Active, not recruiting
Phase 1/2
Dose Escalation Study of a PD1-LAG3 Bispecific Antibody in Patients With Advanced and/or Metastatic Solid Tumors
Condition(s) studied
Solid TumorsMetastatic MelanomaNon-small Cell Lung CancerEsophageal Squamous Cell Carcinoma
Investigational drug(s) / intervention(s)
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
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 |
Yen?mahalle |
Turkey (Türkiye) |
|
| Queen Elizabeth Hospital |
Birmingham |
United Kingdom |
|
| Christie Hospital NHS Trust |
Manchester |
United Kingdom |
|
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