Safety and preliminary efficacy of pumitamig (BNT327), an investigational therapy for patients with non-small cell lung cancer in combination with chemotherapy as first-line or second-line treatment

Overview

Sponsor-declared trial summary

Key facts

Sponsor

BioNTech SE

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 Sep 2025 → ongoing

Decision date (initial)

2025-07-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-518279-80-00

ClinicalTrials.gov

NCT06841055

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess the safety and tolerability of pumitamig (BNT327) in combination with docetaxel (Part 1 and overall) in the trial population (participants with advanced/metastatic NSCLC which progressed after a first-line chemoimmunotherapy). To evaluate the efficacy of pumitamig (BNT327) with docetaxel in the trial population.

Secondary objectives 3

1. To evaluate other efficacy measures of pumitamig in combination with docetaxel in the trial population.
2. To characterize the pharmacokinetics (PK) of pumitamig after administration of pumitamigin combination with docetaxel in the trial population.
3. To evaluate the immunogenicity of pumitamig in combination with docetaxel in the trial population.

Conditions and MedDRA coding

Non-small Cell Lung Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Have histologically or cytologically confirmed diagnosis of Stage IV NSCLC that has documented radiographic progression on one or after one prior line of systemic treatment (programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitor and platinum-based chemotherapy concomitantly) in advanced/metastatic setting. Participants must have received a minimum 2 cycles of immunotherapy in first-line treatment to be eligible to this trial. Only 1 prior line of immunotherapy containing regimen is allowed in an advanced/metastatic setting. If a participant had received adjuvant immunotherapy, the disease-free interval (after the last dose of adjuvant immunotherapy) should be at least 6 months. Historical PD-L1 results must be available. Participants with actionable genetic alterations may be enrolled if they received locally approved and available targeted agent in combination with immunotherapy in first-line advanced/metastatic setting.
2. Have at least one measurable lesion as the targeted lesion based on response evaluation criteria in solid tumors version 1.1 (RECIST v1.1). Tumor lesions situated in a previously irradiated area are considered measurable if progression has been documented after irradiation. Historical images within 28 days of the screening visit may be accepted as a screening image if deemed acceptable in the opinion of the investigator.
3. Eastern cooperative oncology group performance (ECOG) status of 0 or 1.
4. Adequate organ function.
5. Participants must provide tumor tissue samples either from a freshly obtained biopsy or archival tissue obtained ≤18 months prior to enrollment: a) In these participants an optional on-treatment tumor biopsy is recommended, if medically feasible. b) For the Biomarker Cohort, both baseline (freshly obtained) and on-treatment tumor biopsy samples are required. c) Despite best efforts, if tumor tissue specimen is not available, discussion with the sponsor’s Medical Monitor is required for enrollment.

Exclusion criteria 8

1. Have a known or suspected hypersensitivity to the study treatments, their metabolites or formulation of excipients including polysorbate 80 (see Docetaxel label).
2. Participants who received prior treatment with anti-vascular endothelial growth factor (VEGF) monoclonal antibody, or anti-PD-(L)-1/aVEGF bispecific antibody or docetaxel as monotherapy or in combination with other agents.
3. Have received more than one prior lines of therapies in advanced/metastatic setting.
4. Have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 7 days prior to the initiation of study treatment (except for docetaxel premedication).
5. Have uncontrolled hypertension or poorly controlled diabetic conditions prior to study treatment.
6. Have a serious or non-healing wound, or (incompletely healed) bone fracture. This includes history (within 6 months prior to study entry) or risk of abdominal fistula, tracheoesophageal fistula, gastrointestinal perforation, or intra abdominal abscess or esophageal and gastric varices, or acute gastrointestinal bleeding. In addition, the participant must have undergone correction (or spontaneous healing) of the perforation/fistula and/or the underlying process causing the fistula/perforation.
7. Participants with significant risk of hemorrhage.
8. Have superior vena cava syndrome or symptoms of spinal cord compression.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Part 1: Occurrence of dose-limiting toxicities (DLTs) during the DLT-evaluation period by dose level. Time Frame: up to 21 days after first dose of investigational medicinal product (IMP).
2. Part 1 and Part 2: Occurrence of pumitamig treatment-emergent adverse events (TEAEs), TRAEs, treatment-emergent serious adverse events (TESAEs), treatment-related serious adverse events (TRSAEs), and adverse events of special interest (AESIs) graded according to the (US) National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). From initiation of the first dose of IMP to the 90-day Follow-Up visit.
3. Part 1 and Part 2: Occurrence of dose interruption, dose reduction, and/or participant discontinuation due to adverse events (AEs). Time Frame: from initiation of the first dose of IMP until the 90-day Safety Follow-up visit.
4. Part 1 and Part 2: Objective response rate (ORR) defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR per RECIST v1.1 based on investigator’s review is observed as best overall response). Time Frame: Up to approximately 2 years.

Secondary endpoints 8

1. Part 1 and Part 2: Duration of response (DOR) defined as the time from first objective response (CR or PR per RECIST v1.1 based on the investigator’s assessment) to first occurrence of objective tumor progression (progressive disease, per RECIST v1.1 based on the investigator’s assessment) or death from any cause, whichever occurs first. Time Frame: Up to approximately 2 years.
2. Part 1 and Part 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 per RECIST v1.1) or death from any cause, whichever occurs first. Time Frame: Up to approximately 2 years.
3. Part 1 and Part 2: Depth of Response: Defined as the maximum percent reduction from baseline in tumor size measured by sum of target lesion diameter. Time Frame: Up to approximately 2 years.
4. Part 1 and Part 2: Disease Control Rate (DCR) defined as the proportion of participants with confirmed CR, confirmed PR, or stable disease (per RECIST v1.1 based on the investigator’s assessment) as best overall response. Time Frame: Up to approximately 2 years.
5. Part 1 and Part 2: Time to Response (TTR) defined as the time from first dose of IMP to first objective response (CR or PR per RECIST v1.1 based on the investigator’s assessment). Time Frame: Up to approximately 2 years.
6. Part 1 and Part 2: Overall Survival (OS) defined as the time from first dose of IMP to death from any cause. Time Frame: Up to approximately 2 years.
7. Part 1 and Part 2: Based on pumitamig concentrations in serum, the PK parameter Cmax
8. Part 1 and Part 2: Incidence of detectable anti-pumitamig antibodies in serum from baseline to the end of trial treatment.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

BioNTech SE

Sponsor organisation

BioNTech SE

Address

An Der Goldgrube 12, Oberstadt Oberstadt

City

Mainz

Postcode

55131

Country

Germany

Scientific contact point

Organisation

BioNTech SE

Contact name

Clinical Trial Information Desk

Public contact point

Organisation

BioNTech SE

Contact name

Clinical Trial Information Desk

Third parties 6

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 15 files

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

Application history

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