiting Toxicities (DLTs) Within a Patient During the DLT Evaluation Period	First treatment cycle (From first dose up to 21 days after first dose)	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.

Secondary

Measure	Time frame	Description
RiboMab PK Parameter - Maximum Serum Drug Concentration (Cmax)	First treatment cycle (From first dose up to 21 days after first dose)	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.
RiboMab PK Parameter - Time to Reach Cmax (Tmax)	First treatment cycle (From first dose up to 21 days after first dose)	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.
RiboMab PK Parameter - Concentration at the End of a Dosing Interval (Taken Directly Before Next Administration) (Ctrough)	Before start of Cycle 3 (plasma sample taken directly before BNT141 Cycle 3 administration)	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.
RiboMab PK Parameter - Area Under the Concentration Time Curve (AUC)	First treatment cycle (From first dose up to 21 days after first dose)	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.
Objective Response Rate (ORR)	From start of first dose of BNT141 until end of trial or start of a new anti-cancer therapy, up to 30 weeks	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.
Disease Control Rate (DCR)	From start of first dose of BNT141 until end of trial or start of a new anti-cancer therapy, up to 30 weeks	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.
Duration of Response (DoR)	From start of first dose of BNT141 until end of trial or start of a new anti-cancer therapy, up to 30 weeks	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.
RiboMab PK Parameter - Half-time (t½)	First treatment cycle (From first dose up to 21 days after first dose)	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.
RiboMab PK Parameter - Clearance	First treatment cycle (From first dose up to 21 days after first dose)	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.
RiboMab PK Parameter - Volume of Distribution at Steady State (Vss)	First treatment cycle (From first dose up to 21 days after first dose)	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.

Countries

Canada, United States

Participant flow

Recruitment details

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.

Pre-assignment details

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.

Participants by arm

Arm	Count
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.	3
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.	3
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.	4
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.	3
Total	13

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Death	1	1	2	1
Overall Study	Lost to Follow-up	0	1	0	0
Overall Study	Physician Decision	1	0	0	0
Overall Study	Study termination by the sponsor	0	1	2	2
Overall Study	Withdrawal by Subject	1	0	0	0

Baseline characteristics

Characteristic	BNT141 Monotherapy - 0.15 mg/kg	Total	BNT141 Monotherapy - 0.60 mg/kg	BNT141 Monotherapy - 0.45 mg/kg	BNT141 Monotherapy - 0.30 mg/kg
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	1 Participants	9 Participants	3 Participants	2 Participants	3 Participants
Age, Categorical Between 18 and 65 years	2 Participants	4 Participants	0 Participants	2 Participants	0 Participants
Age, Continuous	56.0 years STANDARD_DEVIATION 15.52	64.9 years STANDARD_DEVIATION 12.71	74.0 years STANDARD_DEVIATION 6.24	58.3 years STANDARD_DEVIATION 11.35	73.7 years STANDARD_DEVIATION 7.02
Body Mass Index (BMI)	32.56 kg/m^2 STANDARD_DEVIATION 7.12	25.14 kg/m^2 STANDARD_DEVIATION 6.42	24.67 kg/m^2 STANDARD_DEVIATION 5.53	20.46 kg/m^2 STANDARD_DEVIATION 4.888	24.41 kg/m^2 STANDARD_DEVIATION 1.541
Eastern Cooperative Oncology Group performance score (ECOG PS) ECOG PS 0	0 Participants	4 Participants	0 Participants	2 Participants	2 Participants
Eastern Cooperative Oncology Group performance score (ECOG PS) ECOG PS 1	3 Participants	9 Participants	3 Participants	2 Participants	1 Participants
Eastern Cooperative Oncology Group performance score (ECOG PS) ECOG PS 2	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of prior systemic cancer therapies per patient	3.7 number of therapies STANDARD_DEVIATION 1.15	3.2 number of therapies STANDARD_DEVIATION 1.46	1.7 number of therapies STANDARD_DEVIATION 0.58	3.8 number of therapies STANDARD_DEVIATION 0.5	3.3 number of therapies STANDARD_DEVIATION 2.52
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	2 Participants	12 Participants	3 Participants	4 Participants	3 Participants
Region of Enrollment Canada	0 participants	5 participants	2 participants	2 participants	1 participants
Region of Enrollment United States	3 participants	8 participants	1 participants	2 participants	2 participants
Sex: Female, Male Female	1 Participants	3 Participants	0 Participants	1 Participants	1 Participants
Sex: Female, Male Male	2 Participants	10 Participants	3 Participants	3 Participants	2 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	1 / 3	1 / 3	2 / 4	1 / 3
other Total, other adverse events	3 / 3	3 / 3	4 / 4	3 / 3
serious Total, serious adverse events	1 / 3	1 / 3	1 / 4	2 / 3

