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NCT03708328

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 Results posted Last updated 20 August 2025
What this trial tests

Phase 1 trial testing Lomvastomig in Solid Tumors in 134 participants. Completed in 9 July 2024.

Timeline
15 October 2018
Primary endpoint
9 July 2024
9 July 2024

Quick facts

Lead sponsorHoffmann-La Roche
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment134
Start date15 October 2018
Primary completion9 July 2024
Estimated completion9 July 2024
Sites17 locations across Denmark, France, New Zealand, South Korea, United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

18 and older, any sex, with Solid Tumors or Metastatic Melanoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Part A: Number of Participants With a Dose-Limiting Toxicity (DLT) Primary · From Cycle 1 Day 1 to Cycle 2 Day 7 (Cycle length= 14 days)

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 hemolysi

GroupValue95% CI
Part A: Lomvastomig 70 mg0
Part A: Lomvastomig 210 mg0
Part A: Lomvastomig 615 mg0
Part A: Lomvastomig 1200 mg1
Part A: Lomvastomig 1800 mg0
Part A: Lomvastomig 2100 mg0
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) Primary · From signing of informed consent form up to 60 days after last treatment administration (up to 41.7 months)

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, lo

AEs (Any grade)
GroupValue95% CI
Part A: Lomvastomig 70 mg3
Part A: Lomvastomig 210 mg5
Part A: Lomvastomig 615 mg4
Part A: Lomvastomig 1200 mg4
Part A: Lomvastomig 1800 mg3
Part A: Lomvastomig 2100 mg18
Grade 1 AE
GroupValue95% CI
Part A: Lomvastomig 70 mg0
Part A: Lomvastomig 210 mg3
Part A: Lomvastomig 615 mg1
Part A: Lomvastomig 1200 mg0
Part A: Lomvastomig 1800 mg0
Part A: Lomvastomig 2100 mg2
Grade 2 AE
GroupValue95% CI
Part A: Lomvastomig 70 mg2
Part A: Lomvastomig 210 mg1
Part A: Lomvastomig 615 mg2
Part A: Lomvastomig 1200 mg2
Part A: Lomvastomig 1800 mg1
Part A: Lomvastomig 2100 mg9
Grade 3 AE
GroupValue95% CI
Part A: Lomvastomig 70 mg1
Part A: Lomvastomig 210 mg1
Part A: Lomvastomig 615 mg1
Part A: Lomvastomig 1200 mg1
Part A: Lomvastomig 1800 mg2
Part A: Lomvastomig 2100 mg7
Grade 4 AE
GroupValue95% CI
Part A: Lomvastomig 70 mg0
Part A: Lomvastomig 210 mg0
Part A: Lomvastomig 615 mg0
Part A: Lomvastomig 1200 mg1
Part A: Lomvastomig 1800 mg0
Part A: Lomvastomig 2100 mg0
Part B: Objective Response Rate (ORR) as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Primary · 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)

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.

GroupValue95% CI
Part B1: Metastatic Melanoma Expansion Cohort7.92.19 – 19.16
Part B2: NSCLC Expansion Cohort 100.00 – 11.29
Part B4: SCLC Expansion Cohort00.00 – 18.10
Part B5: ESCC Expansion Cohort20.05.68 – 43.98
Part B: Disease Control Rate (DCR) as Determined by Investigator Using RECIST v1.1 Primary · 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)

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

GroupValue95% CI
Part B1: Metastatic Melanoma Expansion Cohort36.823.83 – 51.47
Part B2: NSCLC Expansion Cohort 136.020.24 – 54.39
Part B4: SCLC Expansion Cohort00.00 – 18.10
Part B5: ESCC Expansion Cohort60.035.96 – 80.91
Part B: Duration of Response (DOR) as Determined by Investigator Using RECIST v1.1 Primary · From first occurrence of documented OR up to disease progression or death (Up to 43.3 months) (Cycle length = 14 days)

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 bas

GroupValue95% CI
Part B1: Metastatic Melanoma Expansion Cohort17.73.9 – NA
Part B5: ESCC Expansion Cohort10.63.9 – NA
Part B: Progression Free Survival (PFS) as Determined by Investigator Using RECIST v1.1 Primary · From treatment initiation (Cycle 1 Day 1) until disease progression or death (Up to 43.3 months) (Cycle length= 14 days)

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 l

GroupValue95% CI
Part B1: Metastatic Melanoma Expansion Cohort1.81.7 – 2.0
Part B2: NSCLC Expansion Cohort 11.71.6 – 1.9
Part B4: SCLC Expansion Cohort1.71.6 – 1.8
Part B5: ESCC Expansion Cohort3.61.5 – 5.7
Parts A and B: Number of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs) Secondary · 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)

Participants were considered to be ADA positive if they were ADA negative at baseline but developed an ADA response following study drug administration (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was greater than the titer of the baseline sample by a scientifically reasonable margin such as at least 4-fold (treatment-enhanced ADA response).

