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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Mar 2023 → ongoing

Decision date (initial)

2024-03-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann La Roche

External identifiers

EU CT number

2023-505211-21-00

EudraCT number

2022-001440-18

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Others, Pharmacokinetic

To evaluate the efficacy of tobemstomig in combination with platinum‑based chemotherapy (Arm A) compared with pembrolizumab plus platinum‑based chemotherapy (Arm B) on the basis of progression‑free survival (PFS) after randomization and objective response rate (ORR)

Secondary objectives 4

1. To evaluate the efficacy of Arm A compared with Arm B on the basis of overall survival (OS) after randomization, duration of response for participants with confirmed objective response, PFS and OS in participants by programmed death-ligand 1 (PD-L1) expression groups and the change from baseline to Week 12 in patient-reported outcomes of lung cancer symptoms, physical functioning, role functioning, and global health status/quality of life
2. To evaluate the safety of tobemstomig plus platinum‑based chemotherapy (Arm A) compared with pembrolizumab plus platinum‑based chemotherapy (Arm B)
3. To investigate the pharmacokinetics of tobemstomig
4. To evaluate the immune response to tobemstomig on the basis of prevalence of anti-drug antibodies (ADAs) to tobemstomig at baseline and incidence of ADAs to tobemstomig during the study

Conditions and MedDRA coding

Previously untreated locally advanced or metastatic non-small cell lung cancer (NSCLC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
2. 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
3. No prior systemic treatment for metastatic NSCLC
4. Known tumor PD-L1 status
5. Confirmed availability of representative tumor specimens
6. Adequate hematologic and end-organ function

Exclusion criteria 5

1. NSCLC known to have a mutation in the EGFR gene or an ALK fusion oncogene. Known targetable c-ROS oncogene 1 (ROS1), BRAFV600E or RET proto-oncogene genomic aberrations
2. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases. Untreated or clinically unstable spinal cord compression
3. History of leptomeningeal disease
4. Uncontrolled tumor-related pain. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once a month or more frequently)
5. Active or history of autoimmune disease or immune deficiency

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. PFS after randomization, 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 RECIST v1.1
2. 2. ORR, defined as the proportion of participants with a complete response or a partial response on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1

Secondary endpoints 13

1. 1. OS after randomization, defined as the time from randomization to death from any cause
2. 2. Duration of response for participants with confirmed objective response, defined as the time from the first occurrence of a confirmed objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1
3. 3. PFS and OS in participants with PD-L1 expression, defined as tumor cells < 1%, 1%-49%, and < 50%, as assessed by retrospective central PD-L1 testing
4. 4. Change from baseline to Week 12 in patient-reported outcomes of lung cancer symptoms, physical functioning, role functioning, and global health status/quality of life, as assessed through the use of the European Organisation for Research and Treatment of Cancer Item Libraries
5. 5. Incidence and severity of adverse events, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 The severity of cytokine release syndrome will also be determined according to the American Society for Transplantation and Cellular Therapy Consensus Grading Scale.
6. 6. Maximum concentration of tobemstomig
7. 7. Time of maximum concentration of tobemstomig
8. 8. Clearance of tobemstomig
9. 9. Volume of distribution at steady state of tobemstomig
10. 10. Area under the concentration-time curve tobemstomig
11. 11. Half‑life of tobemstomig
12. 12. Concentrations of tobemstomig in serum at specified timepoints
13. 13.Prevalence of ADAs to tobemstomig at baseline and incidence of ADAs to tobemstomig during the study

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information Support Line - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information Support Line - TISL

Third parties 6

Locations

5 EU/EEA countries · 24 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 90 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications