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

Официальное название

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)

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Pumitamig
  Intravenous infusion
• Препарат Docetaxel
  Intravenous infusion

Первичные конечные точки

• Part 1 - Occurrence of dose limiting toxicities (DLTs) [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: From initiation of the first dose of IMP until the 90-day Safety Follow-up visit]
• Part 1 and Part 2 - Objective response rate [Срок оценки: Up to approximately 2 years]

Вторичные конечные точки (8)

• Part 1 and Part 2 - Duration of Response [Срок оценки: Up to approximately 2 years]
• Part 1 and Part 2- Progression-free Survival [Срок оценки: Up to approximately 2 years]
• Part 1 and Part 2 - Depth of Response [Срок оценки: Up to approximately 2 years]
• Part 1 and Part 2 - Disease Control Rate [Срок оценки: Up to approximately 2 years]
• Part 1 and Part 2 - Time to Response [Срок оценки: Up to approximately 2 years]
• Part 1 and Part 2 - Overall Survival [Срок оценки: Up to approximately 2 years]
• Part 1 and Part 2 - Pharmacokinetic assessment: Maximum concentration (Cmax) derived from serum concentration of pumitamig [Срок оценки: 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 [Срок оценки: From pre-dose to the end of study treatment (up to approximately 2 years)]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Turkey (Türkiye) · 6 центров

• Baskent University Adana Turgut Noyan Application and Research Center Kisla Health Campus — Adana
• Memorial Ankara Hospital — Ankara
• Ankara Bilkent City Hospital — Ankara
• Memorial Antalya Hospital — Antalya
• Yeditepe University Hospital — Istanbul
• Koc Universitesi Hastanesi (Koc University Hospital) — Zeytinburnu

США · 5 центров

• The University of Alabama at Birmingham Hospital — Birmingham
• Moffitt Cancer Center — Tampa
• Baptist Health Hardin — Elizabethtown
• NYU Langone - NYU Grossman School of Medicine — New York
• Texas Oncology, P.A. — Houston

Австралия · 5 центров

• Liverpool Cancer Therapy Centre — Liverpool
• Metro South Health - Princess Alexandra Hospital (PAH) — Woolloongabba
• Cancer Research SA (CRSA) — Adelaide
• Hobart Hospital-Royal Hobart Hospital — Hobart
• One Clinical Research - Hollywood Private Hospital — Nedlands

South Korea · 5 центров

• Gyeongsang National University Hospital (GNUH) — Jinju
• Chungbuk National University Hospital — Cheongju-si
• Gachon University Gil Medical Center — Incheon
• Severance Hospital, Yonsei University Health System — Seoul
• Samsung Medical Center — Seoul

Испания · 5 центров

• Institut dInvestigacio Biomedica de Bellvitge (IDIBELL) — Barcelona
• Hospital Universitario Ramón y Cajal — Madrid
• Hospital Universitario Fundacion Jimenez Diaz — Madrid
• Hospital Universitario Virgen del Rocio — Seville
• Universitat de Valencia - Hospital Universitari i Politecnic La Fe de Valencia (Hospital L — Valencia

Великобритания · 4 центра

• Velindre NHS Trust, Velindre Cancer Centre — Cardiff
• St James's University Hospital - Leeds Teaching Hospitals NHS Trust — Leeds
• Sarah Cannon Research Institute — London
• The Christie NHS Foundation Trust — Manchester

Идентификаторы

NCT: NCT06841055 · BNT327-07 · 2024-518279-80-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