GroupValue95% CI
Part A: Lomvastomig 70 mg3
Part A: Lomvastomig 210 mg2
Part A: Lomvastomig 615 mg0
Part A: Lomvastomig 1200 mg0
Part A: Lomvastomig 1800 mg1
Part A: Lomvastomig 2100 mg3
Part B1: Metastatic Melanoma Expansion Cohort5
Part B2: NSCLC Expansion Cohort 17
Part B4: SCLC Expansion Cohort1
Part B5: ESCC Expansion Cohort6
Part B: Biomarkers: T-cell Proliferation/Activation in Peripheral Blood Secondary · 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)

Biomarker analyses were performed using peripheral blood samples that were collected from participants in Part B of the study. The blood samples were assessed by flow cytometry for absolute counts of CD3⁺CD8⁺ T cells and proliferating CD3⁺CD8⁺Ki67⁺ T cells.

CD3+CD8+: Cycle 1 Day 1
GroupValue95% CI
Part B1: Metastatic Melanoma Expansion Cohort350.63± 186.81
Part B2: NSCLC Expansion Cohort 1293.25± 137.62
Part B4: SCLC Expansion Cohort252.60± 224.48
Part B5: ESCC Expansion Cohort256.00± 138.59
CD3+CD8+: Cycle 1 Day 2
GroupValue95% CI
Part B1: Metastatic Melanoma Expansion Cohort371.61± 219.58
Part B2: NSCLC Expansion Cohort 1317.28± 175.47
Part B4: SCLC Expansion Cohort296.20± 519.44
Part B5: ESCC Expansion Cohort306.50± 111.02
CD3+CD8+: Cycle 1 Day 8
GroupValue95% CI
Part B1: Metastatic Melanoma Expansion Cohort364.09± 264.35
Part B2: NSCLC Expansion Cohort 1342.59± 223.74
Part B4: SCLC Expansion Cohort292.47± 349.48
Part B5: ESCC Expansion Cohort329.00± NA
CD3+CD8+: Cycle 2 Day 1
GroupValue95% CI
Part B1: Metastatic Melanoma Expansion Cohort378.54± 250.58
Part B2: NSCLC Expansion Cohort 1298.91± 153.88
Part B4: SCLC Expansion Cohort245.93± 226.21
Part B5: ESCC Expansion Cohort257.00± 66.47
CD3+CD8+: Cycle 3 Day 1
GroupValue95% CI
Part B1: Metastatic Melanoma Expansion Cohort422.00± 380.62
Part B2: NSCLC Expansion Cohort 1310.47± 171.87
Part B4: SCLC Expansion Cohort193.18± 81.24
Part B5: ESCC Expansion Cohort199.00± NA
CD3+CD8+: Cycle 5 Day 1
GroupValue95% CI
Part B1: Metastatic Melanoma Expansion Cohort403.88± 270.34
Part B2: NSCLC Expansion Cohort 1269.00± 106.32
Part B4: SCLC Expansion Cohort234.00± 72.48
CD3+CD8+: Cycle 5 Day 2
GroupValue95% CI
Part B1: Metastatic Melanoma Expansion Cohort445.53± 228.03
Part B2: NSCLC Expansion Cohort 1285.71± 120.35
Part B4: SCLC Expansion Cohort260.50± 59.52
CD3+CD8+: Cycle 5 Day 8
GroupValue95% CI
Part B1: Metastatic Melanoma Expansion Cohort516.80± 332.31
Part B2: NSCLC Expansion Cohort 1267.57± 116.42
Part B4: SCLC Expansion Cohort179.00± 68.02
Part B: Biomarkers: CD8+ T-cell Densities in Tumor Biopsies Secondary · At screening and Cycle 3 Day 1

Fresh tumor biopsies were collected from participants in Part B of the study to assess changes in T-cell infiltration and activation within the tumor microenvironment. Tumor tissue was evaluated for CD8⁺ T-cell densities. The tumor tissue samples were collected at screening (archival metastasis and archival primary samples) and during the study (fresh samples).

