Dose Escalation Study of a PD1-LAG3 Bispecific Antibody in Patients With Advanced and/or Metastatic Solid Tumors

NCT ID: NCT04140500

Last Updated: 2025-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

170 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-11-11

Study Completion Date

2026-06-30

Brief Summary

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This is a first-in-human, open-label, multicenter, Phase I multiple-ascending dose (MAD) study of RO7247669, an anti PD-1 (programmed death-1) and LAG-3 (Lymphocyte-activation gene 3) bispecific antibody, for participants with advanced and/or metastatic solid tumors. This study aims to establish the maximum tolerated dose (MTD) and/or define the recommended phase 2 dose (RP2D) based on the safety, tolerability, pharmacokinetic (PK) and/or pharmacodynamic (PD) profile of RO7247669, and to evaluate preliminary anti-tumor activity in participants with solid tumors. An expansion part of the study is planned to enroll tumor-specific cohorts to evaluate anti-tumor activity of the MTD and/or RP2D of RO7247669 and to confirm safety and tolerability in participants with selected tumor types.

Detailed Description

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Conditions

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Solid Tumors Metastatic Melanoma Non-small Cell Lung Cancer Esophageal Squamous Cell Carcinoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part A: Single-Agent Dose Escalation

Participants will receive RO7247669 every 2 weeks (Q2W) or every 3 weeks (Q3W) up to the maximum tolerated dose (MTD) until disease progression, unacceptable drug toxicity, or withdrawal of consent, for up to 24 months.

Group Type EXPERIMENTAL

RO7247669

Intervention Type DRUG

Participants will receive intravenous (IV) RO7247669 at different doses either every 2 weeks (Q2W) or every 3 weeks (Q3W)

Part B: Tumor Specific Expansion Cohorts

Participants with selected solid tumor indications will receive RO7247669 at a dose derived from Part A until disease progression, unacceptable drug toxicity, or withdrawal of consent, for up to 24 months.

Group Type EXPERIMENTAL

RO7247669

Intervention Type DRUG

Participants will receive intravenous (IV) RO7247669 at different doses either every 2 weeks (Q2W) or every 3 weeks (Q3W)

Interventions

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RO7247669

Participants will receive intravenous (IV) RO7247669 at different doses either every 2 weeks (Q2W) or every 3 weeks (Q3W)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patient must have histologically or cytologically confirmed advanced and/or metastatic solid tumor malignancies for which standard curative or palliative measures do not exist, are no longer effective, or are not acceptable to the patient
* Eastern Cooperative Oncology Group Performance Status 0-1
* Fresh biopsies may be required
* Women of childbearing potential and male participants must agree to remain abstinent or use contraceptive methods as defined by the protocol


* Histologically confirmed, unresectable stage III or stage IV melanoma
* Not more than 2 prior lines of treatment for metastatic disease are allowed prior to enrolling in the study
* Prior treatment with an approved anti-PD-1 or anti-PD-L1 agent


* Participants with histologically confirmed advanced non-small cell lung cancer
* Not more than 2 prior lines of treatment for metastatic disease are allowed prior to enrolling in the study
* Previously treated with approved PD-L1/PD-1 inhibitors
* Tumor PD-L1 expression as determined by immunohistochemistry assay of archival tumor tissue or tissue obtained at screening


* Participants whose major lesion was histologically confirmed as squamous cell carcinoma or adenosquamous cell carcinoma of the esophagus
* Participants who have previously received not more than 1 prior line of treatment for metastatic disease prior to enrolling in the study


* Participants with histologically confirmed advanced non-small cell lung cancer
* Tumor PD-L1 expression as determined by immunohistochemistry assay of archival tumor tissue or tissue obtained at screening

Exclusion Criteria

* Pregnancy, lactation, or breastfeeding
* Known hypersensitivity to any of the components of RO7247669
* Active or untreated central nervous system (CNS) metastases
* An active second malignancy
* Evidence of concomitant 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
* Positive HIV, hepatitis B, or hepatitis C test result
* Known active or uncontrolled bacterial, viral, fungal, mycobacterial, parasitic, or other infection
* Vaccination with live vaccines within 28 days prior to Cycle 1 Day 1
* Treatment with oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1
* Active or history of autoimmune disease or immune deficiency
* Prior treatment with adoptive cell therapies, such as CAR-T therapies
* Concurrent therapy with any other investigational drug \< 28 days or 5 half-lives of the drug, whichever is shorter, prior to the first RO7247669 administration
* Regular immunosuppressive therapy
* Radiotherapy within the last 4 weeks before start of study drug treatment, with the exception of limited palliative radiotherapy
* Prior treatment with a lymphocyte activation gene-3 (LAG-3) inhibitor


* Participants with the following muations, rearrangements, translocations are not eligible: EGFR, ALK, ROS1, BRAFV600E, and NTRK


* Prior therapy with any immunomodulatory agents


* Prior therapy for metastatic disease is not permitted
* Neo-adjuvant anti-PD-1 or anti-PD-L1 therapy is not allowed
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Rigshospitalet

København Ø, , Denmark

Site Status

Odense Universitetshospital, Onkologisk Afdeling R

Odense C, , Denmark

Site Status

LLC Arensia Explorer Medicine

Tbilisi, , Georgia

Site Status

Hadassah University Hospital - Ein Kerem

Jerusaelm, , Israel

Site Status

Rabin MC

Petah Tikva, , Israel

Site Status

Chaim Sheba medical center, Oncology division

Ramat Gan, , Israel

Site Status

Hospital Civil de Guadalajara Fray Antonio Alcalde

Guadalajara, Jalisco, Mexico

Site Status

Inst. Nacional de Cancerología

Mexico City, Mexico CITY (federal District), Mexico

Site Status

Consultorio Médico Jordi Guzmán Casta

Querétaro City, Querétaro, Mexico

Site Status

National University Hospital

Singapore, , Singapore

Site Status

National Cancer Centre

Singapore, , Singapore

Site Status

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Site Status

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Clinica Universitaria de Navarra

Pamplona, Navarre, Spain

Site Status

Vall d?Hebron Institute of Oncology (VHIO), Barcelona

Barcelona, , Spain

Site Status

Clinica Universidad de Navarra Madrid

Madrid, , Spain

Site Status

START Madrid-FJD, Hospital Fundacion Jimenez Diaz

Madrid, , Spain

Site Status

START Madrid. Centro Integral Oncologico Clara Campal

Madrid, , Spain

Site Status

Adana City Hospital, Medical Oncology

Adana, , Turkey (Türkiye)

Site Status

Ankara City Hospital

Ankara, , Turkey (Türkiye)

Site Status

Hacettepe Uni Medical Faculty Hospital

Sihhiye/Ankara, , Turkey (Türkiye)

Site Status

Ankara Abdurrahman Yurtaslan Oncology Training and Research Hospital Phase 1 Center

Yen?mahalle, , Turkey (Türkiye)

Site Status

Queen Elizabeth Hospital

Birmingham, , United Kingdom

Site Status

Christie Hospital NHS Trust

Manchester, , United Kingdom

Site Status

Countries

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Brazil Moldova Portugal United States Denmark Georgia Israel Mexico Singapore South Korea Spain Turkey (Türkiye) United Kingdom

Other Identifiers

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2019-000779-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NP41300

Identifier Type: -

Identifier Source: org_study_id