Clinical trial NCT05775289: A Study of Tobemstomig Plus Platinum-Based Chemotherapy vs Pembrolizumab Plus Platinum-Based Chemotherapy in Participants With Previously Untreated Non-Small Cell Lung Cancer
Official title: A Phase II, Randomized, Multicenter, Double-Blind, Controlled Study of Tobemstomig Plus Platinum-Based Chemotherapy Versus Pembrolizumab Plus Platinum-Based Chemotherapy in Patients With Previously Untreated Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2023-03-20
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of tobemstomig (RO7247669) in combination with platinum-based chemotherapy compared with pembrolizumab plus platinum-based chemotherapy in participants with previously untreated, locally advanced, unresectable (Stage IIIB/IIIC) or metastatic (Stage IV) non-small-cell lung cancer (NSCLC) who are not eligible to receive curative surgery and/or definitive chemoradiotherapy.


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Histologically or cytologically documented locally advanced, unresectable (Stage IIIB/IIIC) or metastatic (Stage IV) NSCLC who are not eligible for curative surgery and/or definitive chemoradiotherapy
* No prior systemic treatment for metastatic NSCLC
* Known tumor PD-L1 status
* Confirmed availability of representative tumor specimens
* Measurable disease
* Life expectancy of at least 12 weeks
* Adequate hematologic and end-organ function
* Negative for HIV, hepatitis B (HBV), and hepatitis C (HCV)
* Adequate cardiovascular function

Exclusion Criteria:

* NSCLC known to have a mutation in the EGFR gene or an ALK fusion oncogene
* Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
* Untreated or clinically unstable spinal cord confession
* History of leptomeningeal disease
* Uncontrolled tumor-related pain
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once a month or more frequently)
* Uncontrolled or symptomatic hypercalcemia
* Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, granulomatosis with polyangiitis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with exceptions defined by the protocol
* History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on the screening chest computed tomography (CT) scan
* Active tuberculosis (TB) or untreated latent TB
* Current treatment with anti-viral therapy for HBV or HCV
* Significant cardiovascular disease within 3 months prior to randomization
* Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
* History of malignancy other than NSCLC within 5 years prior to randomization, with the exception of malignancies with a negligible risk of metastasis or death e.g., 5-year OS\] rate \> 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal breast carcinoma in situ, or Stage I uterine cancer
* Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that could affect patient safety
* Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
* Prior allogeneic stem cell or solid organ transplantation
* Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
* Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during study treatment or within 5 months after the final dose of study treatment
* Treatment with investigational therapy within 28 days prior to initiation of study treatment
* Any anti-cancer therapy, including hormonal therapy, within 21 days prior to initiation of study treatment
* Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including, but not limited to, anti-cytotoxic T lymphocyte-associated protein 4, anti-T cell immunoreceptor with Ig and tyrosine-based inhibition motif domains, anti-PD-1 and anti-PD-L1 therapeutic antibodies, and anti-LAG3) agents
* Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin-2) within 4 weeks or 5 drug-elimination half lives (whichever is longer) prior to initiation of study treatment
* Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[TNF\] agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment
* History of severe allergic anaphylactic reactions to chimeric or humanized antibodies, fusion proteins, or platinum-containing compounds
* Known hypersensitivity to Chinese hamster ovary cell products or to any component of the tobemstomig or pembrolizumab formulation
* Known allergy or hypersensitivity or other contraindication to any component of the chemotherapy regimen the patient may receive during the study
* Pregnancy or breastfeeding

