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

NCT04785820 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: BP427722020-004606-602024-511403-41-00
• Study Type: interventional
• Target: 190
• Locations: 18 countries
• Sites: 52

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

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  OS was defined as the time from randomization to death from any cause. Kaplan-Meier (K-M) method was used to estimate median OS. 80% confidence interval (CI) for median was computed using the method of Brookmeyer and Crowley. IxRS=Interactive response system.

  From randomization to death (up to approximately 38.7 months)

Secondary Outcomes (36)

• Number of Participants With Adverse Events (AEs)

  Up to approximately 27 months

• Objective Response Rate (ORR)

  Up to approximately 38.7months

• Disease Control Rate (DCR)

  Up to approximately 38.7 months

• Duration of Response (DoR)

  Up to approximately 38.7 months

• Progression-free Survival (PFS)

  Up to approximately 38.7 months

Study Arms (3)

Lomvastomig

EXPERIMENTAL

Drug: Lomvastomig

Tobemstomig

EXPERIMENTAL

Drug: Tobemstomig

Nivolumab

ACTIVE COMPARATOR

Drug: Nivolumab

Interventions

Lomvastomig DRUG

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

Also known as: RO7121661, RG7769, PD1-TIM3 BsAb

Lomvastomig

Tobemstomig DRUG

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

Also known as: RO7247669, RG6139, PD1-LAG3 BsAb

Tobemstomig

Nivolumab DRUG

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

Also known as: Opdivo®

Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (52)

Inst. Alexander Fleming

Buenos Aires, C1426ANZ, Argentina

Location

Centro Oncologico Riojano Integral (CORI)

La Rioja, F5300COE, Argentina

Location

Hospital das Clinicas - UFRGS

Porto Alegre, Rio Grande do Sul, Brazil

Location

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, 01246-000, Brazil

Location

Masaryk?v onkologický ústav

Brno, 656 53, Czechia

Location

Fakultni nemocnice Olomouc

Olomouc, 779 00, Czechia

Location

Rigshospitalet

København Ø, 2100, Denmark

Location

Odense Universitetshospital, Onkologisk Afdeling R

Odense C, 5000, Denmark

Location

Hopital Claude Huriez

Lille, 59037, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Hopital Timone Adultes

Marseille, 13385, France

Location

Institut régional du Cancer Montpellier

Montpellier, 34298, France

Location

APHP - Hopital Saint Antoine

Paris, 75571, France

Location

ICO Rene Gauducheau

Saint-Herblain, 44805, France

Location

Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet

Szolnok, 5004, Hungary

Location

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

Meldola, Emilia-Romagna, 47014, Italy

Location

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

Udine, Friuli Venezia Giulia, 33100, Italy

Location

IRCCS Istituto Oncologico Veneto (IOV)

Padua, Veneto, 35128, Italy

Location

International Cancer Institute (ICI)

Eldoret, 30100, Kenya

Location

The Aga Khan University-Kenya.

Nairobi, 00100, Kenya

Location

Centrum Onkologii w Bydgoszczy

Bydgoszcz, 85-796, Poland

Location

Szpital Morski im. PCK

Gdynia, 81-519, Poland

Location

Krakowski Szpital Specjalistyczny im sw. Jana Paw?a II

Krakow, 31-202, Poland

Location

NIO im Marii Sklodowskiej-Curie

Warsaw, 02-034, Poland

Location

Bashkirian Republican Clinical Oncology Dispensary

Ufa, Bashkortostan Republic, 450054, Russia

Location

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

Moscow, Moscow Oblast, 119991, Russia

Location

MEDSI Clinical Hospital on Pyatnitsky Highway

Moscow, Moscow Oblast, 143422, Russia

Location

Group of companies "Medci"

Moskva, Moscow Oblast, 105229, Russia

Location

National Cancer Centre

Singapore, 168583, Singapore

Location

Curie Oncology

Singapore, 329563, Singapore

Location

Chonnam National University Hwasun Hospital

Jeollanam-do, 58128, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, 13605, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Complejo Hospitalario de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Clínic i Provincial

Barcelona, 08036, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Changhua Christian Hospital

Chang-hua, 500, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112201, Taiwan

Location

National Taiwan University Hospital

Zhongzheng Dist., 10048, Taiwan

Location

Ramathibodi Hospital

Bangkok, 10400, Thailand

Location

Siriraj Hospital

Bangkok, 10700, Thailand

Location

Songklanagarind Hospital

Songkhla, 90110, Thailand

Location

Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital

Adana, 01230, Turkey (Türkiye)

Location

Dicle Uni Medical Faculty

Diyarbakır, 10000, Turkey (Türkiye)

Location

Ataturk University Medical Faculty Yakutiye Research Hospital Medical Oncology Department

Erzurum, 25240, Turkey (Türkiye)

Location

Ac?badem Altunizade Hastanesi

Istanbul, Turkey (Türkiye)

Location

Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department

Malatya, 44280, Turkey (Türkiye)

Location

Van Yuzuncu Yil University Hospital

Van, Turkey (Türkiye)

Location

Communal Non profit Enterprise Regional Center of Oncology

Kharkiv, Kharkiv Governorate, 61070, Ukraine

Location

Regional Municipal Institution Sumy Regional Clinical Oncology Dispensary

Sumy, 40005, Ukraine

Location

Nottingham City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2021
• First Posted: March 8, 2021
• Study Start: June 25, 2021
• Primary Completion: January 30, 2025
• Study Completion: January 30, 2025
• Last Updated: March 27, 2026
• Results First Posted: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

KE (2); FR (6); KR (4); RU (4); GB (1); BR (2); TH (3); DK (2); HU (1); CZ (2); AR (2); TW (3); TU (6); IT (3); ES (3); PL (4); UA (2); SG (2)