Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Lomvastomig · 2 trials · 6 indications
OS was defined as the time from randomization to death from any cause. Kaplan-Meier (K-M) method was used to estimate median OS. 80% confidence interval (CI) for median was computed using the method of Brookmeyer and Crowley. IxRS=Interactive response system.
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.
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.
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.
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.
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.
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.
| Arm | Type | Description |
|---|---|---|
| Lomvastomig | EXPERIMENTAL | - |
| Tobemstomig | EXPERIMENTAL | - |
| Nivolumab | ACTIVE_COMPARATOR | - |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Name | Type | Description |
|---|---|---|
| Lomvastomig | DRUG | 2100 milligrams (mg) administered by intravenous (IV) infusion once every 2 weeks on Day 1 of each 14-day cycle. |
| Tobemstomig | DRUG | 2100 mg administered by IV infusion once every 2 weeks on Day 1 of each 14-day cycle. |
| Nivolumab | DRUG | 240 mg administered by IV infusion once every 2 weeks on Day 1 of each 14-day cycle. |
Inclusion Criteria: * Advanced or metastatic, histologically confirmed esophageal squamous-cell carcinoma (ESCC) * Patients who have previously received 1 line of treatment with either a fluoropyrimidine- and platinum- or a taxane- and platinum-based regimen in non-curative intention prior to rando...
Lomvastomig is an investigational oncology drug being studied for solid tumors, including advanced or metastatic esophageal squamous cell carcinoma. It has been evaluated in clinical trials for conditions such as metastatic melanoma, non-small cell lung cancer, small cell lung cancer, and esophageal squamous cell carcinoma.
Lomvastomig targets PD-1 and TIM-3, as it is a PD-1/TIM-3 bispecific antibody. This dual targeting is designed to modulate immune checkpoint pathways involved in cancer.
Lomvastomig is being developed by Roche Holding AG, which trades under the ticker RHHBY. Roche is conducting clinical trials to evaluate the drug's safety and efficacy in oncology indications.
Lomvastomig has completed Phase 1 and Phase 2 clinical trials. The Phase 2 study compared Lomvastomig and another investigational drug with nivolumab in participants with advanced or metastatic esophageal squamous cell carcinoma.
Lomvastomig has been studied in two completed trials. NCT03708328 was a Phase 1 dose escalation and expansion study in advanced solid tumors, and NCT04785820 was a Phase 2 study in advanced or metastatic esophageal squamous cell carcinoma.
Lomvastomig is also known as RO7121661, as indicated in the clinical trial title for the Phase 2 study. Both names refer to the same investigational drug being developed by Roche.