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: From randomization to the first occurrence of disease progression or death from any cause (whichever occurs first) (up to 28 months)
measure: Objective response rate (ORR)
timeFrame: Two consecutive occasions at least 4 weeks apart after a complete response (CR) or partial response (PR) (up to 28 months)
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: From randomization to death from any cause (up to 28 months)
measure: Duration of response (DOR)
timeFrame: From the first occurrence of a confirmed objective response to disease progression or death from any cause (whichever occurs first) (up to 28 months)
measure: PFS in participants with PD-L1 expression
timeFrame: Up to 28 months
measure: OS for participants with PD-L1 expression
timeFrame: Up to 28 months
measure: Change in participant-reported outcomes as assessed by the use of the European Organisation for Research and Treatment (EORTC) item libraries
timeFrame: Baseline to week 12
measure: Percentage of participants with adverse events (AEs)
timeFrame: Up to 28 months
measure: Maximum serum concentration (Cmax) of Tobemstomig
timeFrame: Up to 28 months
measure: Time of maximum concentration (Tmax) of Tobemstomig
timeFrame: Up to 28 months
measure: Clearance (CL) of Tobemstomig
timeFrame: Up to 28 months
measure: Volume of distribution at steady state (Vss) of Tobemstomig
timeFrame: Up to 28 months
measure: Area under the concentration-time curve (AUC) of Tobemstomig
timeFrame: Up to 28 months
measure: Half-life (T1/2) of Tobemstomig
timeFrame: Up to 28 months
measure: Plasma concentration of Carboplatin
timeFrame: Up to 28 weeks
measure: Plasma concentration of pemetrexed
timeFrame: Up to 28 months
measure: Plasma concentration of paclitaxel
timeFrame: Up to 28 months
measure: Percentage of participants with anti-drug antibodies (ADAs)
timeFrame: Baseline up to 28 months
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Reno
country: United States
facility: Renown Regional Medical Center Hospital
state: Nevada
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Lyell McEwin Hospital
state: South Australia
city: Geelong
country: Australia
facility: Barwon Health
state: Victoria
city: Melbourne
country: Australia
facility: Monash Health
state: Victoria
city: Brussel
country: Belgium
facility: UZ Brussel
city: Hasselt
country: Belgium
facility: Jessa Zkh (Campus Virga Jesse)
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Mechelen
country: Belgium
facility: AZ St Maarten Campus Leopoldstr
city: Salvador, Bahia
country: Brazil
facility: Nucleo de Oncologia da Bahia - NOB
state: Bahia
city: Fortaleza
country: Brazil
facility: Crio - Centro Regional Integrado de Oncologia
state: Ceará
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre X
state: Rio Grande Do Sul
city: Barretos
country: Brazil
facility: Hospital de Cancer de Barretos
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo - ICESP
state: São Paulo
city: Lyon
country: France
facility: Centre Leon Berard
city: Paris
country: France
facility: Hopital Cochin
city: Saint Herblain
country: France
facility: Ico Rene Gauducheau
city: Toulouse cedex 9
country: France
facility: CHU de Toulouse - Hôpital Larrey
city: Essen
country: Germany
facility: Uniklinik Essen
city: Großhansdorf
country: Germany
facility: LungenClinic Großhansdorf GmbH
city: Halle (Saale)
country: Germany
facility: Krankenhaus Martha-Maria Halle-Doelau
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg gGmbH
city: Immenhausen
country: Germany
facility: Lungenfachklinik Immenhausen
city: Avellino
country: Italy
facility: Azienda Ospedaliera San Giuseppe Moscati
state: Campania
city: Bologna
country: Italy
facility: AZ.Osp S. Orsola ? Malpighi-Reparto di Oncologia Medica
state: Emilia-Romagna
city: Roma
country: Italy
facility: Policlinico Universitario "Agostino Gemelli"
state: Lazio
city: Genova
country: Italy
facility: IRCCS AOU San Martino - IST
state: Liguria
city: Milano
country: Italy
facility: Irccs Istituto Europeo di Oncologia (IEO)
state: Lombardia
city: Monza
country: Italy
facility: Asst Di Monza
state: Lombardia
city: Padova
country: Italy
facility: IOV - Istituto Oncologico Veneto - IRCCS
state: Veneto
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Ciudad de México
country: Mexico
facility: ONCARE Viaducto Napoles
state: Mexico CITY (federal District)
city: Ciudad de México
country: Mexico
facility: AMIISTO Atencion Medica Integral Investigacion y Terapia Oncologica S.A de C.V
state: Mexico CITY (federal District)
city: Distrito Federal
country: Mexico
facility: Instituto Nacional de Cancerologia
city: San Luis Potosí
country: Mexico
facility: Oncológico Potosino
city: Hospitalet de Llobregat
country: Spain
facility: Institut Catala d Oncologia Hospitalet
state: Barcelona
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llatzer
state: Islas Baleares
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña (CHUAC)
state: LA Coruna
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya
city: Ankara
country: Turkey
facility: Memorial Ankara Hastanesi
city: Ankara
country: Turkey
facility: Ankara City Hospital
city: Edirne
country: Turkey
facility: Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi
city: Istanbul
country: Turkey
facility: Medipol University Medical Faculty
city: Izm?r
country: Turkey
facility: ?zmir Medical Park
Study officials:
affiliation: Hoffmann-LaRoche
name: Clinical Trials
role: STUDY_DIRECTOR
References: