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

Sponsor: Hoffmann-La Roche

Sponsor score: 40
Inactive

ClinicalTrials ID:NCT04140500

Patient View

This Phase I study evaluates RO7247669, a bispecific antibody, in patients with advanced/metastatic solid tumors. It aims to determine the maximum tolerated dose and assess safety, tolerability, and preliminary anti-tumor activity. Participants receive IV doses every 2 or 3 weeks. Eligibility includes adults with confirmed solid tumors, adequate organ function, and no prior anti-PD-1/LAG-3 therapy.

Patient Parameters

Program Overview

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.

Eligibility 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 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

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