Outcome results

Primary

Occurrence of Dose-limiting Toxicities (DLTs) Within a Patient During the DLT Evaluation Period

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.

Time frame: 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)

Arm	Measure	Value (NUMBER)
BNT141 Monotherapy - 0.15 mg/kg	Occurrence of Dose-limiting Toxicities (DLTs) Within a Patient During the DLT Evaluation Period	0 participants
BNT141 Monotherapy - 0.30 mg/kg	Occurrence of Dose-limiting Toxicities (DLTs) Within a Patient During the DLT Evaluation Period	0 participants
BNT141 Monotherapy - 0.45 mg/kg	Occurrence of Dose-limiting Toxicities (DLTs) Within a Patient During the DLT Evaluation Period	0 participants
BNT141 Monotherapy - 0.60 mg/kg	Occurrence of Dose-limiting Toxicities (DLTs) Within a Patient During the DLT Evaluation Period	0 participants

Primary

Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs

Time frame: 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)

Arm	Measure	Group	Value (NUMBER)
BNT141 Monotherapy - 0.15 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	TEAE leading to dose reduction	0 participants
BNT141 Monotherapy - 0.15 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	Related TEAE leading to dose reduction	0 participants
BNT141 Monotherapy - 0.15 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	Related TEAE leading to dose rate reduction	0 participants
BNT141 Monotherapy - 0.15 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	TEAE leading to study drug interruption	0 participants
BNT141 Monotherapy - 0.15 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	TEAE leading to treatment discontinuation	0 participants
BNT141 Monotherapy - 0.15 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	TEAE leading to dose rate reduction	0 participants
BNT141 Monotherapy - 0.15 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	Related TEAE leading to study drug interruption	0 participants
BNT141 Monotherapy - 0.15 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	Related TEAE leading to treatment discontinuation	0 participants
BNT141 Monotherapy - 0.30 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	Related TEAE leading to study drug interruption	2 participants
BNT141 Monotherapy - 0.30 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	Related TEAE leading to dose reduction	0 participants
BNT141 Monotherapy - 0.30 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	TEAE leading to dose reduction	0 participants
BNT141 Monotherapy - 0.30 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	Related TEAE leading to dose rate reduction	0 participants
BNT141 Monotherapy - 0.30 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	Related TEAE leading to treatment discontinuation	0 participants
BNT141 Monotherapy - 0.30 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	TEAE leading to study drug interruption	2 participants
BNT141 Monotherapy - 0.30 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	TEAE leading to dose rate reduction	0 participants
BNT141 Monotherapy - 0.30 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	TEAE leading to treatment discontinuation	0 participants
BNT141 Monotherapy - 0.45 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	Related TEAE leading to study drug interruption	0 participants
BNT141 Monotherapy - 0.45 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	TEAE leading to treatment discontinuation	0 participants
BNT141 Monotherapy - 0.45 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	Related TEAE leading to treatment discontinuation	0 participants
BNT141 Monotherapy - 0.45 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	TEAE leading to study drug interruption	1 participants
BNT141 Monotherapy - 0.45 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	Related TEAE leading to dose rate reduction	0 participants
BNT141 Monotherapy - 0.45 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	TEAE leading to dose reduction	0 participants
BNT141 Monotherapy - 0.45 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	Related TEAE leading to dose reduction	0 participants
BNT141 Monotherapy - 0.45 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	TEAE leading to dose rate reduction	0 participants
BNT141 Monotherapy - 0.60 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	TEAE leading to treatment discontinuation	0 participants
BNT141 Monotherapy - 0.60 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	Related TEAE leading to dose reduction	0 participants
BNT141 Monotherapy - 0.60 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	TEAE leading to study drug interruption	1 participants
BNT141 Monotherapy - 0.60 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	Related TEAE leading to treatment discontinuation	0 participants
BNT141 Monotherapy - 0.60 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	Related TEAE leading to dose rate reduction	0 participants
BNT141 Monotherapy - 0.60 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	TEAE leading to dose rate reduction	0 participants
BNT141 Monotherapy - 0.60 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	TEAE leading to dose reduction	0 participants
BNT141 Monotherapy - 0.60 mg/kg	Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs	Related TEAE leading to study drug interruption	1 participants

