PUMITAMIG for Advanced solid tumors

Inclusion criteria

• {"criterion_text":"- Participants need to be able to give informed consent and have given written consent in accordance with International Conference on Harmonisation Good Clinical Practice (ICH GCP) and local legislation prior to the start of any trial-specific procedures.\n- For Part 2 only: Qualitative urine protein ≤1+. If qualitative urine protein is ≥2+, a 24 h urine protein quantitative test is required. If the 24 h urine protein result is <1 g, participants can be enrolled.\n- Agree not to enroll in another clinical trial of an investigational medicinal product (IMP), starting at the time of giving informed consent and continuously until the last planned visit in this trial.\n- People of child-bearing potential (POCBP) who have a negative serum β-hCG pregnancy test, agree to practice a highly effective form of contraception, require their potentially fertile male partners to use condoms, and agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the trial.\n- Men who are sterile, or if they are potentially fertile and sexually active with a partner of child-bearing potential, agree to use condoms and to ask their sexual partners to practice a highly effective form of contraception during the trial, and are willing to refrain from sperm donation.\n- Fulfil the cohort-specific inclusion criteria as detailed in the trial protocol.\n- Participants are willing and able to comply with scheduled visits, treatment schedule, the planned trial assessments, lifestyle restrictions, and other requirements of the trial. This includes that they can understand and follow trial-related instructions.\n- Participants must be 18 years of age or older at the time of giving informed consent. Local laws will be followed if the age of consent is older.\n- Have histologic or cytologic documented advanced disease, either at relapse or upon diagnosis of metastatic disease.\n- Have measurable disease defined by RECIST 1.1.\n- All participants must provide a tumor tissue sample (FFPE slides) from archival tissue. The archival tissue can be an FFPE block or freshly cut slides derived from the advanced setting. If archival tissue is not available, a fresh biopsy must be collected, collection must be before Cycle 1 Day 1. Details are provided in the Laboratory Manual. If a tumor tissue sample cannot be provided, enrollment depends on approval by the sponsor’s medical monitor.\n- Have ECOG performance status of 0 or 1.\n- Have adequate organ and bone marrow function within 7 days before randomization/enrollment.\n- Have had an adequate washout period of previous treatments before randomization/enrolment."}

Exclusion criteria

• {"criterion_text":"- Prior treatment with an agent targeting HER3 (including antibody, antibody-drug conjugates (ADCs), cell therapy, and other drugs).\n- Have a history of Grade 3 or higher immune-related adverse events (irAEs) that led to treatment discontinuation of a prior checkpoint inhibitor.\n- Have active or a history of autoimmune disease with a risk of exacerbation following PD-L1 inhibition or have an immune deficiency.\n- Have received any IMP within 28 days or five half-lives if known (whichever is longer) before administration of first dose of IMP or are participating in the active treatment period of another interventional clinical trial.\n- Have serious non-healing wounds, ulcers, or bone fractures.\n- Have hypertension or diabetic conditions prior to trial treatment including people with a history of hypertensive crisis or hypertensive encephalopathy.\n- Have a history of significant hematologic toxicity to prior lines of therapy, as assessed by investigator.\n- Have an uncontrolled concomitant or intercurrent illness, that contra-indicates trial participation, limits compliance with trial procedures or substantially increases the risk of incurring adverse events (AEs).\n- Have active or have a history of uncontrolled or significant cardiovascular disease.\n- Have left ventricular ejection fraction (LVEF) below 50% by either ECHO or MUGA within 28 days before randomization/enrollment.\n- Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization / enrollment.\n- Have active or chronic corneal disorders or any clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy.\n- Have a history of (non-infectious) interstitial lung disease (ILD) / pneumonitis that required steroids, have current ILD / pneumonitis, or where suspected ILD / pneumonitis cannot be ruled out by imaging at screening.\n- Have a history of another primary malignancy within 2 years or have a known additional malignancy that is progressing or requires treatment.\n- Have a medical, psychological, or social condition or substance abuse 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.\n- Have a history of any of prior immunosuppressive medication within 14 days prior to first dose of IMP or prior live-attenuated vaccine within 30 days prior to the first dose of IMP, or prior randomization or treatment in a previous trial with the same IMPs as the current trial, regardless of treatment assignment.\n- Are subject to exclusion periods from another investigational trial.\n- Are vulnerable individuals as per ICH E6 definition, i.e. are individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.\n- Are fulfilling any of the cohort-specific exclusion criteria as detailed in the trial protocol.\n- Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.\n- Have clinically active central nervous system metastases.\n- Participants with significant risks of hemorrhage or evidence of major coagulation disorders.\n- Are a candidate to locoregional treatment (including surgical resection, stereotactic radiation therapy or tumor ablation) with potential to induce complete or near complete response and prolonged tumor control, per investigator’s assessment.\n- Have a history of intolerance to treatment with an anti-VEFG, anti-PD-1/PDL-1, or similar substance, including, but not limited to, bevacizumab, ramucirumab, atezolizumab, pembrolizumab, nivolumab, or other related therapies.\n- Have a known history or a positive test at screening of HIV 1 or 2 infection or hepatitis B infection. Participants with a negative hepatitis C virus (HCV)-antibody test at screening or positive HCV antibody test followed by a negative HCV RNA test at screening are eligible.\n- Have unresolved toxicities from previous anti-cancer therapy, defined as toxicities (other than alopecia) not yet resolved to at or below Grade 1 or baseline.\n- Are POCBP who are pregnant or breastfeeding or are planning pregnancy or potentially fertile males, who are planning to father children.\n- Have a history of allergies, hypersensitivities, or intolerance to the trial treatments including any excipients thereof.\n- Have a history of intolerance to treatment with a topoisomerase I inhibitor or intolerance to an ADC that consists of a topoisomerase I inhibitor, including but not limited to topotecan, irinotecan, and deruxtecan (DXd) (e.g., severe diarrhea).\n- Have 24-h urine protein excretion of 1 g or more."}

