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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05775289

Enrollment

182

Registered

2023-03-20

Start date

2023-03-15

Completion date

2026-04-30

Last updated

2026-07-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Non-small Cell Lung Cancer

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.

Interventions

DRUGTobemstomig

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

DRUGPembrolizumab

Participants will receive IV pembrolizumab four 21-day cycles

DRUGPaclitaxel

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

DRUGPemetrexed

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

DRUGCarboplatin

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Progression-Free Survival (PFS)	Randomization to date of first documented disease progression or death (up to approximately 15 months)	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.
Objective Response Rate (ORR)	Up to approximately 15 months	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.

Secondary

Measure	Time frame	Description
Overall Survival (OS)	From randomization to death from any cause (up to approximately 15 months)	OS is defined as the time from randomization to death from any cause.
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 approximately 15 months)	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.
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	Baseline to week 12	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.
Change in Participant-reported Outcomes as Assessed by the EORTC: Global Health Status/Quality of Life (GHS/QoL)	Baseline to week 12	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.
Change in Participant-reported Outcomes as Assessed by the EORTC: Role Functioning	Baseline to week 12	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.
Change in Participant-reported Outcomes as Assessed by the EORTC: Lung Cancer Symptoms/How Much Did You Cough	Baseline to week 12	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.
Change in Participant-reported Outcomes as Assessed by the EORTC: Short of Breath When Rested	Baseline to week 12	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.
Change in Participant-reported Outcomes as Assessed by the EORTC: Short of Breath When Walked	Baseline to week 12	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.
Change in Participant-reported Outcomes as Assessed by the EORTC: Short of Breath Climbed Stairs	Baseline to week 12	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.
Change in Participant-reported Outcomes as Assessed by the EORTC: Pain in Chest	Baseline to week 12	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.
Change in Participant-reported Outcomes as Assessed by the EORTC: Need to Rest	Baseline to week 12	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.
Change in Participant-reported Outcomes as Assessed by the EORTC: Felt Weak	Baseline to week 12	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.
Change in Participant-reported Outcomes as Assessed by the EORTC: Tired	Baseline to week 12	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.
Change in Participant-reported Outcomes as Assessed by the EORTC: Aches/Pain in Bones	Baseline to week 12	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.
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	—

Countries

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

Contacts

STUDY_DIRECTORClinical Trials

Hoffmann-LaRoche

Participant flow

Recruitment details

Male and female participants ages at least 18 years with previously untreated locally advanced or metastatic non-small cell lung cancer.

Participants by arm

Arm	Count
Pembro + Chemotherapy (Squamous) Participants with squamous non small-cell lung cancer (NSCLC) received blinded pembrolizumab (pembro) in combination with paclitaxel and carboplatin on Day 1 every three weeks (Q3W) for four 21-day cycles, followed by blinded pembro with pemetrexed Q3W until disease progression or treatment discontinuation for a maximum of 24 months of treatment.	25
Pembro + Chemotherapy (Non-squamous) Participants with non-squamous NSCLC received induction treatment with blinded pembro in combination with pemetrexed and carboplatin on Day 1 Q3W for four 21-day cycles, followed by maintenance therapy with blinded pembro with pemetrexed Q3W until disease progression or treatment discontinuation for a maximum of 24 months of treatment.	66
Tobe + Chemotherapy (Squamous) Participants with SQ NSCLC received blinded tobemstomig in combination with paclitaxel and carboplatin on Day 1 Q3W until disease progression or treatment discontinuation for a maximum of 24 months of treatment.	24
Tobe + Chemotherapy (Non-squamous) Participants with NSQ NSCLC received induction treatment with blinded tobemstomig in combination with pemetrexed and carboplatin on Day 1 Q3W for four 21-day cycles, followed by Q3W maintenance therapy with blinded tobemstomig with pemetrexed until disease progression or treatment discontinuation for a maximum of 24 months of treatment.	67
Total	182

Baseline characteristics

Characteristic	Tobe + Chemotherapy (Non-squamous)	Total	Pembro + Chemotherapy (Squamous)	Pembro + Chemotherapy (Non-squamous)	Tobe + Chemotherapy (Squamous)
Age, Continuous	64.8 Years STANDARD_DEVIATION 8.3	64.2 Years STANDARD_DEVIATION 9	66.2 Years STANDARD_DEVIATION 6.8	63.2 Years STANDARD_DEVIATION 9.6	63.0 Years STANDARD_DEVIATION 11.2
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants	29 Participants	7 Participants	10 Participants	5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	53 Participants	137 Participants	18 Participants	49 Participants	17 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants	16 Participants	0 Participants	7 Participants	2 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	3 Participants	1 Participants	1 Participants	1 Participants
Race (NIH/OMB) Asian	5 Participants	22 Participants	4 Participants	10 Participants	3 Participants
Race (NIH/OMB) Black or African American	0 Participants	5 Participants	0 Participants	5 Participants	0 Participants
Race (NIH/OMB) More than one race	2 Participants	2 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	7 Participants	20 Participants	2 Participants	10 Participants	1 Participants
Race (NIH/OMB) White	53 Participants	130 Participants	18 Participants	40 Participants	19 Participants
Sex: Female, Male Female	24 Participants	64 Participants	5 Participants	27 Participants	8 Participants
Sex: Female, Male Male	43 Participants	118 Participants	20 Participants	39 Participants	16 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	4 / 25	11 / 65	8 / 24	12 / 65
other Total, other adverse events	25 / 25	63 / 65	24 / 24	63 / 65
serious Total, serious adverse events	10 / 25	26 / 65	14 / 24	35 / 65

Outcome results

Primary

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.

Time frame: Up to approximately 15 months

Population: The analysis population was all randomized participants with measurable disease at baseline.

Arm	Measure	Value (NUMBER)
Pembro + Chemotherapy	Objective Response Rate (ORR)	46.2 Percent of participants
Tobe + Chemotherapy	Objective Response Rate (ORR)	41.1 Percent of participants

p-value: 0.405695% CI: [0.42, 1.43]Cochran-Mantel-Haenszel

Primary

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.

Time frame: Randomization to date of first documented disease progression or death (up to approximately 15 months)

Population: The analysis population included all participants that were randomized.

Arm	Measure	Value (MEDIAN)
Pembro + Chemotherapy	Progression-Free Survival (PFS)	7.13 Months
Tobe + Chemotherapy	Progression-Free Survival (PFS)	7.62 Months

p-value: 0.970595% CI: [0.63, 1.56]Log Rank

Secondary

Area Under the Concentration-time Curve (AUC) of Tobemstomig

Time frame: Up to approximately 15 months

Population: The pharmacokinetic (PK) population consisted of participants who received IV tobemstomig.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Tobe + Chemotherapy	Area Under the Concentration-time Curve (AUC) of Tobemstomig	Tobe + Paclitaxel + Carboplatin	1470 day*ug/mL	Geometric Coefficient of Variation 31.8
Tobe + Chemotherapy	Area Under the Concentration-time Curve (AUC) of Tobemstomig	Tobe + Pemetrexed + Carboplatin	1500 day*ug/mL	Geometric Coefficient of Variation 114.2

Secondary

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.