A Study of Tobemstomig Plus Platinum-Based Chemotherapy vs Pembrolizumab Plus Platinum-Based Chemotherapy in Participants With Previously Untreated Non-Small Cell Lung Cancer
- Conditions
- Non-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT05775289
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 180
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B: Pembrolizumab + Platinum-Based Chemotherapy Pembrolizumab 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. Arm B: Pembrolizumab + Platinum-Based Chemotherapy Pemetrexed 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. Arm A: Tobemstomig + Platinum-Based Chemotherapy Tobemstomig 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. Arm A: Tobemstomig + Platinum-Based Chemotherapy Paclitaxel 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. Arm A: Tobemstomig + Platinum-Based Chemotherapy Carboplatin 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. Arm A: Tobemstomig + Platinum-Based Chemotherapy Pemetrexed 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. Arm B: Pembrolizumab + Platinum-Based Chemotherapy Paclitaxel 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. Arm B: Pembrolizumab + Platinum-Based Chemotherapy Carboplatin 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.
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) From randomization to the first occurrence of disease progression or death from any cause (whichever occurs first) (up to 28 months) Objective response rate (ORR) Two consecutive occasions at least 4 weeks apart after a complete response (CR) or partial response (PR) (up to 28 months)
- Secondary Outcome Measures
Name Time Method Overall survival (OS) From randomization to death from any cause (up to 28 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 28 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 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 28 months Maximum serum concentration (Cmax) of Tobemstomig Up to 28 months Clearance (CL) of Tobemstomig Up to 28 months Time of maximum concentration (Tmax) of Tobemstomig Up to 28 months Volume of distribution at steady state (Vss) of Tobemstomig Up to 28 months Area under the concentration-time curve (AUC) of Tobemstomig Up to 28 months Half-life (T1/2) of Tobemstomig Up to 28 months Plasma concentration of Carboplatin Up to 28 weeks Plasma concentration of pemetrexed Up to 28 months Plasma concentration of paclitaxel Up to 28 months Percentage of participants with anti-drug antibodies (ADAs) Baseline up to 28 months
Trial Locations
- Locations (51)
Krankenhaus Martha-Maria Halle-Doelau
🇩🇪Halle (Saale), 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"
🇮🇹Roma, Lazio, Italy
IRCCS AOU San Martino - IST
🇮🇹Genova, Liguria, Italy
Irccs Istituto Europeo di Oncologia (IEO)
🇮🇹Milano, Lombardia, Italy
Asst Di Monza
🇮🇹Monza, Lombardia, Italy
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Renown Regional Medical Center Hospital
🇺🇸Reno, Nevada, United States
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Lyell McEwin Hospital
🇦🇺Adelaide, South Australia, Australia
Jessa Zkh (Campus Virga Jesse)
🇧🇪Hasselt, Belgium
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
AZ St Maarten Campus Leopoldstr
🇧🇪Mechelen, Belgium
Nucleo de Oncologia da Bahia - NOB
🇧🇷Salvador, Bahia, Bahia, Brazil
Crio - Centro Regional Integrado de Oncologia
🇧🇷Fortaleza, Ceará, 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
🇧🇷Sao Paulo, São Paulo, Brazil
Centre Leon Berard
🇫🇷Lyon, France
LungenClinic Großhansdorf GmbH
🇩🇪Großhansdorf, Germany
IOV - Istituto Oncologico Veneto - IRCCS
🇮🇹Padova, Veneto, Italy
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Instituto Nacional de Cancerologia
🇲🇽Distrito Federal, Mexico
Oncológico Potosino
🇲🇽San Luis Potosí, Mexico
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Regional Universitario Carlos Haya
🇪🇸Malaga, Spain
Memorial Ankara Hastanesi
🇹🇷Ankara, Turkey
Ankara City Hospital
🇹🇷Ankara, Turkey
Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi
🇹🇷Edirne, Turkey
Medipol University Medical Faculty
🇹🇷Istanbul, Turkey
?zmir Medical Park
🇹🇷Izm?r, Turkey
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Barwon Health
🇦🇺Geelong, Victoria, Australia
Monash Health
🇦🇺Melbourne, Victoria, Australia
UZ Brussel
🇧🇪Brussel, Belgium
Hopital Cochin
🇫🇷Paris, France
Ico Rene Gauducheau
🇫🇷Saint Herblain, France
CHU de Toulouse - Hôpital Larrey
🇫🇷Toulouse cedex 9, France
Uniklinik Essen
🇩🇪Essen, Germany
Thoraxklinik Heidelberg gGmbH
🇩🇪Heidelberg, Germany
Lungenfachklinik Immenhausen
🇩🇪Immenhausen, Germany
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
ONCARE Viaducto Napoles
🇲🇽Ciudad de México, Mexico CITY (federal District), Mexico
AMIISTO Atencion Medica Integral Investigacion y Terapia Oncologica S.A de C.V
🇲🇽Ciudad de México, Mexico CITY (federal District), Mexico
Institut Catala d Oncologia Hospitalet
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Hospital Son Llatzer
🇪🇸Palma de Mallorca, Islas Baleares, Spain
Complejo Hospitalario Universitario A Coruña (CHUAC)
🇪🇸A Coruña, LA Coruna, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain