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

Completed · Phase 1

Conditions studied: Solid Tumors, Metastatic Melanoma, Non-small Cell Lung Cancer (NSCLC), Small Cell Lung Cancer (SCLC), Esophageal Squamous Cell Carcinoma (ESCC)

In brief

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.

Key facts

Study ID

NCT03708328

Run by

Hoffmann-La Roche

People needed

134

Starts

2018-10-15

Expected to finish

2024-07-09

Last updated by the study team

2025-08-20

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• General 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
• Additional Specific Inclusion Criteria for Participants with Melanoma:
• 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
• Additional Specific Inclusion Criteria for Participants with Non-small Cell Lung Cancer (NSCLC) who Previously Received Treatment for Metastatic Disease:
• 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
• Additional Specific Inclusion Criteria for Participants with Non-small Cell Lung Cancer (NSCLC) who Previously Did Not Receive Treatment for Metastatic Disease:
• Histologically confirmed advanced NSCLC
• 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 Small Cell Lung Cancer (SCLC):
• Histologically confirmed SCLC
• Participants may have had prior chemotherapy, radiation therapy, or declined approved therapies for SCLC
• Additional Specific Inclusion Criteria for Participants with Esophageal Squamous Cell Carcinoma (ESCC):
• 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

You may not qualify if…

• General 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
• Additional Specific Exclusion Criteria for Participants with NSCLC who Previously Received Treatment for Metastatic Disease:
• 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)
• Additional Specific Exclusion Criteria for Participants with NSCLC who Did Not Previously Receive Treatment for Metastatic Disease:
• Prior therapy for metastatic disease
• Adjuvant anti-PD-1 or anti-PD-L1 therapy
• Additional Specific Exclusion Criteria for Participants with Small-Cell Lung Cancer (SCLC):
• Prior therapy with any immune CPIs (such as anti-PD-L1/PD-1, CTLA-4)
• Additional Specific Exclusion Criteria for Participants with Esophageal Squamous Cell Carcinoma (ESCC):
• Prior therapy with any immunomodulatory agents

Where it is running

• 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

Full record on ClinicalTrials.gov

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