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Trial record 1 of 1 for:    NP41300
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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 : May 14, 2024
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE October 24, 2019
First Posted Date  ICMJE October 28, 2019
Last Update Posted Date May 14, 2024
Actual Study Start Date  ICMJE November 11, 2019
Estimated Primary Completion Date December 31, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 24, 2020)
  • 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 ]
  • Part A: Percentage of Participants with Adverse Events [ Time Frame: Baseline through the end of study (up to 24 months) ]
  • Part B: Objective Response Rate (ORR) [ Time Frame: Up to 24 months ]
  • Part B: Disease Control Rate (DCR), Defined as ORR + Stable Disease Rate (SDR) [ Time Frame: Up to 24 months ]
  • Part B: Duration of Response (DOR) [ Time Frame: 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 24, 2019)
  • Percentage of Participants with Dose-Limiting Toxicities (DLTs) [ Time Frame: Days 1-21 (Q2W dosing) or Days 1-28 (Q3W dosing) of Cycle 1 ]
  • Percentage of Participants with Adverse Events [ Time Frame: Baseline through the end of study (up to 24 months) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 24, 2020)
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • Part A: ORR [ Time Frame: 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 ]
  • Part A: PFS [ Time Frame: 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 ]
  • Part B: Percentage of Participants with Adverse Events [ Time Frame: Baseline through the end of study (up to 24 months) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2019)
  • 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) ]
  • 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) ]
  • Clearance (CL) of RO7247669 [ Time Frame: At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [ Time Frame: At pre-defined intervals from initial dose up to 24 months ]
  • Disease Control Rate (DCR) According to RECIST v1.1 [ Time Frame: At pre-defined intervals from initial dose up to 24 months ]
  • Progression-Free Survival (PFS) According to RECIST v1.1 [ Time Frame: At pre-defined intervals from initial dose up to 24 months ]
  • Duration of Response (DOR) According to RECIST v1.1 [ Time Frame: At pre-defined intervals from initial dose up to 24 months ]
  • Overall Survival (OS) [ Time Frame: At pre-defined intervals from initial dose up to 24 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose Escalation Study of a PD1-LAG3 Bispecific Antibody in Patients With Advanced and/or Metastatic Solid Tumors
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Solid Tumors
  • Metastatic Melanoma
  • Non-small Cell Lung Cancer
  • Esophageal Squamous Cell Carcinoma
Intervention  ICMJE Drug: RO7247669
Participants will receive intravenous (IV) RO7247669 at different doses either every 2 weeks (Q2W) or every 3 weeks (Q3W)
Study Arms  ICMJE
  • 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.
    Intervention: Drug: RO7247669
  • 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.
    Intervention: Drug: RO7247669
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 24, 2020)		 320
Original Estimated Enrollment  ICMJE
 (submitted: October 24, 2019)		 200
Estimated Study Completion Date  ICMJE December 31, 2025
Estimated Primary Completion Date December 31, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Reference Study ID: NP41300 https://forpatients.roche.com/ 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com
Listed Location Countries  ICMJE Brazil,   Denmark,   Georgia,   Israel,   Korea, Republic of,   Mexico,   Moldova, Republic of,   Portugal,   Singapore,   Spain,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04140500
Other Study ID Numbers  ICMJE NP41300
2019-000779-18 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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).
Current Responsible Party Hoffmann-La Roche
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Hoffmann-La Roche
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date May 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP