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

NCT03708328 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: NP404352018-000982-35
• Study Type: interventional
• Target: 134
• Locations: 6 countries
• Sites: 17

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)

Outcome Measures

Primary Outcomes (6)

• Part A: Number of Participants With a Dose-Limiting Toxicity (DLT)

  A DLT was defined as a clinically significant adverse event (AE) or significant laboratory abnormality: 1) occurring during DLT assessment period of 21 days; 2) considered to be related to study treatment RO7121661 by the Investigator; 3) is not attributed to disease progression or another clearly identifiable cause. Following AEs were considered DLTs: Hematological toxicities (Grade 4 neutropenia lasting \>5 days, Grade ≥3 febrile neutropenia, Grade 4 thrombocytopenia lasting \> 48 hours, Grade 3 thrombocytopenia associated with bleeding episodes, Grade 4 anemia, Grade ≥3 anemia with hemolysis); Non-hematological toxicity Grade ≥3 (Any Grade 3 immune-mediated AE, Grade 3 hyperbilirubinemia lasting for \>48 hours/Grade 4 hyperbilirubinemia; Grade ≥3 aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevations with hyperbilirubinemia of Grade ≥2, Grade 4 AST or ALT elevations, Grade ≥3 nausea, vomiting, or diarrhea, Grade ≥3 non-hematological laboratory abnormality.

  From Cycle 1 Day 1 to Cycle 2 Day 7 (Cycle length= 14 days)

• Part A: Number of Participants With at Least One AE by Highest Severity, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)

  AE=any untoward medical occurrence in a participant administered a pharmaceutical product \& which does not necessarily have a causal relationship with treatment \& can therefore be any unfavorable \& unintended sign (including abnormal laboratory values/abnormal clinical test results), symptoms/disease temporally associated with the use of pharmaceutical product, whether or not considered related to pharmaceutical product. Severity of AEs was graded as: Grade 1=Mild, asymptomatic/mild symptoms, clinical/diagnostic observations only, or intervention not indicated; Grade 2=Moderate, minimal, local/non-invasive intervention indicated, or limiting age-appropriate instrumental activities of daily living; Grade 3=Severe/medically significant but not immediately life-threatening, hospitalization/prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living; Grade 4= Life-threatening consequences, urgent intervention indicated; Grade 5=Death related to AE.

  From signing of informed consent form up to 60 days after last treatment administration (up to 41.7 months)

• Part B: Objective Response Rate (ORR) as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

  ORR was defined as the percentage of participants with an objective tumor response of complete response (CR) or partial response (PR) as determined by the investigator using RECIST v.1.1. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) have a reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the baseline SOD.

  Cycle 1 Day 1 then every 8 weeks for the first year; every 12 weeks thereafter until disease progression or treatment discontinuation (whichever occurs last), initiation of a new line of therapy or death (Up to 43.3 months) (Cycle length= 14 days)

• Part B: Disease Control Rate (DCR) as Determined by Investigator Using RECIST v1.1

  DCR was defined as the percentage of participants with an objective tumor response of CR, PR or stable disease (SD) as determined by the investigator using RECIST v.1.1. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) have a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression (PD). PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on the study including baseline (nadir). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

  Cycle 1 Day 1 then every 8 weeks for the first year; every 12 weeks thereafter until disease progression or treatment discontinuation (whichever occurs last), initiation of a new line of therapy or death (Up to 43.3 months) (Cycle length= 14 days)

• Part B: Duration of Response (DOR) as Determined by Investigator Using RECIST v1.1

  DOR was calculated for participants who had a best confirmed overall response (OR) of CR/PR. DOR was defined as time from first occurrence of a documented OR until the time of documented PD or death (within 30 days from last treatment) from any cause, whichever occurs first as determined by investigator assessment using RECIST v1.1. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on the study including baseline (nadir). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Data for participants without PD or death as of the data cut-off date were censored at the time of the last tumor assessment.

