Dose Escalation Study of a PD1-LAG3 Bispecific Antibody in Patients With Advanced and/or Metastatic Solid Tumors
- Conditions
- Metastatic MelanomaNon-small Cell Lung CancerSolid TumorsEsophageal Squamous Cell Carcinoma
- Interventions
- Registration Number
- NCT04140500
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 170
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Part B: Tumor Specific Expansion Cohorts RO7247669 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. Part A: Single-Agent Dose Escalation RO7247669 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.
- Primary Outcome Measures
Name Time Method 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: Duration of Response (DOR) Up to 24 months Part B: Disease Control Rate (DCR), Defined as ORR + Stable Disease Rate (SDR) 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 Part B: Objective Response Rate (ORR) Up to 24 months
- Secondary Outcome Measures
Name Time Method 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: 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) 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: DOR At pre-defined intervals from initial dose 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: 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: PFS 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) 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: 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) 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)
Trial Locations
- Locations (26)
START Madrid-FJD, Hospital Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
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
🇮🇱Petach Tikva, Israel
Chaim Sheba medical center, Oncology division
🇮🇱Ramat Gan, Israel
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
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