RO7247669: Participants will receive intravenous (IV) RO7247669 at different doses either every 2 weeks (Q2W) or every 3 weeks (Q3W)
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
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 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
Primary outcome measure(s)
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
Trial sites (25)
Facility
City
Region
Status
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
Inst. Nacional de Cancerología
Mexico City
Mexico CITY (federal District)
Consultorio Médico Jordi Guzmán Casta
Querétaro City
Querétaro
National University Hospital
Singapore
Singapore
National Cancer Centre
Singapore
Singapore
Seoul National University Bundang Hospital
Seongnam-si
South Korea
Severance Hospital, Yonsei University Health System
Seoul
South Korea
Asan Medical Center
Seoul
South Korea
Clinica Universitaria de Navarra
Pamplona
Navarre
Vall d?Hebron Institute of Oncology (VHIO), Barcelona
Barcelona
Spain
Clinica Universidad de Navarra Madrid
Madrid
Spain
START Madrid-FJD, Hospital Fundacion Jimenez Diaz
Madrid
Spain
START Madrid. Centro Integral Oncologico Clara Campal
Madrid
Spain
Adana City Hospital, Medical Oncology
Adana
Turkey (Türkiye)
Ankara City Hospital
Ankara
Turkey (Türkiye)
Hacettepe Uni Medical Faculty Hospital
Sihhiye/Ankara
Turkey (Türkiye)
Ankara Abdurrahman Yurtaslan Oncology Training and Research Hospital Phase 1 Center
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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