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

Roche

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Non-small Cell Lung Cancer; Metastatic Melanoma; Esophageal Squamous Cell Carcinoma; Solid Tumors

Treatments: Drug: RO7247669

Study type: Interventional

Funder types: Industry

Identifiers

NCT04140500

2019-000779-18 (EudraCT Number)

NP41300

Details and patient eligibility

About

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.

Enrollment: 170 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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170 participants in 2 patient groups

Part A: Single-Agent Dose Escalation

Experimental group

Description:

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.

Treatment:

Drug: RO7247669

Part B: Tumor Specific Expansion Cohorts

Experimental group

Description:

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.

Treatment:

Drug: RO7247669