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

Non-small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05775289
• Other study ID #: BO44178
• Status: Recruiting
• Phase: Phase 2
• Start date: March 15, 2023
• Est. completion date: March 30, 2028

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: BO44178 https://forpatients.roche.com
• Phone: 888-662-6728
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: March 30, 2028
• Est. primary completion date: March 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• Tobemstomig
Participants will receive intravenous (IV) tobemstomig for four 21-day cycles
• Pembrolizumab
Participants will receive IV pembrolizumab four 21-day cycles
• Paclitaxel
Participants will receive IV paclitaxel Q3W for four 21-day cycles
• Pemetrexed
Participants will receive IV pemetrexed Q3W until disease progression or unacceptable toxicity
• Carboplatin
Participants will receive IV carboplatin Q3W for four 21-day cycles

Locations

Country	Name	City	State
Australia	Lyell McEwin Hospital	Adelaide	South Australia
Australia	Pindara Private Hospital	Benowa	Queensland
Australia	Monash Health	Clayton	Victoria
Australia	Barwon Health	Geelong	Victoria
Australia	Westmead Hospital	Westmead	New South Wales
Belgium	UZ Brussel	Brussel
Belgium	GHdC Site Notre Dame	Charleroi
Belgium	Jessa Zkh (Campus Virga Jesse)	Hasselt
Belgium	UZ Leuven Gasthuisberg	Leuven
Belgium	AZ St Maarten Campus Leopoldstr	Mechelen
Brazil	Hospital de Cancer de Barretos	Barretos	SP
Brazil	Crio - Centro Regional Integrado de Oncologia	Fortaleza	CE
Brazil	Hospital de Clínicas de Porto Alegre X	Porto Alegre	RS
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	RS
Brazil	Nucleo de Oncologia da Bahia - NOB	Salvador, Bahia	BA
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
Canada	Lakeridge Health Oshawa	Oshawa	Ontario
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	Windsor Regional Hospital	Windsor	Ontario
France	Hopital Jean Minjoz; Pneumologie	Besancon
France	Centre Leon Berard	Lyon
France	Hopital Cochin; Unite Fonctionnelle D Oncologie	Paris
France	Ico Rene Gauducheau; Oncologie	Saint Herblain
France	Centre Paul Strauss; Oncologie Medicale	Strasbourg
France	CHU de Toulouse - Hôpital Larrey; Service de pneumologie et oncologie pneumologique	Toulouse cedex 9
Germany	Uniklinik Essen	Essen
Germany	LungenClinic Großhansdorf GmbH; Klinische Forschung	Großhansdorf
Germany	Krankenhaus Martha-Maria Halle-Doelau	Halle (Saale)
Germany	Thoraxklinik Heidelberg gGmbH	Heidelberg
Germany	Lungenfachklinik Immenhausen	Immenhausen
Italy	Azienda Ospedaliera San Giuseppe Moscati	Avellino	Campania
Italy	AZ.Osp S. Orsola ? Malpighi-Reparto di Oncologia Medica	Bologna	Emilia-Romagna
Italy	IRCCS AOU San Martino - IST	Genova	Liguria
Italy	Irccs Istituto Europeo di Oncologia (IEO); Divisione di Oncologia	Milano	Lombardia
Italy	Asst Di Monza	Monza	Lombardia
Italy	IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II	Padova	Veneto
Italy	Policlinico Universitario "Agostino Gemelli"; U.O.C. Oncologia Medica	Roma	Lazio
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Mexico	AMIISTO Atencion Medica Integral Investigacion y Terapia Oncologica S.A de C.V	Ciudad de México	Mexico CITY (federal District)
Mexico	ONCARE Viaducto Napoles	Ciudad de México	Mexico CITY (federal District)
Mexico	Instituto Nacional de Cancerologia; Oncology	Mexico City
Mexico	Oncológico Potosino	San Luis Potosí
Spain	Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Oncologia	A Coruña	LA Coruña
Spain	Hospital Universitari Vall d'Hebron; Oncology	Barcelona
Spain	Institut Catala d Oncologia Hospitalet	Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital Regional Universitario Carlos Haya; Servicio de Oncologia	Malaga
Spain	Hospital Son Llatzer	Palma de Mallorca	Islas Baleares
Turkey	Ankara City Hospital; Oncology	Ankara
Turkey	Memorial Ankara Hastanesi	Ankara
Turkey	Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi	Edirne
Turkey	Medipol University Medical Faculty; Oncology Department	Istanbul
Turkey	?zmir Medical Park; Onkoloji	Izmir
United States	Cooper Health System; MD Anderson Cancer Center	Camden	New Jersey
United States	Henry Ford Health System; Hematology/Oncology	Detroit	Michigan
United States	Mitchell Cancer Institute; Pharmacy	Mobile	Alabama
United States	Renown Regional Medical Center Hospital	Reno	Nevada
United States	Virginia Commonwealth University Medical Center Main Hospital	Richmond	Virginia
United States	Avera Cancer Institute	Sioux Falls	South Dakota

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  France,  Germany,  Italy,  Korea, Republic of,  Mexico,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	Overall survival (OS)		From randomization to death from any cause (up to 58 months)
Secondary	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)
Secondary	PFS in participants with PD-L1 expression		Up to 58 months
Secondary	OS for participants with PD-L1 expression		Up to 58 months
Secondary	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
Secondary	Percentage of participants with adverse events (AEs)		Up to 58 months
Secondary	Maximum serum concentration (Cmax) of Tobemstomig		Up to 58 months
Secondary	Time of maximum concentration (Tmax) of Tobemstomig		Up to 58 months
Secondary	Clearance (CL) of Tobemstomig		Up to 58 months
Secondary	Volume of distribution at steady state (Vss) of Tobemstomig		Up to 58 months
Secondary	Area under the concentration-time curve (AUC) of Tobemstomig		Up to 58 months
Secondary	Half-life (T1/2) of Tobemstomig		Up to 58 months
Secondary	Plasma concentration of Carboplatin		Up to 58 weeks
Secondary	Plasma concentration of pemetrexed		Up to 58 months
Secondary	Plasma concentration of paclitaxel		Up to 58 months
Secondary	Percentage of participants with anti-drug antibodies (ADAs)		Baseline up to 58 months