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

Non-small Cell Lung Cancer Clinical Trial

Official title:

An Open Label, Multicenter, Dose Escalation, Phase 1 Study to Evaluate Safety/Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Anti Tumor Activity of RO7247669, a PD1-LAG3 Bispecific Antibody, in Patients With Advanced and/or Metastatic Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04140500
• Other study ID #: NP41300
• Secondary ID: 2019-000779-18
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 11, 2019
• Est. completion date: December 31, 2025

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID: NP41300 https://forpatients.roche.com/
• Phone: 888-662-6728 (U.S. and Canada)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 320
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
Brazil	Hospital de Clinicas de Porto Alegre X; Centro de Pesquisa Clinica	Porto Alegre	RS
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
Denmark	Rigshospitalet; Fase 1 Enhed - Onkologi	København Ø
Denmark	Odense Universitetshospital, Onkologisk Afdeling R	Odense C
Georgia	LLC Arensia Explorer Medicine	Tbilisi
Israel	Hadassah University Hospital - Ein Kerem; Oncology	Jerusalem
Israel	Rabin MC; Davidof Center - Oncology Institute	Petach Tikva
Israel	Chaim Sheba medical center, Oncology division	Ramat Gan
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Mexico	Hospital Civil de Guadalajara Fray Antonio Alcalde	Guadalajara	Jalisco
Mexico	Inst. Nacional de Cancerología; Pneumology	Mexico City	Mexico CITY (federal District)
Mexico	Consultorio Médico Jordi Guzmán Casta	Querétaro	Queretaro
Moldova, Republic of	The Institute of Oncology, ARENSIA Exploratory Medicine	Chisinau
Portugal	IPO do Porto; Servico de Oncologia Medica	Porto
Singapore	National Cancer Centre; Medical Oncology	Singapore
Singapore	National University Hospital; National University Cancer Institute, Singapore (NCIS)	Singapore
Spain	Hospital del Mar; Servicio de Oncologia	Barcelona
Spain	Vall d?Hebron Institute of Oncology (VHIO), Barcelona	Barcelona
Spain	Clinica Universidad de Navarra Madrid; Servicio de Oncología	Madrid
Spain	START Madrid-FJD, Hospital Fundacion Jimenez Diaz	Madrid
Spain	START Madrid. Centro Integral Oncologico Clara Campal; CIOCC	Madrid
Spain	Clinica Universitaria de Navarra; Servicio de Oncologia	Pamplona	Navarra
Turkey	Adana City Hospital, Medical Oncology	Adana
Turkey	Ankara City Hospital; Oncology	Ankara
Turkey	Koc University Hospital; Oncology	Istanbul
Turkey	Hacettepe Uni Medical Faculty Hospital; Oncology Dept	Sihhiye/Ankara
Turkey	Ankara Abdurrahman Yurtaslan Oncology Training and Research Hospital Phase 1 Center	Yen?mahalle
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	Christie Hospital NHS Trust; Experimental Cancer Medicine Team	Manchester
United States	Henry Ford Hospital; Hematology/Oncology Phase 1	Detroit	Michigan
United States	Sharp Memorial Hospital	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Brazil,  Denmark,  Georgia,  Israel,  Korea, Republic of,  Mexico,  Moldova, Republic of,  Portugal,  Singapore,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Percentage of Participants with Dose-Limiting Toxicities (DLTs)		Days 1-21 (Q2W dosing) or Days 1-28 (Q3W dosing) of Cycle 1
Primary	Part A: Percentage of Participants with Adverse Events		Baseline through the end of study (up to 24 months)
Primary	Part B: Objective Response Rate (ORR)		Up to 24 months
Primary	Part B: Disease Control Rate (DCR), Defined as ORR + Stable Disease Rate (SDR)		Up to 24 months
Primary	Part B: Duration of Response (DOR)		Up to 24 months
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Part A: ORR		At pre-defined intervals from initial dose up to 24 months
Secondary	Part A: DCR		At pre-defined intervals from initial dose up to 24 months
Secondary	Part A: PFS		At pre-defined intervals from initial dose up to 24 months
Secondary	Part A: DOR		At pre-defined intervals from initial dose up to 24 months
Secondary	Part B: Percentage of Participants with Adverse Events		Baseline through the end of study (up to 24 months)