Archival Metastasis Samples
GroupValue95% CI
Part B1: Metastatic Melanoma Expansion Cohort215.16± 319.52
Part B2: NSCLC Expansion Cohort 129.51± NA
Archival Primary Samples
GroupValue95% CI
Part B1: Metastatic Melanoma Expansion Cohort374.92± 530.17
Part B2: NSCLC Expansion Cohort 1764.26± 470.25
Part B5: ESCC Expansion Cohort275.02± 347.75
Fresh Sample 1
GroupValue95% CI
Part B1: Metastatic Melanoma Expansion Cohort1090.51± 1001.71
Part B2: NSCLC Expansion Cohort 1765.44± 986.47
Part B4: SCLC Expansion Cohort221.87± 363.76
Part B5: ESCC Expansion Cohort510.21± 601.10
Fresh Sample 2
GroupValue95% CI
Part B1: Metastatic Melanoma Expansion Cohort912.58± 1089.90
Part B2: NSCLC Expansion Cohort 1790.76± 462.38
Part B4: SCLC Expansion Cohort288.21± NA
Part B5: ESCC Expansion Cohort322.23± 256.74
Parts A and B: Time to Maximum Observed Serum Concentration (Tmax) of Lomvastomig Secondary · 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)
Cycle 1
GroupValue95% CI
Part A: Lomvastomig 70 mg0.090.09 – 0.17
Part A: Lomvastomig 210 mg0.090.09 – 1
Part A: Lomvastomig 615 mg0.1250.09 – 0.17
Part A: Lomvastomig 1200 mg0.170.09 – 0.26
Part A: Lomvastomig 1800 mg0.170.17 – 0.25
Part A: Lomvastomig 2100 mg0.090.09 – 0.19
Part A: Lomvastomig 2100 mg (Extension Cohort 1)0.1750.17 – 0.25
Part A: Lomvastomig 2100 mg (Extension Cohort 2)0.180.09 – 0.28
Part B1: Metastatic Melanoma Expansion Cohort0.170.04 – 1.24
Part B2: NSCLC Expansion Cohort 10.10.04 – 0.18
Part B4: SCLC Expansion Cohort0.170.09 – 0.91
Part B5: ESCC Expansion Cohort0.170.08 – 0.25
Cycle 5
GroupValue95% CI
Part A: Lomvastomig 70 mg0.160.16 – 0.16
Part A: Lomvastomig 210 mg0.170.09 – 0.25
Part A: Lomvastomig 615 mg2.51 – 4.01
Part A: Lomvastomig 1200 mg3.571.12 – 6.02
Part A: Lomvastomig 1800 mg0.170.17 – 0.17
Part A: Lomvastomig 2100 mg0.170.17 – 0.17
Part A: Lomvastomig 2100 mg (Extension Cohort 1)0.210.09 – 0.22
Part A: Lomvastomig 2100 mg (Extension Cohort 2)0.2150.09 – 0.23
Part B1: Metastatic Melanoma Expansion Cohort0.10 – 0.98
Part B2: NSCLC Expansion Cohort 10.10.02 – 3.13
Part B4: SCLC Expansion Cohort0.110.03 – 0.11
Part B5: ESCC Expansion Cohort0.10.01 – 0.88
Parts A and B: Maximum Observed Serum Concentration (Cmax) of Lomvastomig Secondary · 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)
Cycle 1
GroupValue95% CI
Part A: Lomvastomig 70 mg21.5± 40.0
Part A: Lomvastomig 210 mg61.7± 25.2
Part A: Lomvastomig 615 mg148± 18.5
Part A: Lomvastomig 1200 mg408± 5.7
Part A: Lomvastomig 1800 mg530± 20.8
Part A: Lomvastomig 2100 mg518± 8.8
Part A: Lomvastomig 2100 mg (Extension Cohort 1)575± 29.4
Part A: Lomvastomig 2100 mg (Extension Cohort 2)740± 14.4
Part B1: Metastatic Melanoma Expansion Cohort791± 43.3
Part B2: NSCLC Expansion Cohort 1704± 26.2
Part B4: SCLC Expansion Cohort726± 16.1
Part B5: ESCC Expansion Cohort754± 24.5
Cycle 5
GroupValue95% CI
Part A: Lomvastomig 70 mg20.2± NA
Part A: Lomvastomig 210 mg128± 8.3
Part A: Lomvastomig 615 mg116± 116.9
Part A: Lomvastomig 1200 mg546± 14.8
Part A: Lomvastomig 1800 mg781± 30.8
Part A: Lomvastomig 2100 mg1600± NA
Part A: Lomvastomig 2100 mg (Extension Cohort 1)1500± 0.0
Part A: Lomvastomig 2100 mg (Extension Cohort 2)1520± 17.5
Part B1: Metastatic Melanoma Expansion Cohort1420± 32.6
Part B2: NSCLC Expansion Cohort 11270± 33.1
Part B4: SCLC Expansion Cohort1240± 23.0
Part B5: ESCC Expansion Cohort1280± 25.7
Parts A and B: Maximum Observed Serum Concentration Dose Normalized (Cmax_D) of Lomvastomig Secondary · 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)
Cycle 1
GroupValue95% CI
Part A: Lomvastomig 70 mg0.307± 40.0
Part A: Lomvastomig 210 mg0.294± 25.3
Part A: Lomvastomig 615 mg0.24± 18.5
Part A: Lomvastomig 1200 mg0.34± 5.7
Part A: Lomvastomig 1800 mg0.295± 20.9
Part A: Lomvastomig 2100 mg0.246± 8.8
Part A: Lomvastomig 2100 mg (Extension Cohort 1)0.274± 29.4
Part A: Lomvastomig 2100 mg (Extension Cohort 2)0.352± 14.3
Part B1: Metastatic Melanoma Expansion Cohort0.377± 43.2
Part B2: NSCLC Expansion Cohort 10.335± 26.2
Part B4: SCLC Expansion Cohort0.346± 16.1
Part B5: ESCC Expansion Cohort0.359± 24.4
Cycle 5
GroupValue95% CI
Part A: Lomvastomig 70 mg0.777± NA
Part A: Lomvastomig 210 mg0.608± 8.4
Part A: Lomvastomig 615 mg0.188± 117.0
Part A: Lomvastomig 1200 mg0.455± 14.8
Part A: Lomvastomig 1800 mg0.434± 30.8
Part A: Lomvastomig 2100 mg0.762± NA
Part A: Lomvastomig 2100 mg (Extension Cohort 1)0.714± 0.0
Part A: Lomvastomig 2100 mg (Extension Cohort 2)0.725± 17.5
Part B1: Metastatic Melanoma Expansion Cohort0.675± 32.6
Part B2: NSCLC Expansion Cohort 10.607± 33.0
Part B4: SCLC Expansion Cohort0.592± 22.9
Part B5: ESCC Expansion Cohort0.609± 25.8

Adverse events — posted to ClinicalTrials.gov

Time frame: Part A: From signing of informed consent form up to 60 days after last treatment administration (up to 41.7 months); Part B: From signing of informed consent form up to 90 days after last treatment administration (up to 46.2 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part A: Lomvastomig 70mg
Serious: 1/3 (33%)
Deaths: 3/3
Part A: Lomvastomig 210 mg
Serious: 1/5 (20%)
Deaths: 3/5
Part A: Lomvastomig 615 mg
Serious: 1/4 (25%)
Deaths: 4/4
Part A: Lomvastomig 1200 mg
Serious: 1/4 (25%)
Deaths: 2/4
Part A: Lomvastomig 1800 mg
Serious: 1/4 (25%)
Deaths: 2/4
Part A: Lomvastomig 2100 mg
Serious: 7/19 (37%)
Deaths: 13/19
Part B1: Metastatic Melanoma Expansion Cohort
Serious: 6/38 (16%)
Deaths: 26/38
Part B2: NSCLC Expansion Cohort 1
Serious: 8/26 (31%)
Deaths: 18/26
Part B4: SCLC Expansion Cohort
Serious: 4/15 (27%)
Deaths: 13/15
Part B5: ESCC Expansion Cohort
Serious: 10/16 (63%)
Deaths: 8/16

Serious adverse events (50 terms)

ReactionSystemPart A: Lomvastomig 70mgPart A: Lomvastomig 210 mgPart A: Lomvastomig 615 mgPart A: Lomvastomig 1200 mgPart A: Lomvastomig 1800 mgPart A: Lomvastomig 2100 mgPart B1: Metastatic Melano…Part B2: NSCLC Expansion C…Part B4: SCLC Expansion Co…Part B5: ESCC Expansion Co…
PneumoniaInfections and infestations
AnaemiaBlood and lymphatic system disorders
Atrial fibrillationCardiac disorders
RetinopathyEye disorders
Abdominal painGastrointestinal disorders
ColitisGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
DysphagiaGastrointestinal disorders
Gastric haemorrhageGastrointestinal disorders
HaematemesisGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
Obstruction gastricGastrointestinal disorders
Oesophageal stenosisGastrointestinal disorders
Small intestinal perforationGastrointestinal disorders
Bile duct stenosisHepatobiliary disorders
CholangitisHepatobiliary disorders
CholecystitisHepatobiliary disorders
Appendicitis perforatedInfections and infestations
BronchitisInfections and infestations
CellulitisInfections and infestations
Gallbladder abscessInfections and infestations
Phlebitis infectiveInfections and infestations
SepsisInfections and infestations
Urinary tract infectionInfections and infestations
False positive investigation resultInvestigations
Other adverse events (181 terms — click to expand)

