A Study of Tobemstomig Plus Platinum-Based Chemotherapy vs Pembrolizumab Plus Platinum-Based Chemotherapy in Participants With Previously Untreated Non-Small Cell Lung Cancer

NCT ID: NCT05775289

Last Updated: 2025-11-19

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 182 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-15
• Study Completion Date: 2026-06-01

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.

Conditions

Non-small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Arm A: Tobemstomig + Platinum-Based Chemotherapy

Participants with non-squamous (NSQ) NSCLC will receive induction treatment with blinded tobemstomig in combination with pemetrexed and carboplatin, all on Day 1 every 3 weeks (Q3W) for four 21-day cycles, followed by Q3W maintenance therapy with blinded tobemstomig together with pemetrexed until disease progression or treatment discontinuation.

Participants with squamous (SQ) NSCLC will receive blinded tobemstomig in combination with paclitaxel and carboplatin, all on Day 1 Q3W for four 21 day cycles, followed by blinded tobemstomig (on Day 1) Q3W until disease progression or treatment discontinuation.

Group Type: EXPERIMENTAL

Tobemstomig

Intervention Type: DRUG

Participants will receive intravenous (IV) tobemstomig for four 21-day cycles

Paclitaxel

Intervention Type: DRUG

Participants will receive IV paclitaxel Q3W for four 21-day cycles

Pemetrexed

Intervention Type: DRUG

Participants will receive IV pemetrexed Q3W until disease progression or unacceptable toxicity

Carboplatin

Intervention Type: DRUG

Participants will receive IV carboplatin Q3W for four 21-day cycles

Arm B: Pembrolizumab + Platinum-Based Chemotherapy

Participants with NSQ NSCLC will receive induction treatment with blinded pembrolizumab in combination with pemetrexed and carboplatin, all on Day 1 Q3W for four 21-day cycles, followed by a maintenance therapy with blinded pembrolizumab together with pemetrexed Q3W until disease progression or treatment discontinuation.

Participants with SQ NSCLC will receive blinded pembrolizumab in combination with paclitaxel and carboplatin, all on Day 1 Q3W for four 21-day cycles, followed by blinded pembrolizumab (on Day 1) Q3W until disease progression or treatment discontinuation.

Group Type: ACTIVE_COMPARATOR

Pembrolizumab

Intervention Type: DRUG

Participants will receive IV pembrolizumab four 21-day cycles

Paclitaxel

Intervention Type: DRUG

Participants will receive IV paclitaxel Q3W for four 21-day cycles

Pemetrexed

Intervention Type: DRUG

Participants will receive IV pemetrexed Q3W until disease progression or unacceptable toxicity

Carboplatin

Intervention Type: DRUG

Participants will receive IV carboplatin Q3W for four 21-day cycles

Interventions

Tobemstomig

Participants will receive intravenous (IV) tobemstomig for four 21-day cycles

Intervention Type: DRUG

Pembrolizumab

Participants will receive IV pembrolizumab four 21-day cycles

Intervention Type: DRUG

Paclitaxel

Participants will receive IV paclitaxel Q3W for four 21-day cycles

Intervention Type: DRUG

Pemetrexed

Participants will receive IV pemetrexed Q3W until disease progression or unacceptable toxicity

Intervention Type: DRUG

Carboplatin

Participants will receive IV carboplatin Q3W for four 21-day cycles

Intervention Type: DRUG

Other Intervention Names

RO7247669

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-LaRoche

Locations

Henry Ford Health System

Detroit, Michigan, United States

Renown Regional Medical Center Hospital

Reno, Nevada, United States

Westmead Hospital

Westmead, New South Wales, Australia

Lyell McEwin Hospital

Adelaide, South Australia, Australia

Barwon Health

Geelong, Victoria, Australia

Monash Health

Melbourne, Victoria, Australia

UZ Brussel

Brussels, , Belgium

Jessa Zkh (Campus Virga Jesse)

Hasselt, , Belgium

UZ Leuven Gasthuisberg

Leuven, , Belgium

AZ St Maarten Campus Leopoldstr

Mechelen, , Belgium

Crio - Centro Regional Integrado de Oncologia

Fortaleza, Ceará, Brazil

Nucleo de Oncologia da Bahia - NOB

Salvador, Bahia, Estado de Bahia, Brazil

Hospital Nossa Senhora da Conceicao

Porto Alegre, Rio Grande do Sul, Brazil

Hospital de Clínicas de Porto Alegre X

Porto Alegre, Rio Grande do Sul, Brazil

Hospital de Cancer de Barretos

Barretos, São Paulo, Brazil

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, Brazil

Centre Leon Berard

Lyon, , France

Hopital Cochin

Paris, , France

Ico Rene Gauducheau

Saint-Herblain, , France

CHU de Toulouse - Hôpital Larrey

Toulouse, , France

Uniklinik Essen

Essen, , Germany

LungenClinic Großhansdorf GmbH

Großhansdorf, , Germany

Krankenhaus Martha-Maria Halle-Doelau

Halle, , Germany

Thoraxklinik Heidelberg gGmbH

Heidelberg, , Germany

Lungenfachklinik Immenhausen

Immenhausen, , Germany

Azienda Ospedaliera San Giuseppe Moscati

Avellino, Campania, Italy

AZ.Osp S. Orsola ? Malpighi-Reparto di Oncologia Medica

Bologna, Emilia-Romagna, Italy

Policlinico Universitario "Agostino Gemelli"

Rome, Lazio, Italy

IRCCS AOU San Martino - IST

Genoa, Liguria, Italy

Irccs Istituto Europeo di Oncologia (IEO)

Milan, Lombardy, Italy

Asst Di Monza

Monza, Lombardy, Italy

IOV - Istituto Oncologico Veneto - IRCCS

Padua, Veneto, Italy

ONCARE Viaducto Napoles

Mexico City, Mexico CITY (federal District), Mexico

AMIISTO Atencion Medica Integral Investigacion y Terapia Oncologica S.A de C.V

Mexico City, Mexico CITY (federal District), Mexico

Instituto Nacional de Cancerologia

Distrito Federal, , Mexico

Pusan National University Hospital

Busan, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Korea University Guro Hospital

Seoul, , South Korea

Hospital Son Llatzer

Palma de Mallorca, Balearic Islands, Spain

Institut Catala d Oncologia Hospitalet

L'Hospitalet de Llobregat, Barcelona, Spain

Complejo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, LA Coruna, Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Regional Universitario Carlos Haya

Málaga, , Spain

Memorial Ankara Hastanesi

Ankara, , Turkey (Türkiye)

Ankara City Hospital

Ankara, , Turkey (Türkiye)

Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi

Edirne, , Turkey (Türkiye)

Medipol University Medical Faculty

Istanbul, , Turkey (Türkiye)

?zmir Medical Park

Izm?r, , Turkey (Türkiye)

Countries

United States; Australia; Belgium; Brazil; France; Germany; Italy; Mexico; South Korea; Spain; Turkey (Türkiye)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

BO44178

Identifier Type: -

Identifier Source: org_study_id