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NCT06841055PHASE2Recruiting

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

BioNTech SE

Start Date

3/3/2025

Completion Date

10/1/2028

Summary

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.

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

Pumitamig

DRUG

Docetaxel

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Conditions

Non-small Cell Lung Cancer

Locations

The University of Alabama at Birmingham Hospital

Birmingham, Alabama 35249

United States

Moffitt Cancer Center

Tampa, Florida 33612

United States

Baptist Health Hardin

Elizabethtown, Kentucky 42701

United States

NYU Langone - NYU Grossman School of Medicine

New York, New York 10016

United States

Texas Oncology, P.A.

Houston, Texas 77090

United States

Liverpool Cancer Therapy Centre

Liverpool, New South Wales 2170

Australia

Metro South Health - Princess Alexandra Hospital (PAH)

Woolloongabba, Queensland 4102

Australia

Cancer Research SA (CRSA)

Adelaide, South Austraila 5000

Australia

Hobart Hospital-Royal Hobart Hospital

Hobart, Tasmania 7000

Australia

One Clinical Research - Hollywood Private Hospital

Nedlands, Western Australia 6009

Australia

Gyeongsang National University Hospital (GNUH)

Jinju, Gyeongsangnam-do 52727

South Korea

Chungbuk National University Hospital

Cheongju-si, 28644

South Korea

Gachon University Gil Medical Center

Incheon, 21565

South Korea

Severance Hospital, Yonsei University Health System

Seoul, 03722

South Korea

Samsung Medical Center

Seoul, 06351

South Korea

Institut dInvestigacio Biomedica de Bellvitge (IDIBELL)

Barcelona, 08908

Spain

Hospital Universitario Ramón y Cajal

Madrid, 28034

Spain

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040

Spain

Hospital Universitario Virgen del Rocio

Seville, 41013

Spain

Universitat de Valencia - Hospital Universitari i Politecnic La Fe de Valencia (Hospital La Fe Bulevar Sur)

Valencia, 46026

Spain

Baskent University Adana Turgut Noyan Application and Research Center Kisla Health Campus

Adana, 01250

Turkey (Türkiye)

Memorial Ankara Hospital

Ankara, 06520

Turkey (Türkiye)

Ankara Bilkent City Hospital

Ankara, 06800

Turkey (Türkiye)

Memorial Antalya Hospital

Antalya, 07090

Turkey (Türkiye)

Yeditepe University Hospital

Istanbul, 34752

Turkey (Türkiye)

Koc Universitesi Hastanesi (Koc University Hospital)

Zeytinburnu, 34010

Turkey (Türkiye)

Velindre NHS Trust, Velindre Cancer Centre

Cardiff, CF14 2TL

United Kingdom

St James's University Hospital - Leeds Teaching Hospitals NHS Trust

Leeds, LS9 7TF

United Kingdom

Sarah Cannon Research Institute

London, W1G 6AD

United Kingdom

The Christie NHS Foundation Trust

Manchester, M20 4BX

United Kingdom