ReactionSystemPart A: Lomvastomig 70mgPart A: Lomvastomig 210 mgPart A: Lomvastomig 615 mgPart A: Lomvastomig 1200 mgPart A: Lomvastomig 1800 mgPart A: Lomvastomig 2100 mgPart B1: Metastatic Melano…Part B2: NSCLC Expansion C…Part B4: SCLC Expansion Co…Part B5: ESCC Expansion Co…
AstheniaGeneral disorders
VomitingGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
NauseaGastrointestinal disorders
ConstipationGastrointestinal disorders
FatigueGeneral disorders
ArthralgiaMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
Oedema peripheralGeneral disorders
PyrexiaGeneral disorders
Abdominal painGastrointestinal disorders
Weight decreasedInvestigations
HeadacheNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
Urinary tract infectionInfections and infestations
Aspartate aminotransferase increasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
HypophosphataemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
LymphopeniaBlood and lymphatic system disorders
Abdominal pain upperGastrointestinal disorders
DysphagiaGastrointestinal disorders
PneumoniaInfections and infestations
Alanine aminotransferase increasedInvestigations
Blood alkaline phosphatase increasedInvestigations
Gamma-glutamyltransferase increasedInvestigations
HypercalcaemiaMetabolism and nutrition disorders
HypoalbuminaemiaMetabolism and nutrition disorders
Tumour painNeoplasms benign, malignant and unspecified (incl cysts and polyps)
DizzinessNervous system disorders
SomnolenceNervous system disorders
AnxietyPsychiatric disorders
HaemoptysisRespiratory, thoracic and mediastinal disorders
Productive coughRespiratory, thoracic and mediastinal disorders
RashSkin and subcutaneous tissue disorders
Adrenal insufficiencyEndocrine disorders

Most-reported serious reactions: Pneumonia, Anaemia, Atrial fibrillation, Retinopathy, Abdominal pain, Colitis, Diarrhoea, Dysphagia.

Data from ClinicalTrials.gov NCT03708328 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4.
    Qin S, Xu L, Yi M, Yu S, et al · · 2019 · cited 909× · PMID 31690319 · DOI 10.1186/s12943-019-1091-2
  2. TIM3 comes of age as an inhibitory receptor.
    Wolf Y, Anderson AC, Kuchroo VK. · · 2020 · cited 755× · PMID 31676858 · DOI 10.1038/s41577-019-0224-6
  3. Tumor biomarkers for diagnosis, prognosis and targeted therapy.
    Zhou Y, Tao L, Qiu J, Xu J, et al · · 2024 · cited 379× · PMID 38763973 · DOI 10.1038/s41392-024-01823-2
  4. Influence of the Tumor Microenvironment on NK Cell Function in Solid Tumors.
    Melaiu O, Lucarini V, Cifaldi L, Fruci D. · · 2019 · cited 324× · PMID 32038612 · DOI 10.3389/fimmu.2019.03038
  5. Tim-3 finds its place in the cancer immunotherapy landscape.
    Acharya N, Sabatos-Peyton C, Anderson AC. · · 2020 · cited 313× · PMID 32601081 · DOI 10.1136/jitc-2020-000911
  6. Emerging new therapeutic antibody derivatives for cancer treatment.
    Jin S, Sun Y, Liang X, Gu X, et al · · 2022 · cited 304× · PMID 35132063 · DOI 10.1038/s41392-021-00868-x
  7. Immunotherapy in Lung Cancer: Current Landscape and Future Directions.
    Mamdani H, Matosevic S, Khalid AB, Durm G, et al · · 2022 · cited 253× · PMID 35222404 · DOI 10.3389/fimmu.2022.823618
  8. Immunotherapeutic approaches for small-cell lung cancer.
    Iams WT, Porter J, Horn L. · · 2020 · cited 237× · PMID 32055013 · DOI 10.1038/s41571-019-0316-z

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