Solid Tumors, Metastatic Melanoma, Non-small Cell Lung Cancer, Esophageal Squamous Cell Carcinoma
Conditions
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.
Interventions
DRUGRO7247669
Participants will receive intravenous (IV) RO7247669 at different doses either every 2 weeks (Q2W) or every 3 weeks (Q3W)
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: Percentage of Participants with Dose-Limiting Toxicities (DLTs) | Days 1-21 (Q2W dosing) or Days 1-28 (Q3W dosing) of Cycle 1 |
| Part A: Percentage of Participants with Adverse Events | Baseline through the end of study (up to 24 months) |
| Part B: Objective Response Rate (ORR) | Up to 24 months |
| Part B: Disease Control Rate (DCR), Defined as ORR + Stable Disease Rate (SDR) | Up to 24 months |
| Part B: Duration of Response (DOR) | 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 | Up to 24 months |
Secondary
| Measure | Time frame |
|---|---|
| Parts A and B: Maximum Concentration (Cmax) of RO7247669 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months) |
| Part A: ORR | At pre-defined intervals from initial dose up to 24 months |
| Part A: DCR | At pre-defined intervals from initial dose up to 24 months |
| Part A: PFS | At pre-defined intervals from initial dose up to 24 months |
| Part A: DOR | At pre-defined intervals from initial dose up to 24 months |
| Part B: Percentage of Participants with Adverse Events | Baseline through the end of study (up to 24 months) |
Countries
Denmark, Georgia, Israel, Mexico, Singapore, South Korea, Spain, Turkey (Türkiye), United Kingdom
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed