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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
170
Participants will receive intravenous (IV) RO7247669 at different doses either every 2 weeks (Q2W) or every 3 weeks (Q3W)
Rigshospitalet
København Ø, Denmark
Odense Universitetshospital, Onkologisk Afdeling R
Odense C, Denmark
LLC Arensia Explorer Medicine
Tbilisi, Georgia
Hadassah University Hospital - Ein Kerem
Jerusaelm, Israel
Rabin MC
Petah Tikva, Israel
Chaim Sheba medical center, Oncology division
Ramat Gan, Israel
Hospital Civil de Guadalajara Fray Antonio Alcalde
Guadalajara, Jalisco, Mexico
Inst. Nacional de Cancerología
Mexico City, Mexico CITY (federal District), Mexico
Consultorio Médico Jordi Guzmán Casta
Querétaro City, Querétaro, Mexico
National University Hospital
Singapore, Singapore
...and 15 more locations
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
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)
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