A Study of Lomvastomig (RO7121661) and Tobemstomig (RO7247669) Compared With Nivolumab in Participants With Advanced or Metastatic Squamous Cell Carcinoma of the Esophagus

NCT ID: NCT04785820

Last Updated: 2025-03-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 206 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-25
• Study Completion Date: 2025-01-30

Brief Summary

This is a Phase II, randomized, blinded, active-controlled, global, multicenter study designed to evaluate the safety and efficacy of lomvastomig and tobemstomig, compared with nivolumab, in patients with advanced or metastatic esophageal squamous-cell carcinoma (ESCC) refractory or intolerant to fluoropyrimidine- or taxane- and platinum-based regimen.

Following approval of the protocol amendment version 3, recruitment into the lomvastomig arm has been stopped. The decision to stop recruitment for lomvastomig was based on strategic considerations and not based on emerging safety and/or efficacy data. The benefit/risk assessment for lomvastomig remains unchanged.

The study was planned to enroll participants randomized in a 1:1:1 ratio to receive lomvastomig, tobemstomig, or nivolumab. With version 3 of the protocol, recruitment into the lomvastomig arm has stopped, and moving forward, participants will be randomized in a 1:1 ratio to receive either tobemstomig or nivolumab.

Conditions

Advanced or Metastatic Esophageal Squamous Cell Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Lomvastomig

Group Type: EXPERIMENTAL

Lomvastomig

Intervention Type: DRUG

2100 milligrams (mg) administered by intravenous (IV) infusion once every 2 weeks on Day 1 of each 14-day cycle.

Tobemstomig

Group Type: EXPERIMENTAL

Tobemstomig

Intervention Type: DRUG

2100 mg administered by IV infusion once every 2 weeks on Day 1 of each 14-day cycle.

Nivolumab

Group Type: ACTIVE_COMPARATOR

Nivolumab

Intervention Type: DRUG

240 mg administered by IV infusion once every 2 weeks on Day 1 of each 14-day cycle.

Interventions

Lomvastomig

2100 milligrams (mg) administered by intravenous (IV) infusion once every 2 weeks on Day 1 of each 14-day cycle.

Intervention Type: DRUG

Tobemstomig

2100 mg administered by IV infusion once every 2 weeks on Day 1 of each 14-day cycle.

Intervention Type: DRUG

Nivolumab

240 mg administered by IV infusion once every 2 weeks on Day 1 of each 14-day cycle.

Intervention Type: DRUG

Other Intervention Names

RO7121661; RG7769; PD1-TIM3 BsAb; RO7247669; RG6139; PD1-LAG3 BsAb; Opdivo®

Eligibility Criteria

Inclusion Criteria

• Advanced or metastatic, histologically confirmed esophageal squamous-cell carcinoma (ESCC)
• Patients who have previously received 1 line of treatment with either a fluoropyrimidine- and platinum- or a taxane- and platinum-based regimen in non-curative intention prior to randomization; or patients who received treatment with a fluoropyrimidine-/taxane- and platinum-based regimen in curative intention and had recurrence or progression within 24 weeks after the last dose of the treatment
• Radiologically measurable disease according to RECIST v1.1. Previously irradiated lesions should not be counted as target lesions unless clearly progressed after the radiotherapy
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• A life expectancy of at least (≥)12 weeks
• Tissue samples must be provided for analysis of anti-programmed death ligand-1 (PD-L1) tumor positivity
• Adverse events 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
• Adequate cardiovascular, hematological, liver, and renal function
• Serum albumin ≥25 grams per liter (g/L),
• For participants not receiving therapeutic anticoagulation: prothrombin time (PT) and activated partial thromboplastin time ≤1.5 times (×) the upper limit of normal (ULN); for participants receiving therapeutic anticoagulation: stable anticoagulant regimen
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, not a woman of childbearing potential (WOCBP), or a WOCBP who agrees to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods during the treatment period and for at least 5 months after the final dose of study drug and have a negative pregnancy test (blood) within the 7 days prior to randomization.
• A male participant must remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures such as a condom plus an additional contraceptive method and refrain from donating sperm during the treatment period and for at least 5 months after the final dose of study drug

