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

A Phase II, Multisite, Open-label Trial of Pumitamig (BNT327) in Combination With Standard-of-care Chemotherapy in First-line and Second-line Non-small Cell Lung Cancer (NSCLC)

This is a Phase II, multisite, open-label study consisting of two parts in participants with advanced/metastatic Non-small Cell Lung Cancer (NSCLC) which progressed after a first-line chemoimmunotherapy to evaluate the combination of pumitamig (also known as BNT327, BMS-986545 or PM8002) with standard of care.

Part 1 is a safety run-in with pumitamig (Dose 1 or Dose 2) plus docetaxel and will include up to 12 participants in total to be treated in Part 1A and 1B sequentially.

Part 2 is a dose expansion at the deemed safe dose of pumitamig plus docetaxel and will include up to 54 participants.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: Pumitamig

Detailed Description

If the dose level (either from Part 1A or 1B) seems tolerable, an internal review committee will decide if the study can proceed to Part 2 and enroll additional participants.

In Part 2, participants who consent will be included in a separate cohort in which they will receive the same treatment as the other participants in Part 2, but in addition to a fresh baseline tumor biopsy, they will be required to provide an on-treatment tumor biopsy sample for additional analyses.

Study participants will receive pumitamig in combination with docetaxel until disease progression, the occurrence of intolerable toxicity, study participant withdrawal, death, study termination or 2-year limit (whichever comes first).

After completion of study treatment, except for participants who withdraw informed consent, a long-term follow-up will be conducted for all participants to record disease progression, subsequent new anticancer treatments, and survival status.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: BioNTech clinical trials patient information; Phone Number: +49 6131 9084; Email: patients@biontech.de

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Recruiting
      • Liverpool Cancer Therapy Centre
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Recruiting
      • Metro South Health - Princess Alexandra Hospital (PAH)
  • South Austraila
    • Adelaide, South Austraila, Australia, 5000
      • Recruiting
      • Cancer Research SA (CRSA)
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Recruiting
      • Hobart Hospital-Royal Hobart Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • One Clinical Research - Hollywood Private Hospital
• South Korea
  • Cheongju-si, South Korea, 28644
    • Recruiting
    • Chungbuk National University Hospital
  • Incheon, South Korea, 21565
    • Recruiting
    • Gachon University Gil Medical Center
  • Seoul, South Korea, 03722
    • Recruiting
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 06351
    • Recruiting
    • Samsung Medical Center
  • Gyeongsangnam-do
    • Jinju, Gyeongsangnam-do, South Korea, 52727
      • Recruiting
      • Gyeongsang National University Hospital (GNUH)
• Spain
  • Barcelona, Spain, 08908
    • Recruiting
    • Institut dInvestigacio Biomedica de Bellvitge (IDIBELL)
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Universitario Fundacion Jimenez Diaz
  • Seville, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46026
    • Recruiting
    • Universitat de Valencia - Hospital Universitari i Politecnic La Fe de Valencia (Hospital La Fe Bulevar Sur)
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01250
    • Recruiting
    • Baskent University Adana Turgut Noyan Application and Research Center Kisla Health Campus
  • Ankara, Turkey (Türkiye), 06520
    • Recruiting
    • Memorial Ankara Hospital
  • Ankara, Turkey (Türkiye), 06800
    • Recruiting
    • Ankara Bilkent City Hospital
  • Antalya, Turkey (Türkiye), 07090
    • Recruiting
    • Memorial Antalya Hospital
  • Istanbul, Turkey (Türkiye), 34752
    • Recruiting
    • Yeditepe University Hospital
  • Zeytinburnu, Turkey (Türkiye), 34010
    • Recruiting
    • Koc Universitesi Hastanesi (Koc University Hospital)
• United Kingdom
  • Cardiff, United Kingdom, CF14 2TL
    • Recruiting
    • Velindre NHS Trust, Velindre Cancer Centre
  • Leeds, United Kingdom, LS9 7TF
    • Recruiting
    • St James's University Hospital - Leeds Teaching Hospitals NHS Trust
  • London, United Kingdom, W1G 6AD
    • Recruiting
    • Sarah Cannon Research Institute
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • The Christie NHS Foundation Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • Recruiting
      • The University of Alabama at Birmingham Hospital
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
  • Kentucky
    • Elizabethtown, Kentucky, United States, 42701
      • Recruiting
      • Baptist Health Hardin
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone - NYU Grossman School of Medicine
  • Texas
    • Houston, Texas, United States, 77090
      • Completed
      • Texas Oncology, P.A.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• 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 per the American Joint Committee on Cancer staging system, 9th edition.

  • Participants must have received minimum two cycles of immunotherapy in first-line treatment to be eligible to this study.
  • Only one prior line of immunotherapy containing regimen is allowed in an advanced/metastatic setting. If 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.
  • Enrollment of participants with primary resistance (best response being radiological progression to prior immunochemotherapy) will be kept below 30% in the overall study population.
• Have at least one measurable lesion as the targeted lesion based on 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.
• Participants must provide tumor tissue samples obtained ≤18 months prior to enrollment. For the additional cohort in Part 2, both baseline (freshly obtained) and on-treatment tumor biopsy samples are required.
• Eastern cooperative oncology group performance status of 0 or 1.
• Adequate organ function as defined in the protocol.

Key Exclusion Criteria:

• Have a known or suspected hypersensitivity to the study treatments, their metabolites or formulation of excipients including polysorbate 80 (see Docetaxel label).
• 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.
• Have received more than one prior lines of therapies in advanced/metastatic setting.
• 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). Note: local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short term use (≤7 days) of corticosteroids for prophylaxis (e.g., prevention of contrast agent allergy) or treatment of non autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens) are allowed.
• Participants who have received prior radiotherapy may be enrolled if they have no acute toxicity related to this therapy.
• Have uncontrolled hypertension or poorly controlled diabetic conditions within 7 days prior to the first dose of study treatment.
• 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.
• Participants with significant risk of hemorrhage as defined in the protocol.
• Have superior vena cava syndrome or symptoms of spinal cord compression.

NOTE: Other protocol defined Inclusion/Exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1A - Pumitamig Dose 1 + docetaxel	Drug: Docetaxel; Intravenous infusion; Drug: Pumitamig; Intravenous infusion; Other Names: BNT327; PM8002; BMS-986545
Experimental: Part 1B - Pumitamig Dose 2 + docetaxel	Drug: Docetaxel; Intravenous infusion; Drug: Pumitamig; Intravenous infusion; Other Names: BNT327; PM8002; BMS-986545
Experimental: Part 2: Selected doses of pumitamig + docetaxel; Pumitamig and docetaxel will be administered at the dose level recommended by an internal review committee based on the observed safety profile from Part 1.	Drug: Docetaxel; Intravenous infusion; Drug: Pumitamig; Intravenous infusion; Other Names: BNT327; PM8002; BMS-986545

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 - Occurrence of dose limiting toxicities (DLTs)	During the DLT evaluation period by dose level	Up to 21 days after first dose of investigational medicinal product (IMP)
Part 1 and Part 2 - Occurrence of pumitamig treatment emergent adverse events, treatment-related adverse events, treatment emergent serious adverse events, treatment-related serious adverse events, and adverse events of special interest	Graded according to the (United States) National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0)	From initiation of the first dose of IMP to the 90-day Follow-Up visit
Part 1 and Part 2 - Occurrence of dose interruption, dose reduction, and/or participant discontinuation due to adverse events		From initiation of the first dose of IMP until the 90-day Safety Follow-up visit
Part 1 and Part 2 - Objective response rate	Defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) (per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) based on investigator's review) is observed as best overall response.	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 and Part 2 - Duration of Response	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.	Up to approximately 2 years
Part 1 and Part 2- Progression-free Survival	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.	Up to approximately 2 years
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 (including nodal [short axis] and non-nodal [longest axis] lesions).	Up to approximately 2 years
Part 1 and Part 2 - Disease Control Rate	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.	Up to approximately 2 years
Part 1 and Part 2 - Time to Response	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).	Up to approximately 2 years
Part 1 and Part 2 - Overall Survival	Defined as the time from first dose of IMP to death from any cause	Up to approximately 2 years
Part 1 and Part 2 - Pharmacokinetic assessment: Maximum concentration (Cmax) derived from serum concentration of pumitamig		From pre-dose to the end of study treatment (up to approximately 2 years)
Part 1 and Part 2 - Number of participants developing detectable anti-pumitamig antibodies in serum		From pre-dose to the end of study treatment (up to approximately 2 years)

Collaborators and Investigators

• Sponsor: BioNTech SE
• Collaborators: BioNTech (Shanghai) Pharmaceuticals Co., Ltd.
• Investigators: Study Director: BioNTech Responsible Person, BioNTech SE

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2025
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: February 20, 2025
• First Submitted That Met QC Criteria: February 20, 2025
• First Posted (Actual): February 24, 2025

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; Bispecific antibody; Second-line treatment; Programmed death-ligand 1 (PD-L1); Combination with chemotherapy; Combination with other investigational agents; Vascular endothelial growth factor (VEGF) A
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Docetaxel
• Other Study ID Numbers: BNT327-07; 2024-518279-80-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No