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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Paclitaxel; Drug: Pemetrexed; Drug: Carboplatin; Drug: Pembrolizumab; Drug: Tobemstomig

• Study Type: Interventional
• Enrollment (Actual): 182
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5112
      • Lyell McEwin Hospital
  • Victoria
    • Geelong, Victoria, Australia, 3220
      • Barwon Health
    • Melbourne, Victoria, Australia, 3168
      • Monash Health
• Belgium
  • Brussels, Belgium, 1090
    • UZ Brussel
  • Hasselt, Belgium, 3500
    • Jessa Zkh (Campus Virga Jesse)
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
  • Mechelen, Belgium, 2800
    • AZ St Maarten Campus Leopoldstr
• Brazil
  • Ceará
    • Fortaleza, Ceará, Brazil, 60336-550
      • Crio - Centro Regional Integrado de Oncologia
  • Estado de Bahia
    • Salvador, Bahia, Estado de Bahia, Brazil, 40170-380
      • Nucleo de Oncologia da Bahia - NOB
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 91350-200
      • Hospital Nossa Senhora da Conceicao
    • Porto Alegre, Rio Grande do Sul, Brazil
      • Hospital de Clínicas de Porto Alegre X
  • São Paulo
    • Barretos, São Paulo, Brazil, 14784-400
      • Hospital de Cancer de Barretos
    • São Paulo, São Paulo, Brazil, 01246-000
      • Instituto do Cancer do Estado de Sao Paulo - ICESP
• France
  • Lyon, France, 69008
    • Centre Leon Berard
  • Paris, France, 75679
    • Hôpital Cochin
  • Saint-Herblain, France, 44805
    • Ico Rene Gauducheau
  • Toulouse, France, 31100
    • CHU de Toulouse - Hopital Larrey
• Germany
  • Essen, Germany, 45122
    • Uniklinik Essen
  • Großhansdorf, Germany, 22927
    • LungenClinic Grosshansdorf GmbH
  • Halle, Germany, 06120
    • Krankenhaus Martha-Maria Halle-Doelau
  • Heidelberg, Germany, 69126
    • Thoraxklinik Heidelberg gGmbH
  • Immenhausen, Germany, 34376
    • Lungenfachklinik Immenhausen
• Italy
  • Campania
    • Avellino, Campania, Italy, 83100
      • Azienda Ospedaliera San Giuseppe Moscati
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • AZ.Osp S. Orsola ? Malpighi-Reparto di Oncologia Medica
  • Lazio
    • Rome, Lazio, Italy, 00168
      • Policlinico Universitario "Agostino Gemelli"
  • Liguria
    • Genoa, Liguria, Italy, 16132
      • IRCCS AOU San Martino - IST
  • Lombardy
    • Milan, Lombardy, Italy, 20141
      • Irccs Istituto Europeo Di Oncologia (IEO)
    • Monza, Lombardy, Italy, 20900
      • Asst Di Monza
  • Veneto
    • Padova, Veneto, Italy, 35128
      • IOV - Istituto Oncologico Veneto - IRCCS
• Mexico
  • Distrito Federal, Mexico, 14080
    • Instituto Nacional De Cancerologia
  • Mexico CITY (federal District)
    • Mexico City, Mexico CITY (federal District), Mexico, 03810
      • ONCARE Viaducto Napoles
    • Mexico City, Mexico CITY (federal District), Mexico, 07300
      • AMIISTO Atencion Medica Integral Investigacion y Terapia Oncologica S.A de C.V
• South Korea
  • Busan, South Korea, 49241
    • Pusan National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 08308
    • Korea University Guro Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Málaga, Spain, 29011
    • Hospital Regional Universitario Carlos Haya
  • Balearic Islands
    • Palma de Mallorca, Balearic Islands, Spain, 07198
      • Hospital Son Llatzer
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08908
      • Institut Catala d Oncologia Hospitalet
  • LA Coruna
    • A Coruña, LA Coruna, Spain, 15006
      • Complejo Hospitalario Universitario A Coruña (CHUAC)
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06520
    • Memorial Ankara Hastanesi
  • Ankara, Turkey (Türkiye), 06800
    • Ankara City Hospital
  • Edirne, Turkey (Türkiye), 22030
    • Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi
  • Istanbul, Turkey (Türkiye), 34214
    • Medipol University Medical Faculty
  • Izm?r, Turkey (Türkiye), 35575
    • ?zmir Medical Park
• United States
  • Michigan
    • Detroit, Michigan, United States, 48202-2689
      • Henry Ford Health System
  • Nevada
    • Reno, Nevada, United States, 89502-1576
      • Renown Regional Medical Center Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Drug: Paclitaxel; Participants will receive IV paclitaxel Q3W for four 21-day cycles; Drug: Pemetrexed; Participants will receive IV pemetrexed Q3W until disease progression or unacceptable toxicity; Drug: Carboplatin; Participants will receive IV carboplatin Q3W for four 21-day cycles; Drug: Pembrolizumab; Participants will receive IV pembrolizumab four 21-day cycles
Experimental: 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.	Drug: Paclitaxel; Participants will receive IV paclitaxel Q3W for four 21-day cycles; Drug: Pemetrexed; Participants will receive IV pemetrexed Q3W until disease progression or unacceptable toxicity; Drug: Carboplatin; Participants will receive IV carboplatin Q3W for four 21-day cycles; Drug: Tobemstomig; Participants will receive intravenous (IV) tobemstomig for four 21-day cycles; Other Names: RO7247669