  From first occurrence of documented OR up to disease progression or death (Up to 43.3 months) (Cycle length = 14 days)

• Part B: Progression Free Survival (PFS) as Determined by Investigator Using RECIST v1.1

  PFS was defined as the time from study treatment initiation (Cycle 1 Day 1) to the first occurrence of documented PD, as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Data for participants without PD or death as of the data cut-off date were censored at the time of the last tumor assessment.

  From treatment initiation (Cycle 1 Day 1) until disease progression or death (Up to 43.3 months) (Cycle length= 14 days)

Secondary Outcomes (16)

• Parts A and B: Number of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs)

  Baseline and Day 1 of Cycles 1 to 5; Day 1 of Cycle 7, and every 6 cycles thereafter (1 cycle is 14 days); study completion/discontinuation; safety follow-up visits (up to approximately 40.8 months - Part A and 45.4 months - Part B)

• Part B: Biomarkers: T-cell Proliferation/Activation in Peripheral Blood

  Days 1, 2, and 8 of Cycles 1 and 5; Day 1 of Cycles 2, 3, and 9 (1 cycle is 14 days); study completion visit (28 days after last dose; up to 43.3 months); safety follow-up (SFU) (90 days after last dose; up to 45.4 months)

• Part B: Biomarkers: CD8+ T-cell Densities in Tumor Biopsies

  At screening and Cycle 3 Day 1

• Parts A and B: Time to Maximum Observed Serum Concentration (Tmax) of Lomvastomig

  Predose, half infusion, end of infusion (EOI), 0.5, 2, 4, and 8 hours postdose on Cycle 1 Day 1 and Cycle 5 Day 1, and on Cycles 1 and 5 Days 2, 3, 4, 5, 8, and 12, and predose on Day 1 of Cycles 2 and 6 (1 cycle = 14 days)

• Parts A and B: Maximum Observed Serum Concentration (Cmax) of Lomvastomig

  Predose, half infusion, end of infusion (EOI), 0.5, 2, 4, and 8 hours postdose on Cycle 1 Day 1 and Cycle 5 Day 1, and on Cycles 1 and 5 Days 2, 3, 4, 5, 8, and 12, and predose on Day 1 of Cycles 2 and 6 (1 cycle = 14 days)

Study Arms (6)

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

EXPERIMENTAL

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.

Drug: Lomvastomig

Expansion Part B1: Metastatic Melanoma Cohort

EXPERIMENTAL

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.

Drug: Lomvastomig

Expansion Part B2: NSCLC Cohort 1

EXPERIMENTAL

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.

Drug: Lomvastomig

Expansion Part B3: NSCLC Cohort 2

EXPERIMENTAL

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.

Drug: Lomvastomig

Expansion Part B4: SCLC Cohort

EXPERIMENTAL

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.

Drug: Lomvastomig

Expansion Part B5: ESCC Cohort

EXPERIMENTAL

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.

Drug: Lomvastomig

Interventions

Lomvastomig DRUG

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

Also known as: RO7121661, RG7769

Dose Escalation Part A: Once Every 2 Weeks (Q2W); Expansion Part B1: Metastatic Melanoma Cohort; Expansion Part B2: NSCLC Cohort 1; Expansion Part B3: NSCLC Cohort 2; Expansion Part B4: SCLC Cohort; Expansion Part B5: ESCC Cohort

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (17)

Columbia Univ Med Ctr

New York, New York, 10032, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Herlev Hospital

Herlev, 2730, Denmark

Location

Rigshospitalet

København Ø, 2100, Denmark

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

CHU Timone

Marseille, 13005, France

Location

ICO Rene Gauducheau

Saint-Herblain, 44805, France

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

Seoul National University Hospital

Seoul, 03080, 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

Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

START Madrid-FJD, Hospital Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

MeSH Terms

Conditions

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

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: October 9, 2018
• First Posted: October 17, 2018
• Study Start: October 15, 2018
• Primary Completion: July 9, 2024
• Study Completion: July 9, 2024
• Last Updated: August 20, 2025
• Results First Posted: August 20, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

KR (3); ES (5); US (2); FR (4); DK (2); NZ (1)