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

March 21, 2024 updated by: Hoffmann-La Roche

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

Study Type

Interventional

Enrollment (Estimated)

320

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • RS
      • Porto Alegre, RS, Brazil, 90035-903
        • Recruiting
        • Hospital de Clinicas de Porto Alegre X; Centro de Pesquisa Clinica
    • SP
      • Sao Paulo, SP, Brazil, 01246-000
        • Recruiting
        • Instituto do Cancer do Estado de Sao Paulo - ICESP
      • København Ø, Denmark, 2100
        • Recruiting
        • Rigshospitalet; Fase 1 Enhed - Onkologi
      • Odense C, Denmark, 5000
        • Active, not recruiting
        • Odense Universitetshospital, Onkologisk Afdeling R
      • Tbilisi, Georgia, 0112
        • Recruiting
        • LLC Arensia Explorer Medicine
      • Jerusalem, Israel, 9112001
        • Active, not recruiting
        • Hadassah University Hospital - Ein Kerem; Oncology
      • Petach Tikva, Israel, 4941492
        • Recruiting
        • Rabin MC; Davidof Center - Oncology Institute
      • Ramat Gan, Israel, 5262000
        • Completed
        • Chaim Sheba medical center, Oncology division
      • Seongnam-si, Korea, Republic of, 463-707
        • Completed
        • Seoul National University Bundang Hospital
      • Seoul, Korea, Republic of, 05505
        • Completed
        • Asan Medical Center
      • Seoul, Korea, Republic of, 03080
        • Completed
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 03722
        • Terminated
        • Severance Hospital, Yonsei University Health System
    • Jalisco
      • Guadalajara, Jalisco, Mexico, 44280
        • Recruiting
        • Hospital Civil de Guadalajara Fray Antonio Alcalde
    • Mexico CITY (federal District)
      • Mexico City, Mexico CITY (federal District), Mexico, 14080
        • Recruiting
        • Inst. Nacional de Cancerología; Pneumology
    • Queretaro
      • Querétaro, Queretaro, Mexico, 76226
        • Recruiting
        • Consultorio Médico Jordi Guzmán Casta
      • Chisinau, Moldova, Republic of, MD-2025
        • Recruiting
        • The Institute of Oncology, ARENSIA Exploratory Medicine
      • Porto, Portugal, 4200-072
        • Withdrawn
        • IPO do Porto; Servico de Oncologia Medica
      • Singapore, Singapore, 119228
        • Recruiting
        • National University Hospital; National University Cancer Institute, Singapore (NCIS)
      • Singapore, Singapore, 168583
        • Recruiting
        • National Cancer Centre; Medical Oncology
      • Barcelona, Spain, 08003
        • Recruiting
        • Hospital del Mar; Servicio de Oncologia
      • Barcelona, Spain, 08035
        • Recruiting
        • Vall d?Hebron Institute of Oncology (VHIO), Barcelona
      • Madrid, Spain, 28027
        • Recruiting
        • Clinica Universidad de Navarra Madrid; Servicio de Oncología
      • Madrid, Spain, 28040
        • Recruiting
        • START Madrid-FJD, Hospital Fundacion Jimenez Diaz
      • Madrid, Spain, 28050
        • Recruiting
        • START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Recruiting
        • Clinica Universitaria de Navarra; Servicio de Oncologia
      • Adana, Turkey, 01060
        • Active, not recruiting
        • Adana City Hospital, Medical Oncology
      • Ankara, Turkey, 06800
        • Recruiting
        • Ankara City Hospital; Oncology
      • Istanbul, Turkey
        • Recruiting
        • Koc University Hospital; Oncology
      • Sihhiye/Ankara, Turkey, 06230
        • Recruiting
        • Hacettepe Uni Medical Faculty Hospital; Oncology Dept
      • Birmingham, United Kingdom, B15 2TH
        • Recruiting
        • Queen Elizabeth Hospital
      • Manchester, United Kingdom, M20 4BX
        • Completed
        • Christie Hospital NHS Trust; Experimental Cancer Medicine Team
    • California
      • San Diego, California, United States, 92123
        • Withdrawn
        • Sharp Memorial Hospital
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Withdrawn
        • Henry Ford Hospital; Hematology/Oncology Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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.
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.
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)
Time Frame: Days 1-21 (Q2W dosing) or Days 1-28 (Q3W dosing) of Cycle 1
Days 1-21 (Q2W dosing) or Days 1-28 (Q3W dosing) of Cycle 1
Part A: Percentage of Participants with Adverse Events
Time Frame: Baseline through the end of study (up to 24 months)
Baseline through the end of study (up to 24 months)
Part B: Objective Response Rate (ORR)
Time Frame: Up to 24 months
Up to 24 months
Part B: Disease Control Rate (DCR), Defined as ORR + Stable Disease Rate (SDR)
Time Frame: Up to 24 months
Up to 24 months
Part B: Duration of Response (DOR)
Time Frame: Up to 24 months
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
Time Frame: Up to 24 months
Up to 24 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Parts A and B: Maximum Concentration (Cmax) of RO7247669
Time Frame: At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months)
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
Time Frame: At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months)
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
Time Frame: At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months)
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
Time Frame: At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months)
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
Time Frame: At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months)
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
Time Frame: At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months)
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
Time Frame: Day 1 of each Cycle, starting with Cycle 1, through final study visit (up to 24 months)
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
Time Frame: At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months)
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
Time Frame: At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months)
At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months)
Part A: ORR
Time Frame: At pre-defined intervals from initial dose up to 24 months
At pre-defined intervals from initial dose up to 24 months
Part A: DCR
Time Frame: At pre-defined intervals from initial dose up to 24 months
At pre-defined intervals from initial dose up to 24 months
Part A: PFS
Time Frame: At pre-defined intervals from initial dose up to 24 months
At pre-defined intervals from initial dose up to 24 months
Part A: DOR
Time Frame: At pre-defined intervals from initial dose up to 24 months
At pre-defined intervals from initial dose up to 24 months
Part B: Percentage of Participants with Adverse Events
Time Frame: Baseline through the end of study (up to 24 months)
Baseline through the end of study (up to 24 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 11, 2019

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2025

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 22, 2024

Last Update Submitted That Met QC Criteria

March 21, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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