Exclusion Criteria

• Pregnancy, lactation, or breastfeeding
• Known hypersensitivity to any of the components of RO7121661, RO7247669, or nivolumab, including but not limited to, hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
• Patients with significant malnutrition. Patients whose nutrition has been well controlled for ≥28 days prior to randomization may be enrolled
• Evidence of complete esophageal obstruction not amenable to treatment
• Higher risk of bleeding or fistula caused by esophageal lesions invading adjacent organs (aorta or tracheobronchial tree). Patients with manageable fistula may be included at the Investigator's discretion.
• Symptomatic central nervous system (CNS) metastases
• Spinal cord compression not definitively treated with surgery and/or radiation or without evidence that disease has been clinically stable for ≥14 days prior to randomization
• Active or history of carcinomatous meningitis/leptomeningeal disease
• Asymptomatic CNS primary tumors or metastases if they have requirement for steroids or enzyme inducing anticonvulsants in the last 28 days prior to randomization
• Uncontrolled tumor-related pain. Participants requiring pain medication must be on a stable regimen at study entry
• Active second malignancy (with some exceptions)
• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders, known autoimmune diseases or immune deficiency, or other diseases with ongoing fibrosis (such as scleroderma, pulmonary fibrosis, emphysema, neurofibromatosis, palmar/plantar fibromatosis, etc.).
• Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent
• Significant cardiovascular/cerebrovascular disease within 6 months prior to randomization
• Known active or uncontrolled bacterial, viral, fungal, mycobacterial (including but not limited to tuberculosis [TB] and typical mycobacterial disease), parasitic, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with intravenous (IV) antibiotics or hospitalization (relating to the completion of the course of antibiotics, except if for tumor fever) within 28 days prior to randomization
• Known clinically significant liver disease, including alcoholic hepatitis, cirrhosis, and inherited liver disease.
• Major surgical procedure or significant traumatic injury (excluding biopsies) within 28 days prior to randomization, or anticipation of the need for major surgery during the course of the study
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk from treatment complications
• Dementia or altered mental status that would prohibit informed consent
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (expected to occur once monthly or more frequently)
• Active or history of autoimmune disease or immune deficiency
• Positive human immunodeficiency virus (HIV) test at screening
• Positive hepatitis B surface antigen (HBsAg) or positive total hepatitis B core antibody (HBcAb) test at screening
• Positive hepatitis C virus (HCV) antibody test at screening
• Prior cancer therapy with any immunomodulatory agents including checkpoint inhibitors (CPIs; such as anti-PDL1/PD1, anti-CTLA-4, anti-LAG3, anti-TIM3)
• Vaccination with live vaccines within 28 days prior to randomization, or anticipation that a live attenuated vaccine will be required during the study
• Treatment with therapeutic oral or IV antibiotics within 14 days prior to randomization
• Concurrent therapy with any other investigational drug (defined as treatment for which there is currently no regulatory authority approved indication) 28 days or 5 half-lives of the drug (whichever is shorter) prior to randomization
• Treatment with immune-modulating and immune suppressive agents/medication 5 half-lives or 28 days (whichever is shorter) prior to randomization
• Regular immunosuppressive therapy (i.e., for organ transplantation, chronic rheumatologic disease)
• Radiotherapy within the last 28 days before start of study drug treatment is not allowed, with the exception of limited palliative radiotherapy
• Prior treatment with adoptive cell therapies, such as chimeric antigen receptor T cells (CAR-T) therapies

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

NIO im Marii Sklodowskiej-Curie

Warsaw, , Poland

Inst. Alexander Fleming

Buenos Aires, , Argentina

Centro Oncologico Riojano Integral (CORI)

La Rioja, , Argentina

Hospital das Clinicas - UFRGS

Porto Alegre, Rio Grande do Sul, Brazil

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, Brazil

Masaryk?v onkologický ústav

Brno, , Czechia

Fakultni nemocnice Olomouc

Olomouc, , Czechia

Rigshospitalet

København Ø, , Denmark

Odense Universitetshospital, Onkologisk Afdeling R

Odense C, , Denmark

Institut Bergonie

Bordeaux, , France

Hopital Claude Huriez

Lille, , France

Centre Leon Berard

Lyon, , France

Hopital Timone Adultes

Marseille, , France

Institut régional du Cancer Montpellier

Montpellier, , France

APHP - Hopital Saint Antoine

Paris, , France

ICO Rene Gauducheau

Saint-Herblain, , France

Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet

Szolnok, , Hungary

Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST - PPDS

Meldola, Emilia-Romagna, Italy

Azienda Sanitaria Universitaria Integrata di Udine - PO Universitario Santa Maria della

Udine, Friuli Venezia Giulia, Italy

IRCCS Istituto Oncologico Veneto (IOV)

Padua, Veneto, Italy

International Cancer Institute (ICI)

Eldoret, , Kenya

Aga Khan University Hospital

Nairobi, , Kenya

Centrum Onkologii w Bydgoszczy

Bydgoszcz, , Poland

Szpital Morski im. PCK

Gdynia, , Poland

Krakowski Szpital Specjalistyczny im sw. Jana Paw?a II

Krakow, , Poland

Bashkirian Republican Clinical Oncology Dispensary

Ufa, Bashkortostan Republic, Russia

First Moscow State Medical University n.a. I.M. Sechenov

Moscow, Moscow Oblast, Russia

MEDSI Clinical Hospital on Pyatnitsky Highway

Moscow, Moscow Oblast, Russia

Group of companies "Medci"

Moskva, Moscow Oblast, Russia

National Cancer Centre

Singapore, , Singapore

Curie Oncology

Singapore, , Singapore

Chonnam National University Hwasun Hospital

Jeollanam-do, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Complejo Hospitalario de Navarra

Pamplona, Navarre, Spain

Hospital Clínic i Provincial

Barcelona, , Spain

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Changhua Christian Hospital

Chang-hua, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

National Taiwan University Hospital

Zhongzheng Dist., , Taiwan

Ramathibodi Hospital

Bangkok, , Thailand

Siriraj Hospital

Bangkok, , Thailand

Songklanagarind Hospital

Songkhla, , Thailand

Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital

Adana, , Turkey (Türkiye)

Memorial Ankara Hastanesi

Ankara, , Turkey (Türkiye)

Dicle Uni Medical Faculty

Diyarbakır, , Turkey (Türkiye)

Ataturk University Medical Faculty Yakutiye Research Hospital Medical Oncology Department

Erzurum, , Turkey (Türkiye)

Ac?badem Altunizade Hastanesi

Istanbul, , Turkey (Türkiye)

Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department

Malatya, , Turkey (Türkiye)

Van Yuzuncu Yil University Hospital

Van, , Turkey (Türkiye)

Communal Non profit Enterprise Regional Center of Oncology

Kharkiv, Kharkiv Governorate, Ukraine

Regional Municipal Institution Sumy Regional Clinical Oncology Dispensary

Sumy, , Ukraine

Nottingham City Hospital

Nottingham, , United Kingdom

Countries

Argentina; Brazil; Czechia; Denmark; France; Hungary; Italy; Kenya; Poland; Russia; Singapore; South Korea; Spain; Taiwan; Thailand; Turkey (Türkiye); Ukraine; United Kingdom

Other Identifiers

2020-004606-60

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BP42772

Identifier Type: -

Identifier Source: org_study_id