A Study to Evaluate Effects of RO7121661 and RO7247669 Compared With Nivolumab in Advanced or Metastatic Squamous Cell Carcinoma of the Esophagus.

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

14 Apr 2021 → 31 Jan 2025

Decision date (initial)

2024-10-31

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche Ltd

External identifiers

EU CT number

2024-511403-41-00

EudraCT number

2020-004606-60

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacokinetic, Pharmacodynamic, Efficacy, Safety

To evaluate the efficacy of RO7247669 compared with nivolumab based on overall survival

Secondary objectives 6

1. To evaluate the safety and tolerability of RO7121661 and RO7247669 compared with nivolumab
2. To evaluate the efficacy of RO7247669 compared with nivolumab based on objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) and proportion of participants reporting clinically meaningful improvement in global health status/quality of life, emotional functioning, social functioning and dysphagia
3. To investigate the pharmacokinetics (PK) of RO7247669, and nivolumab
4. To evaluate the immune response after administration of RO7247669, and nivolumab
5. To assess treatment-induced pharmacodynamic (PD) changes (PD Biomarkers) in peripheral blood and tumor microenvironment
6. To assess baseline characteristics in the tumor microenvironment as predictive biomarkers of response

Conditions and MedDRA coding

Advanced or metastatic squamous cell carcinoma of the esophagus

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Radiologically measurable disease according to Response evaluation criteria in solid tumors version 1.1 (RECIST v1.1). Previously irradiated lesions should not be counted as target lesions unless clearly progressed after the radiotherapy
2. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
3. AEs from any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade <=1, except alopecia (any grade), vitiligo, endocrinopathy managed with replacement therapy, and Grade 2 peripheral neuropathy
4. Adequate hematological function
5. Adequate liver function
6. Adequate renal function

Exclusion criteria 6

1. Pregnancy, lactation, or breastfeeding
2. Patients with significant malnutrition. Patients whose nutrition has been well controlled for ≥28 days prior to randomization may be enrolled
3. Active or history of carcinomatous meningitis/leptomeningeal disease
4. Uncontrolled tumor-related pain. Participants requiring pain medication must be on a stable regimen at study entry.
5. Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent.
6. Known clinically significant liver disease, including alcoholic hepatitis, cirrhosis, and inherited liver disease

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Overall survival

Secondary endpoints 17

1. 1. Frequency, and severity of adverse events (AEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0)
2. 2. ORR, defined as the proportion of participants with an objective response (i.e., complete response [CR] or partial response [PR]), according to RECIST v1.1
3. 3. DCR defined as ORR plus stable disease rate (SDR)
4. 4. DoR for participants with ORR, defined as the time from the first occurrence of a documented objective response to disease progression according to RECIST v1.1 or death from any cause, whichever occurs first
5. 5. PFS defined as the time from randomization to the first occurrence of progression as determined according to RECIST v1.1 or death during the treatment period or within 60 days of the last tumor assessment after treatment discontinuation from any cause, whichever occurs first
6. 6. Percentage of participants reporting clinically meaningful improvement in global health status/quality of life, emotional functioning, social functioning and dysphagia as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of life questionnaire (QLQ)-C30, defined as an improvement of at least 10 points
7. 7. Percentage of participants reporting clinically meaningful improvement in global health status/quality of life, emotional functioning, social functioning and dysphagia as measured by the EORTC-QLQ-IL97, defined as an improvement of at least 10 points
8. 8. Percentage of participants reporting clinically meaningful improvement in global health status/quality of life, emotional functioning, social functioning and dysphagia as measured by the EORTC-QLQ-OES-18, defined as an improvement of at least 10 points
9. 9. Serum concentrations of RO7121661
10. 10. Serum concentrations of RO7247669
11. 11. Serum concentrations of nivolumab
12. 12. Incidence and titer of anti-drug antibodies (ADAs) against RO7121661 during the study relative to the prevalence of ADAs at baseline
13. 13. Incidence and titer of ADAs against RO7247669 during the study relative to the prevalence of ADAs at baseline
14. 14. Incidence and titer of ADAs against nivolumab during the study relative to the prevalence of ADAs at baseline
15. 15. Changes from baseline in the phenotype and activation status (CD4/CD8 HLA-DR+Ki67+) of T cell subsets in the peripheral blood
16. 16. Changes from baseline such as CD8 T cell infiltration, proliferation (CD8+Ki67+) in the tumor microenvironment
17. 17. Baseline PDL1, CD8+PD1+, CD8+TIM3+, and CD8+LAG3+ expression in the tumor microenvironment

Investigational products

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

Test 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 System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 11

Locations

6 EU/EEA countries · 14 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

Summary of results Art. 37(4) CTR

Documents 50 files

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

Application history

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