Dose Escalation Study of a PD1-LAG3 Bispecific Antibody in Patients With Advanced and/or Metastatic Solid Tumors
- Cancer
- Melanoma
- Metastatic Melanoma
- Lung Cancer
- Non-Small Cell Lung Cancer (NSCLC)
- Solid Tumors
- Esophageal Squamous Cell Carcinoma
Recruiting
- Brazil
- Denmark
- Israel
- Moldova
- Singapore
- South Korea
- Spain
- tuerkiye
- United Kingdom
NCT04140500 2019-000779-18 NP41300
Trial 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.
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
Eligibility 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
- 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
For the latest version of this information please go to www.forpatients.roche.com