Phase 1
Completed N=134
A Dose Escalation and Expansion Study of Lomvastomig, a PD-1/TIM-3 Bispecific Antibody, in Participants With Advanced and/or Metastatic Solid Tumors
Solid Tumors · Metastatic Melanoma · Non-small Cell Lung Cancer (NSCLC) · Small Cell Lung Cancer (SCLC)
Source: ClinicalTrials.gov NCT03708328 ↗
Enrolled (actual)
134
Serious AEs
29.8%
Results posted
Aug 2025
Primary outcomePrimary: Part A: Number of Participants With a Dose-Limiting Toxicity (DLT) — 0; 0; 0; 1 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part A: Number of Participants With a Dose-Limiting Toxicity (DLT) |
0; 0; 0; 1; 0; 0 | — |
| PRIMARY 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) |
3; 5; 4; 4; 3; 18 | — |
| PRIMARY Part B: Objective Response Rate (ORR) as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) |
7.9; 0; 0; 20.0 | — |
| PRIMARY Part B: Disease Control Rate (DCR) as Determined by Investigator Using RECIST v1.1 |
36.8; 36.0; 0; 60.0 | — |
| PRIMARY Part B: Duration of Response (DOR) as Determined by Investigator Using RECIST v1.1 |
17.7; 10.6 | — |
| PRIMARY Part B: Progression Free Survival (PFS) as Determined by Investigator Using RECIST v1.1 |
1.8; 1.7; 1.7; 3.6 | — |
| SECONDARY Parts A and B: Number of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs) |
3; 2; 0; 0; 1; 3 | — |
| SECONDARY Part B: Biomarkers: T-cell Proliferation/Activation in Peripheral Blood |
350.63; 293.25; 252.60; 256.00; 371.61; 317.28 | — |
| SECONDARY Part B: Biomarkers: CD8+ T-cell Densities in Tumor Biopsies |
215.16; 29.51; 374.92; 764.26; 275.02; 1090.51 | — |
| SECONDARY Parts A and B: Time to Maximum Observed Serum Concentration (Tmax) of Lomvastomig |
0.09; 0.09; 0.125; 0.17; 0.17; 0.09 | — |
| SECONDARY Parts A and B: Maximum Observed Serum Concentration (Cmax) of Lomvastomig |
21.5; 61.7; 148; 408; 530; 518 | — |
| SECONDARY Parts A and B: Maximum Observed Serum Concentration Dose Normalized (Cmax_D) of Lomvastomig |
0.307; 0.294; 0.24; 0.34; 0.295; 0.246 | — |
| SECONDARY Parts A and B: Time to Last Non-zero Concentration (Tlast) of Lomvastomig |
14; 14; 14; 14; 14; 14 | — |
| SECONDARY Parts A and B: Last Non-zero Concentration (Clast) of Lomvastomig |
5.52; 21.4; 40.4; 116; 147; 157 | — |
| SECONDARY Parts A and B: Area Under the Curve From Dosing to Last Concentration (AUClast) of Lomvastomig |
140; 426; 927; 2540; 3040; 2700 | — |
| SECONDARY Parts A and B: Area Under the Curve From Dosing to 336 Hours Post-dose (AUC0-336 Hrs) of Lomvastomig |
140; 427; 932; 2600; 3120; 3180 | — |
| SECONDARY Part A: Receptor Occupancy (RO) of Lomvastomig, Assessed Via an Ex-Vivo Assay |
41.80; 36.23; 34.77; 0.28; 14.37; 70.43 | — |
| SECONDARY Part B: Number of Participants With at Least One AE by Highest Severity, Graded According to the NCI CTCAE v5.0 |
34; 25; 15; 16; 7; 5 | — |
| SECONDARY Part A: ORR as Determined by Investigator Using RECIST v1.1 |
0; 0; 0; 0; 0; 21.1 | — |
| SECONDARY Part A: DCR as Determined by Investigator Using RECIST v1.1 |
33.3; 40.0; 0; 50.0; 25.0; 42.1 | — |
| SECONDARY Part A: DOR as Determined by Investigator Using RECIST v1.1 |
13.8 | — |
| SECONDARY Part A: PFS as Determined by Investigator Using RECIST v1.1 |
1.8; 2.0; 1.6; NA; 1.8; 1.9 | — |
Eligibility Criteria
Inclusion Criteria
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
Exclusion Criteria
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)
Data sourced from ClinicalTrials.gov (NCT03708328). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.