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

NCT04140500 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: NP413002019-000779-18
• Study Type: interventional
• Target: 170
• Locations: 9 countries
• Sites: 25

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.

Conditions

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

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (14)

• 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)

Study Arms (2)

Part A: Single-Agent Dose Escalation

EXPERIMENTAL

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.

Drug: RO7247669

Part B: Tumor Specific Expansion Cohorts

EXPERIMENTAL

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.

Drug: RO7247669

Interventions

RO7247669 DRUG

Participants will receive intravenous (IV) RO7247669 at different doses either every 2 weeks (Q2W) or every 3 weeks (Q3W)

Part A: Single-Agent Dose Escalation; Part B: Tumor Specific Expansion Cohorts

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• 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
• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (25)

Rigshospitalet

København Ø, 2100, Denmark

Location

Odense Universitetshospital, Onkologisk Afdeling R

Odense C, 5000, Denmark

Location

LLC Arensia Explorer Medicine

Tbilisi, 0112, Georgia

Location

Hadassah University Hospital - Ein Kerem

Jerusaelm, 9112001, Israel

Location

Rabin MC

Petah Tikva, 4941492, Israel

Location

Chaim Sheba medical center, Oncology division

Ramat Gan, 5262000, Israel

Location

Hospital Civil de Guadalajara Fray Antonio Alcalde

Guadalajara, Jalisco, 44280, Mexico

Location

Inst. Nacional de Cancerología

Mexico City, Mexico CITY (federal District), 14080, Mexico

Location

Consultorio Médico Jordi Guzmán Casta

Querétaro City, Querétaro, 76226, Mexico

Location

National University Hospital

Singapore, 119228, Singapore

Location

National Cancer Centre

Singapore, 169610, Singapore

Location

Seoul National University Bundang Hospital

Seongnam-si, 13605, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Clinica Universitaria de Navarra

Pamplona, Navarre, 31008, Spain

Location

Vall d?Hebron Institute of Oncology (VHIO), Barcelona

Barcelona, 08035, Spain

Location

Clinica Universidad de Navarra Madrid

Madrid, 28027, Spain

Location

START Madrid-FJD, Hospital Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

START Madrid. Centro Integral Oncologico Clara Campal

Madrid, 28050, Spain

Location

Adana City Hospital, Medical Oncology

Adana, 01060, Turkey (Türkiye)

Location

Ankara City Hospital

Ankara, 06800, Turkey (Türkiye)

Location

Hacettepe Uni Medical Faculty Hospital

Sihhiye/Ankara, 06230, Turkey (Türkiye)

Location

Ankara Abdurrahman Yurtaslan Oncology Training and Research Hospital Phase 1 Center

Yen?mahalle, 06200, Turkey (Türkiye)

Location

Queen Elizabeth Hospital

Birmingham, B15 2TH, United Kingdom

Location

Christie Hospital NHS Trust

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Melanoma; Carcinoma, Non-Small-Cell Lung; Esophageal Squamous Cell Carcinoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2019
• First Posted: October 28, 2019
• Study Start: November 11, 2019
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

DK (2); KR (3); ES (5); ME (3); GE (1); TU (4); GB (2); IL (3); SG (2)