Primary

Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship

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

Time frame: 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)

Arm	Measure	Group	Value (NUMBER)
BNT141 Monotherapy - 0.15 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	Any TEAE	3 participants
BNT141 Monotherapy - 0.15 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	Related TEAE	3 participants
BNT141 Monotherapy - 0.15 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	Grade ≥3 TEAE	0 participants
BNT141 Monotherapy - 0.15 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	Related Grade ≥3 TEAE	0 participants
BNT141 Monotherapy - 0.15 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	Any serious TEAE	1 participants
BNT141 Monotherapy - 0.15 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	Related serious TEAE	0 participants
BNT141 Monotherapy - 0.15 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	TEAE of special interest	0 participants
BNT141 Monotherapy - 0.15 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	TEAE leading to death	0 participants
BNT141 Monotherapy - 0.30 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	Related serious TEAE	1 participants
BNT141 Monotherapy - 0.30 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	Any serious TEAE	1 participants
BNT141 Monotherapy - 0.30 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	Related TEAE	3 participants
BNT141 Monotherapy - 0.30 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	TEAE leading to death	0 participants
BNT141 Monotherapy - 0.30 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	TEAE of special interest	1 participants
BNT141 Monotherapy - 0.30 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	Related Grade ≥3 TEAE	0 participants
BNT141 Monotherapy - 0.30 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	Grade ≥3 TEAE	2 participants
BNT141 Monotherapy - 0.30 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	Any TEAE	3 participants
BNT141 Monotherapy - 0.45 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	TEAE of special interest	0 participants
BNT141 Monotherapy - 0.45 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	Grade ≥3 TEAE	2 participants
BNT141 Monotherapy - 0.45 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	Related Grade ≥3 TEAE	0 participants
BNT141 Monotherapy - 0.45 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	Any serious TEAE	1 participants
BNT141 Monotherapy - 0.45 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	Related serious TEAE	0 participants
BNT141 Monotherapy - 0.45 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	TEAE leading to death	0 participants
BNT141 Monotherapy - 0.45 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	Any TEAE	4 participants
BNT141 Monotherapy - 0.45 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	Related TEAE	4 participants
BNT141 Monotherapy - 0.60 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	Grade ≥3 TEAE	1 participants
BNT141 Monotherapy - 0.60 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	Related Grade ≥3 TEAE	1 participants
BNT141 Monotherapy - 0.60 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	Related TEAE	3 participants
BNT141 Monotherapy - 0.60 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	Any TEAE	3 participants
BNT141 Monotherapy - 0.60 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	Any serious TEAE	2 participants
BNT141 Monotherapy - 0.60 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	TEAE leading to death	0 participants
BNT141 Monotherapy - 0.60 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	TEAE of special interest	0 participants
BNT141 Monotherapy - 0.60 mg/kg	Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship	Related serious TEAE	1 participants

Secondary

Disease Control Rate (DCR)

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.

Time frame: 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.

Secondary

Duration of Response (DoR)

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.

Time frame: 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.

Secondary

Objective Response Rate (ORR)

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.

Time frame: 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.

Secondary

RiboMab PK Parameter - Area Under the Concentration Time Curve (AUC)

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.

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