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

An Open Label, Multicenter, Dose Escalation, Phase 1 Study to Evaluate Safety/Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Anti Tumor Activity of RO7247669, a PD1-LAG3 Bispecific Antibody, in Patients With Advanced and/or Metastatic Solid Tumors

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Melanoma; Non-small Cell Lung Cancer; Solid Tumors; Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: RO7247669

• Study Type: Interventional
• Enrollment (Actual): 170
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Denmark
  • København Ø, Denmark, 2100
    • Rigshospitalet
  • Odense C, Denmark, 5000
    • Odense Universitetshospital, Onkologisk Afdeling R
• Georgia
  • Tbilisi, Georgia, 0112
    • LLC Arensia Explorer Medicine
• Israel
  • Jerusaelm, Israel, 9112001
    • Hadassah University Hospital - Ein Kerem
  • Petah Tikva, Israel, 4941492
    • Rabin MC
  • Ramat Gan, Israel, 5262000
    • Chaim Sheba medical center, Oncology division
• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Hospital Civil de Guadalajara Fray Antonio Alcalde
  • Mexico CITY (federal District)
    • Mexico City, Mexico CITY (federal District), Mexico, 14080
      • Inst. Nacional de Cancerologia
  • Querétaro
    • Querétaro City, Querétaro, Mexico, 76226
      • Consultorio Médico Jordi Guzmán Casta
• Singapore
  • Singapore, Singapore, 169610
    • National Cancer Centre
  • Singapore, Singapore, 119228
    • National University Hospital
• South Korea
  • Seongnam-si, South Korea, 13605
    • Seoul National University Bundang Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
• Spain
  • Barcelona, Spain, 08035
    • Vall d?Hebron Institute of Oncology (VHIO), Barcelona
  • Madrid, Spain, 28040
    • START Madrid-FJD, Hospital Fundacion Jimenez Diaz
  • Madrid, Spain, 28050
    • START Madrid. Centro Integral Oncologico Clara Campal
  • Madrid, Spain, 28027
    • Clinica Universidad de Navarra Madrid
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universitaria de Navarra
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01060
    • Adana City Hospital, Medical Oncology
  • Ankara, Turkey (Türkiye), 06800
    • Ankara City Hospital
  • Sihhiye/Ankara, Turkey (Türkiye), 06230
    • Hacettepe Uni Medical Faculty Hospital
  • Yen?mahalle, Turkey (Türkiye), 06200
    • Ankara Abdurrahman Yurtaslan Oncology Training and Research Hospital Phase 1 Center
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Queen Elizabeth Hospital
  • Manchester, United Kingdom, M20 4BX
    • Christie Hospital NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Additional Specific Inclusion Criteria for Participants with Melanoma

• 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

Additional Specific Inclusion Criteria for Participants with Non-Small Cell Lung Cancer who Previously Received Treatment for Metastatic Disease

• 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

Additional Specific Inclusion Criteria for Participants with Esophageal Squamous Cell Carcinoma

• 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

Additional Specific Inclusion Criteria for Participants with Non-Small Cell Lung Cancer who Previously did not Receive Treatment for Metastatic Disease

• 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

Additional Specific Exclusion Criteria for Participants with Non-Small Cell Lung Cancer who Previously Received Treatment for Metastatic Disease

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

Additional Specific Exclusion Criteria for Participants with Esophageal Squamous Cell Carcinoma

• Prior therapy with any immunomodulatory agents

Additional Specific Exclusion Criteria for Participants with Non-Small Cell Lung Cancer who Previously did not Receive Treatment for Metastatic Disease

• Prior therapy for metastatic disease is not permitted
• Neo-adjuvant anti-PD-1 or anti-PD-L1 therapy is not allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: RO7247669; Participants will receive intravenous (IV) RO7247669 at different doses either every 2 weeks (Q2W) or every 3 weeks (Q3W)
Experimental: 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.	Drug: RO7247669; Participants will receive intravenous (IV) RO7247669 at different doses either every 2 weeks (Q2W) or every 3 weeks (Q3W)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part A: Percentage of Participants with Dose-Limiting Toxicities (DLTs)	Days 1-21 (Q2W dosing) or Days 1-28 (Q3W dosing) of Cycle 1
Part A: Percentage of Participants with Adverse Events	Baseline through the end of study (up to 24 months)
Part B: Objective Response Rate (ORR)	Up to 24 months
Part B: Disease Control Rate (DCR), Defined as ORR + Stable Disease Rate (SDR)	Up to 24 months
Part B: Duration of Response (DOR)	Up to 24 months
Part B: Progression-free Survival (PFS), Defined as the Time from the First Study Treatment to the First Occurrence of Progression per Investigator Assessment or Death from any Cause, Whichever Occurs First	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Parts A and B: Maximum Concentration (Cmax) of RO7247669	At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months)
Parts A and B: Time of Maximum Concentration (Tmax) of RO7247669	At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months)
Parts A and B: Clearance (CL) of RO7247669	At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months)
Parts A and B: Volume of Distribution at Steady State (Vss) of RO7247669	At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months)
Parts A and B: Area Under the Curve (AUC) of RO7247669	At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months)
Parts A and B: Half-Life (T1/2) of RO7247669	At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months)
Parts A and B: Percentage of Participants with Anti-Drug Antibodies (ADA) to RO7247669	Day 1 of each Cycle, starting with Cycle 1, through final study visit (up to 24 months)
Part B: Change from Baseline in T-Cell Activity	At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months)
Part A: Percentage of Receptors Occupied by RO7247669	At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months)
Part A: ORR	At pre-defined intervals from initial dose up to 24 months
Part A: DCR	At pre-defined intervals from initial dose up to 24 months
Part A: PFS	At pre-defined intervals from initial dose up to 24 months
Part A: DOR	At pre-defined intervals from initial dose up to 24 months
Part B: Percentage of Participants with Adverse Events	Baseline through the end of study (up to 24 months)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2019
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: October 24, 2019
• First Submitted That Met QC Criteria: October 24, 2019
• First Posted (Actual): October 28, 2019

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Lung Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Esophageal Diseases; Lung Neoplasms; Skin Diseases; Carcinoma; Neoplasms, Squamous Cell; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Carcinoma, Squamous Cell; Esophageal Neoplasms; Skin and Connective Tissue Diseases; Esophageal Squamous Cell Carcinoma; Carcinoma, Non-Small-Cell Lung; Melanoma
• Other Study ID Numbers: NP41300; 2019-000779-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No