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 (Estimated): 180
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: BO44178 https://forpatients.roche.com/; Phone Number: 888-662-6728; Email: global-roche-genentech-trials@gene.com

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
    • Clayton, Victoria, Australia, 3168
      • Monash Health
    • Geelong, Victoria, Australia, 3220
      • Barwon Health
• Belgium
  • Brussel, Belgium, 1090
    • UZ Brussel
  • Charleroi, Belgium, 6000
    • GHdC Site Notre Dame
  • Hasselt, Belgium, 3500
    • Jessa Zkh (Campus Virga Jesse)
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
  • Mechelen, Belgium, 2800
    • AZ St Maarten Campus Leopoldstr
• Brazil
  • BA
    • Salvador, Bahia, BA, Brazil, 40170-380
      • Nucleo de Oncologia da Bahia - NOB
  • CE
    • Fortaleza, CE, Brazil, 60336-232
      • Crio - Centro Regional Integrado de Oncologia
  • RS
    • Porto Alegre, RS, Brazil
      • Hospital de Clínicas de Porto Alegre X
    • Porto Alegre, RS, Brazil, 90040-373
      • Hospital Nossa Senhora da Conceicao
  • SP
    • Barretos, SP, Brazil, 14784-400
      • Hospital de Cancer de Barretos
    • Sao Paulo, SP, Brazil, 01246-000
      • Instituto do Cancer do Estado de Sao Paulo - ICESP
• Canada
  • Ontario
    • Oshawa, Ontario, Canada, L1G 2B9
      • Lakeridge Health Oshawa
    • Ottawa, Ontario, Canada, K1Y 4E9
      • Ottawa Hospital Research Institute
    • Windsor, Ontario, Canada, N8W 1L9
      • Windsor Regional Hospital
• France
  • Besancon, France, 25030
    • Hopital Jean Minjoz; Pneumologie
  • Lyon, France, 69008
    • Centre Leon Berard
  • Paris, France, 75014
    • Hopital Cochin; Unite Fonctionnelle D Oncologie
  • Saint Herblain, France, 44805
    • Ico Rene Gauducheau; Oncologie
  • Strasbourg, France, 67065
    • Centre Paul Strauss; Oncologie Medicale
  • Toulouse cedex 9, France, 31100
    • CHU de Toulouse - Hôpital Larrey; Service de pneumologie et oncologie pneumologique
• Germany
  • Essen, Germany, 45122
    • Uniklinik Essen
  • Großhansdorf, Germany, 22927
    • LungenClinic Großhansdorf GmbH; Klinische Forschung
  • Halle (Saale), 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
    • Roma, Lazio, Italy, 00168
      • Policlinico Universitario "Agostino Gemelli"; U.O.C. Oncologia Medica
  • Liguria
    • Genova, Liguria, Italy, 16132
      • IRCCS AOU San Martino - IST
  • Lombardia
    • Milano, Lombardia, Italy, 20141
      • Irccs Istituto Europeo di Oncologia (IEO); Divisione di Oncologia
    • Monza, Lombardia, Italy, 20900
      • ASST di Monza
  • Veneto
    • Padova, Veneto, Italy, 35128
      • IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II
• Korea, Republic of
  • Busan, Korea, Republic of, 602-739
    • Pusan National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 08308
    • Korea University Guro Hospital
• Mexico
  • Mexico City, Mexico, 14080
    • Instituto Nacional de Cancerologia; Oncology
  • San Luis Potosí, Mexico, 78209
    • Oncologico Potosino
  • Mexico CITY (federal District)
    • Ciudad de México, Mexico CITY (federal District), Mexico, 03810
      • ONCARE Viaducto Napoles
    • Ciudad de México, Mexico CITY (federal District), Mexico, 07300
      • AMIISTO Atencion Medica Integral Investigacion y Terapia Oncologica S.A de C.V
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron; Oncology
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre; Servicio de Oncologia
  • Malaga, Spain, 29011
    • Hospital Regional Universitario Carlos Haya; Servicio de Oncologia
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08908
      • Institut Catala d Oncologia Hospitalet
  • Islas Baleares
    • Palma de Mallorca, Islas Baleares, Spain, 07198
      • Hospital Son Llatzer
  • LA Coruña
    • A Coruña, LA Coruña, Spain, 15006
      • Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Oncologia
• Turkey
  • Ankara, Turkey, 06520
    • Memorial Ankara Hastanesi
  • Ankara, Turkey, 06800
    • Ankara City Hospital; Oncology
  • Edirne, Turkey, 22030
    • Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi
  • Istanbul, Turkey, 34214
    • Medipol University Medical Faculty; Oncology Department
  • Izmir, Turkey
    • ?zmir Medical Park; Onkoloji
• United States
  • Alabama
    • Mobile, Alabama, United States, 36604
      • Mitchell Cancer Institute; Pharmacy
  • Michigan
    • Detroit, Michigan, United States, 48202-2689
      • Henry Ford Health System; Hematology/Oncology
  • Nevada
    • Reno, Nevada, United States, 89502-1576
      • Renown Regional Medical Center Hospital
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Health System; MD Anderson Cancer Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University Medical Center Main 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	Time Frame
Progression-free survival (PFS)	From randomization to the first occurrence of disease progression or death from any cause (whichever occurs first) (up to 58 months)
Objective response rate (ORR)	Two consecutive occasions at least 4 weeks apart after a complete response (CR) or partial response (PR) (up to 58 months)

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	From randomization to death from any cause (up to 58 months)
Duration of response (DOR)	From the first occurrence of a confirmed objective response to disease progression or death from any cause (whichever occurs first) (up to 58 months)
PFS in participants with PD-L1 expression	Up to 58 months
OS for participants with PD-L1 expression	Up to 58 months
Change in participant-reported outcomes as assessed by the use of the European Organisation for Research and Treatment (EORTC) item libraries	Baseline to week 12
Percentage of participants with adverse events (AEs)	Up to 58 months
Plasma concentration of Carboplatin	Up to 58 weeks
Plasma concentration of pemetrexed	Up to 58 months
Plasma concentration of paclitaxel	Up to 58 months
Percentage of participants with anti-drug antibodies (ADAs)	Baseline up to 58 months
Maximum serum concentration (Cmax) of Tobemstomig	Up to 58 months
Time of maximum concentration (Tmax) of Tobemstomig	Up to 58 months
Clearance (CL) of Tobemstomig	Up to 58 months
Volume of distribution at steady state (Vss) of Tobemstomig	Up to 58 months
Area under the concentration-time curve (AUC) of Tobemstomig	Up to 58 months
Half-life (T1/2) of Tobemstomig	Up to 58 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 (Estimated): March 30, 2026
• Study Completion (Estimated): March 30, 2028

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): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Folic Acid Antagonists; Carboplatin; Paclitaxel; Pembrolizumab; Pemetrexed
• Other Study ID Numbers: BO44178

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

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