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

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ClinicalTrials.gov Identifier: NCT04140500
Recruitment Status : Recruiting
First Posted : October 28, 2019
Last Update Posted : April 28, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Solid Tumors Metastatic Melanoma Non-small Cell Lung Cancer Esophageal Squamous Cell Carcinoma Drug: RO7247669 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 320 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : November 11, 2019
Estimated Primary Completion Date : June 14, 2022
Estimated Study Completion Date : June 14, 2022

Resource links provided by the National Library of Medicine


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)




Primary Outcome Measures :
  1. 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 ]
  2. Part A: Percentage of Participants with Adverse Events [ Time Frame: Baseline through the end of study (up to 24 months) ]
  3. Part B: Objective Response Rate (ORR) [ Time Frame: Up to 24 months ]
  4. Part B: Disease Control Rate (DCR), Defined as ORR + Stable Disease Rate (SDR) [ Time Frame: Up to 24 months ]
  5. Part B: Duration of Response (DOR) [ Time Frame: Up to 24 months ]
  6. 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 ]

Secondary Outcome Measures :
  1. 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) ]
  2. 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) ]
  3. 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) ]
  4. 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) ]
  5. 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) ]
  6. 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) ]
  7. 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) ]
  8. 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) ]
  9. 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) ]
  10. Part A: ORR [ Time Frame: At pre-defined intervals from initial dose up to 24 months ]
  11. Part A: DCR [ Time Frame: At pre-defined intervals from initial dose up to 24 months ]
  12. Part A: PFS [ Time Frame: At pre-defined intervals from initial dose up to 24 months ]
  13. Part A: DOR [ Time Frame: At pre-defined intervals from initial dose up to 24 months ]
  14. Part B: Percentage of Participants with Adverse Events [ Time Frame: Baseline through the end of study (up to 24 months) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 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 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
  • Adjuvant anti-PD-1 or anti-PD-L1 therapy is not allowed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04140500


Contacts
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Contact: Reference Study ID: NP41300 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04140500    
Other Study ID Numbers: NP41300
2019-000779-18 ( EudraCT Number )
First Posted: October 28, 2019    Key Record Dates
Last Update Posted: April 28, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Esophageal Squamous Cell Carcinoma
Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type
Carcinoma, Squamous Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases