A Dose Escalation and Expansion Study of Lomvastomig, a PD-1/TIM-3 Bispecific Antibody, in Participants With Advanced and/or Metastatic Solid Tumors

NCT ID: NCT03708328

Last Updated: 2025-08-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 134 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-15
• Study Completion Date: 2024-07-09

Brief Summary

This is a first-in-human, open-label, multicenter, Phase I multiple-ascending dose (MAD) study of single agent lomvastomig (RO7121661), an anti PD-1 (programmed death-1) and TIM-3 (T-cell immunoglobulin and mucin domain 3) bispecific antibody, for participants with advanced and/or metastatic solid tumors. The study consists of 2 parts: Dose Escalation (Part A) and Expansion (Parts B1, B2, B3, B4, and B5). The Dose Escalation part will be conducted first to determine the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) based on safety, tolerability, pharmacokinetic, and/or the pharmacodynamic profile of escalating doses of lomvastomig. The Expansion part will enroll tumor-specific cohorts to evaluate anti-tumor activity of the MTD and/or RDE of lomvastomig from Part A (Q2W) and to confirm safety and tolerability in participants with selected tumor types.

Conditions

Solid Tumors; Metastatic Melanoma; Non-small Cell Lung Cancer (NSCLC); Small Cell Lung Cancer (SCLC); Esophageal Squamous Cell Carcinoma (ESCC)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose Escalation Part A: Once Every 2 Weeks (Q2W)

Lomvastomig will be administered in treatment cycles once every 2 weeks (Q2W). Dose escalation will be carried out according to a modified continual reassessment method (mCRM) with escalation with overdose control (EWOC) design.

Group Type: EXPERIMENTAL

Lomvastomig

Intervention Type: DRUG

Lomvastomig will be administered intravenously (IV) with a flat dose on the schedule described for each study arm.

Expansion Part B1: Metastatic Melanoma Cohort

This cohort will comprise participants with checkpoint inhibitor (CPI) experienced, second line and beyond metastatic melanoma. The starting dose of lomvastomig for Expansion will be derived from the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) and the best dosing schedule determined during Dose Escalation.

Group Type: EXPERIMENTAL

Lomvastomig

Intervention Type: DRUG

Lomvastomig will be administered intravenously (IV) with a flat dose on the schedule described for each study arm.

Expansion Part B2: NSCLC Cohort 1

This cohort will comprise participants with CPI and platinum experienced, second or third line PD-L1 positive non-small cell lung cancer (NSCLC). The starting dose of lomvastomig for Expansion will be derived from the MTD/RDE and the best dosing schedule determined during Dose Escalation.

Group Type: EXPERIMENTAL

Lomvastomig

Intervention Type: DRUG

Lomvastomig will be administered intravenously (IV) with a flat dose on the schedule described for each study arm.

Expansion Part B3: NSCLC Cohort 2

This cohort will comprise participants with PD-L1 high, cancer immunotherapy (CIT) naïve first line NSCLC. The starting dose of lomvastomig for Expansion will be derived from the MTD/RDE and the best dosing schedule determined during Dose Escalation.

This cohort was not initiated and no participants were enrolled in it.

Group Type: EXPERIMENTAL

Lomvastomig

Intervention Type: DRUG

Lomvastomig will be administered intravenously (IV) with a flat dose on the schedule described for each study arm.

Expansion Part B4: SCLC Cohort

This cohort will comprise participants with CPI naïve small cell lung cancer (SCLC) with prior failure of, progression on, or intolerance to, standard therapy. The starting dose of lomvastomig for Expansion will be derived from the MTD/RDE and the best dosing schedule determined during Dose Escalation.

Group Type: EXPERIMENTAL

Lomvastomig

Intervention Type: DRUG

Lomvastomig will be administered intravenously (IV) with a flat dose on the schedule described for each study arm.

Expansion Part B5: ESCC Cohort

This cohort will comprise participants with CPI-naïve esophageal squamous cell carcinoma (ESCC). The starting dose of lomvastomig for Expansion will be derived from the MTD/RDE and the best dosing schedule determined during Dose Escalation.

Group Type: EXPERIMENTAL

Lomvastomig

Intervention Type: DRUG

Lomvastomig will be administered intravenously (IV) with a flat dose on the schedule described for each study arm.

Interventions

Lomvastomig

Lomvastomig will be administered intravenously (IV) with a flat dose on the schedule described for each study arm.

Intervention Type: DRUG

Other Intervention Names

RO7121661; RG7769

Eligibility Criteria

Inclusion Criteria

• Part A: 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
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
• Fresh biopsies may be required
• Negative HIV, hepatitis B, or hepatitis C test result
• 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
• Previously treated with approved anti-programmed death-ligand 1 (PD-L1)/anti-programmed death-1 (PD-1) agents with or without approved anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) therapy and up to one additional treatment regimen

• Histologically confirmed advanced NSCLC
• Previously treated with approved PD-L1/PD-1 inhibitors and platinum-based chemotherapy
• Not more than 2 prior lines of treatment for metastatic disease are allowed prior to enrolling to the study
• Participants must have experienced initial clinical benefit (stable disease or better) from most recent checkpoint inhibitor (CPI) therapy
• Tumor PD-L1 expression as determined by immunohistochemistry assay of archival tumor tissue or tissue obtained at screening

• Histologically confirmed advanced NSCLC
• Tumor PD-L1 expression as determined by immunohistochemistry assay of archival tumor tissue or tissue obtained at screening

• Histologically confirmed SCLC
• Participants may have had prior chemotherapy, radiation therapy, or declined approved therapies for SCLC

• Participants whose major lesion was histologically confirmed as squamous cell carcinoma or adenosquamous cell carcinoma of the esophagus
• Patients who have previously received not more than 1 prior line of treatment for metastatic disease prior to enrolling to the study

Exclusion Criteria

• Pregnancy, lactation, or breastfeeding
• Known hypersensitivity to any of the components of RO7121661
• Active or untreated central nervous system (CNS) metastases
• An active second malignancy
• Evidence of concomitant diseases, metabolic dysfunction, physical examination findings, or clinical laboratory findings 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
• Known active or uncontrolled bacterial, viral, fungal, mycobacterial, parasitic, or other infection
• 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 T-cell immunoglobulin and mucin domain-3 (TIM-3) inhibitor

• Patients with the following mutations, rearrangements, translocations are not eligible: epidermal growth factor receptor (EGFR); anaplastic lymphoma kinase (ALK); ROS proto-oncogene 1 (ROS1), BRAFV600E, and neurotrophic receptor tyrosine kinase (NTRK)

• Prior therapy for metastatic disease
• Adjuvant anti-PD-1 or anti-PD-L1 therapy

• Prior therapy with any immune CPIs (such as anti-PD-L1/PD-1, CTLA-4)

• Prior therapy with any immunomodulatory agents

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Columbia Univ Med Ctr

New York, New York, United States

MD Anderson Cancer Center

Houston, Texas, United States

Herlev Hospital

Herlev, , Denmark

Rigshospitalet

København Ø, , Denmark

Institut Bergonie

Bordeaux, , France

Centre Leon Berard

Lyon, , France

CHU Timone

Marseille, , France

ICO Rene Gauducheau

Saint-Herblain, , France

Auckland City Hospital

Auckland, , New Zealand

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Clinica Universitaria de Navarra

Pamplona, Navarre, Spain

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

Barcelona, , Spain

Hospital Ramon y Cajal

Madrid, , Spain

START Madrid-FJD, Hospital Fundacion Jimenez Diaz

Madrid, , Spain

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Countries

United States; Denmark; France; New Zealand; South Korea; Spain

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2018-000982-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NP40435

Identifier Type: -

Identifier Source: org_study_id