Primary endpoints

• {"endpoint_text":"- For Part I (monotherapy): Occurrence of treatment-emergent adverse events (TEAEs), treatment-emergent related adverse events (TRAEs), treatment-emergent serious adverse events (TESAEs), and treatment-emergent related serious adverse events (TRSAEs), by cohort and dose, from the time of initiation of the first dose of IMP to 42 days after the last dose of IMP or until a new anti-cancer therapy is started.","definition_or_measurement_approach":"Occurrence of TEAEs/TRAEs/TESAEs/TRSAEs recorded by cohort and dose from first IMP dose to 42 days after last dose or until new anti-cancer therapy is started (safety monitoring)."}
• {"endpoint_text":"- For Part I (monotherapy): Occurrence of dose interruption, reduction, and treatment discontinuations due to TEAEs, by cohort and dose, from the time of initiation of the first dose of IMP to 42 days after the last dose of IMP or until a new systemic anti-cancer therapy is started, whichever occurs first.","definition_or_measurement_approach":"Incidence of dose interruptions, reductions and discontinuations due to TEAEs by cohort and dose during same safety window (first dose to 42 days after last dose or until new systemic therapy)."}
• {"endpoint_text":"- For Part I (monotherapy): Confirmed objective response rate (ORR), defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) based on the investigator’s assessment (per RECIST 1.1) is observed as best overall response, by cohort and dose.","definition_or_measurement_approach":"ORR = proportion with confirmed CR or PR per investigator assessment using RECIST 1.1 as best overall response, reported by cohort and dose."}
• {"endpoint_text":"- Part 2 (combination therapy): Occurrence of treatment-emergent adverse events (TEAEs), treatment-emergent related adverse events (TRAEs), treatment-emergent serious adverse events (TESAEs), and treatment-emergent serious related adverse events (TRSAEs), and dose interruption, reduction, and discontinuation due to TEAEs, by cohort and dose.","definition_or_measurement_approach":"Occurrence of TEAEs/TRAEs/TESAEs/TRSAEs and dose modifications due to TEAEs by cohort and dose (safety monitoring during combination therapy)."}
• {"endpoint_text":"- Part 2 (combination therapy): Occurrence of dose-limiting toxicities (DLTs) during the DLT observation period.","definition_or_measurement_approach":"Incidence of DLTs observed during the predefined DLT observation period (used for dose-escalation decisions)."}
• {"endpoint_text":"- Part 2 (combination therapy): Confirmed objective response rate (ORR), defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) per RECIST 1.1 based on the investigator’s assessment, is observed as best overall response, by cohort and combination treatment regimen.","definition_or_measurement_approach":"ORR = proportion with confirmed CR or PR per RECIST 1.1 by investigator assessment, reported by cohort and combination regimen."}