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS is defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.	Randomization to date of first documented disease progression or death (up to approximately 15 months)
Objective Response Rate (ORR)	ORR is defined as the percentage of participants who experience a complete reponse or partial response on two consecutive occasions at least 4 weeks apart as determined by the investigator according to RECIST v1.1.	Up to approximately 15 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from randomization to death from any cause.	From randomization to death from any cause (up to approximately 15 months)
Duration of Response (DOR)	DOR is defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first.	From the first occurrence of a confirmed objective response to disease progression or death from any cause (whichever occurs first) (up to approximately 15 months)
PFS in Participants With PD-L1 Expression		Up to 28 months
OS for Participants With PD-L1 Expression		Up to 28 months
Change in Participant-reported Outcomes as Assessed by the European Organisation for Research and Treatment (EORTC): Physical Functioning	The EORTC Item Library 17 (IL17) physical functioning scale measures a participant's ability to perform a variety of physical activities. Raw scores are calculated by estimating the average of the items that contribute to the scale. Linear transformation is then used to standardize the raw score to a total score range of 0-100. Higher scores for this measure indicate better outcomes.	Baseline to week 12
Change in Participant-reported Outcomes as Assessed by the EORTC: Global Health Status/Quality of Life (GHS/QoL)	The EORTC Item Library 17 (IL17) Global Health Status/Quality of Life (GHS/QoL) scale measures the participant's overall health and quality of health over the last week. Raw scores are calculated by estimating the average of the items that contribute to the scale. Linear transformation is then used to standardize the raw score to a total score range of 0-100. Higher scores for this measure indicate a higher quality of life.	Baseline to week 12
Change in Participant-reported Outcomes as Assessed by the EORTC: Role Functioning	The EORTC Item Library 17 (IL17) role functioning scale measures the degree to which disease or treatment interferes with the participant's work or daily activities. Raw scores are calculated by estimating the average of the items that contribute to the scale. Linear transformation is then used to standardize the raw score to a total score range of 0-100. Higher scores for this measure indicate better outcomes.	Baseline to week 12
Change in Participant-reported Outcomes as Assessed by the EORTC: Lung Cancer Symptoms/How Much Did You Cough	The EORTC IL 85 lung cancer symptoms/how much did you cough measure assesses the severity and frequency of coughing over the past week. The single item is scored on a scale of 1-4, with higher scores indicating worse outcomes.	Baseline to week 12
Change in Participant-reported Outcomes as Assessed by the EORTC: Short of Breath When Rested	The EORTC IL 85 short of breath when rested measure assesses the degree of difficulty breathing while resting over the past week. The single item is scored on a scale of 1-4, with higher scores indicating worse outcomes.	Baseline to week 12
Change in Participant-reported Outcomes as Assessed by the EORTC: Short of Breath When Walked	The EORTC IL 85 short of breath when walked measure assesses the degree of difficulty breathing while walking over the past week. The single item is scored on a scale of 1-4, with higher scores indicating worse outcomes.	Baseline to week 12
Change in Participant-reported Outcomes as Assessed by the EORTC: Short of Breath Climbed Stairs	The EORTC IL 85 short of breath climbed stairs measure assesses the degree of difficulty breathing while climbing stairs over the past week. The single item is scored on a scale of 1-4, with higher scores indicating worse outcomes.	Baseline to week 12
Change in Participant-reported Outcomes as Assessed by the EORTC: Pain in Chest	The EORTC IL 85 pain in chest measure assesses the severity of chest pain over the past week. The single item is scored on a scale of 1-4, with higher scores indicating worse outcomes.	Baseline to week 12
Change in Participant-reported Outcomes as Assessed by the EORTC: Need to Rest	The EORTC IL 132 need to rest measure assesses how often the participant felt the need to rest over the past week. The single item is scored on a scale of 1-4, with higher scores indicating worse outcomes.	Baseline to week 12
Change in Participant-reported Outcomes as Assessed by the EORTC: Felt Weak	The EORTC IL 132 felt weak measure assesses how often the participant felt weak over the past week. The single item is scored on a scale of 1-4, with higher scores indicating worse outcomes.	Baseline to week 12
Change in Participant-reported Outcomes as Assessed by the EORTC: Tired	The EORTC IL 132 tired measure assesses how often the participant felt tired over the past week. The single item is scored on a scale of 1-4, with higher scores indicating worse outcomes.	Baseline to week 12
Change in Participant-reported Outcomes as Assessed by the EORTC: Aches/Pain in Bones	The EORTC IL 188 aches/pain in bones measure assessesthe severity of bone pain over the past week. The single item is scored on a scale of 1-4, with higher scores indicating worse outcomes.	Baseline to week 12
Number of Participants With Adverse Events (AEs)		From the start of treatment to 90 days after the final dose of treatment (up to 28 months)
Maximum Serum Concentration (Cmax) of Tobemstomig		Up to approximately 15 months
Time of Maximum Concentration (Tmax) of Tobemstomig		Up to approximately 15 months
Clearance (CL) of Tobemstomig		Up to approximately 15 months
Volume of Distribution at Steady State (Vss) of Tobemstomig		Up to approximately 15 months
Area Under the Concentration-time Curve (AUC) of Tobemstomig		Up to approximately 15 months
Half-life (T1/2) of Tobemstomig		Up to approximately 15 months
Percentage of Participants With Anti-drug Antibodies (ADAs)		Baseline up to approximately 15 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-LaRoche

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2023
• Primary Completion (Actual): June 20, 2024
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: March 6, 2023
• First Submitted That Met QC Criteria: March 16, 2023
• First Posted (Actual): March 20, 2023

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• 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; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Diterpenes; Pemetrexed; Carboplatin; Paclitaxel; pembrolizumab
• Other Study ID Numbers: BO44178

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No