Secondary endpoints

• {"endpoint_text":"- Parts 1 and 2: Progression-free survival (PFS), based on the investigator’s assessment, defined as the time from first dose of IMP to the first objective tumor progression (progressive disease (PD) per RECIST 1.1) or death from any cause, whichever occurs first, by cohort and combination treatment regimen.","definition_or_measurement_approach":"PFS = time from first IMP dose to first objective tumor progression (PD per RECIST 1.1 by investigator) or death from any cause, by cohort and regimen."}
• {"endpoint_text":"- Parts 1 and 2: Depth of response (DpR) defined as the maximum percent reduction from baseline in tumor size measured by sum of target lesion diameter, by cohort and combination treatment regimen.","definition_or_measurement_approach":"DpR = maximum percent reduction from baseline in sum of target lesion diameters, by cohort and regimen."}
• {"endpoint_text":"- Parts 1 and 2: Disease control rate (DCR) defined as the proportion of participants with a confirmed complete response (CR), partial response (PR), or a stable disease (per RECIST 1.1 based on the investigator’s assessment) as best overall response, by cohort and combination treatment regimen.","definition_or_measurement_approach":"DCR = proportion with confirmed CR, PR or stable disease per RECIST 1.1 by investigator as best overall response, by cohort and regimen."}
• {"endpoint_text":"- Parts 1 and 2: Duration of response (DOR) defined as the time from first objective response (CR or PR per RECIST 1.1 based on the investigator’s assessment) to first occurrence of objective tumor progression (PD per RECIST 1.1 based on the investigator’s assessment) or death from any cause, whichever occurs first, by cohort and combination treatment regimen.","definition_or_measurement_approach":"DOR = time from first objective response (CR or PR per RECIST 1.1) to first objective tumor progression or death, by cohort and regimen."}
• {"endpoint_text":"- Parts 1 and 2: Time to response (TTR) defined as the time from first dose of IMP to first objective response (CR or PR per RECIST 1.1 based on the investigator’s assessment), by cohort and combination treatment regimen.","definition_or_measurement_approach":"TTR = time from first IMP dose to first objective response (CR or PR per RECIST 1.1), by cohort and regimen."}
• {"endpoint_text":"- Parts 1 and 2: Overall survival (OS) defined as the time from first dose of IMP to death from any cause, by cohort and combination treatment regimen.","definition_or_measurement_approach":"OS = time from first IMP dose to death from any cause, by cohort and regimen."}
• {"endpoint_text":"- Parts 1 and 2: Pharmacokinetic (PK) parameters derived from serum concentrations of BNT326 ADC, total anti-HER3 antibody component, and unconjugated payload YL0010014 component, by cohort and combination treatment regimen.","definition_or_measurement_approach":"PK parameters derived from serum concentrations of BNT326 ADC, total anti-HER3 antibody component and unconjugated payload YL0010014, analyzed by cohort and regimen."}
• {"endpoint_text":"- Parts 1 and 2: Anti-drug antibody (ADA) prevalence and ADA incidence up to 1 year from the last dose of IMP, by cohort and combination treatment regimen.","definition_or_measurement_approach":"ADA prevalence and incidence measured up to 1 year after last IMP dose, by cohort and regimen."}

Methods

• Doctor-to-Patient Letter (K2 documents) distributed via treating physicians to inform potential participants (documents available for Belgium, Spain, Italy, Germany).
• Physician Referral Letter (K2 Physician Referral Letter documents) for HCP-to-HCP referral to invite eligible patients to sites (country-specific versions present for Belgium, Spain, Italy, Germany).
• HCP fact sheet (K2_HCP fact sheet_EN) to inform healthcare professionals about the study and eligibility (global / Belgium version present).
• Site-level recruitment procedures and informed consent processes documented in K1 recruitment arrangement documents (country-specific K1 documents for Belgium, Italy, Spain, Germany).

Belgium

Earliest CTIS Part Ii Submission Date

19-09-2025

Latest Decision Or Authorization Date

09-04-2026

Processing Time Days

202

Number Of Sites

4

Number Of Participants

57

Germany

Earliest CTIS Part Ii Submission Date

29-09-2025

Latest Decision Or Authorization Date

09-04-2026

Processing Time Days

192

Number Of Sites

5

Number Of Participants

60

Italy

Earliest CTIS Part Ii Submission Date

24-09-2025

Latest Decision Or Authorization Date

09-04-2026

Processing Time Days

197

Number Of Sites

7

Number Of Participants

88

Spain

Earliest CTIS Part Ii Submission Date

25-09-2025

Latest Decision Or Authorization Date

13-04-2026

Processing Time Days

200

Number Of Sites

10

Number Of Participants

124

Primary sponsor

Full Name

BioNTech SE

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Contract research organisations

Name

IQVIA Limited

Responsibilities

Vendor management

Name

Pharmaceutical Research Associates Group B.V.

Responsibilities

Speciality Lab for pharmacokinetics and ADA for BNT326

Name

Almac Clinical Services Limited

Responsibilities

IMP supply managment, secondary packaging and labeling, QP release and distribution

Name

Labcorp Central Laboratory Services SARL

Responsibilities

Specialty Lab, histology, IHC

Name

BioAgilytix Europe GmbH

Responsibilities

Speciality laboratory, pharmacokinetic and ADA for BNT327

Name

Veeva Systems Inc.

Responsibilities

VeevaVault Safety Database

Name

Azenta Germany GmbH

Responsibilities

Long-term storage

Name

Endpoint Clinical Inc.

Third parties

• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Vendor management","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Pharmaceutical Research Associates Group B.V.","duties_or_roles":"Speciality Lab for pharmacokinetics and ADA for BNT326","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Veeva Systems Inc.","duties_or_roles":"VeevaVault Safety Database","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":"Long-term storage","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Specialty Lab, histology, IHC","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"IMP supply managment, secondary packaging and labeling, QP release and distribution","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"BioAgilytix Europe GmbH","duties_or_roles":"Speciality laboratory, pharmacokinetic and ADA for BNT327","organisation_type":"Pharmaceutical company"}