OMVOH
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OMVOH (OMVOH).
OMVOH (nivolumab and relatlimab-rmbw) is a combination of a PD-1 immune checkpoint inhibitor (nivolumab) and a LAG-3 immune checkpoint inhibitor (relatlimab). Nivolumab binds to PD-1 receptors on T-cells, blocking interaction with PD-L1/PD-L2, thereby restoring antitumor T-cell function. Relatlimab binds to LAG-3 on T-cells, inhibiting LAG-3 interaction with MHC class II and enhancing T-cell activation. The dual blockade potentiates immune-mediated tumor cell death.
| Metabolism | Nivolumab and relatlimab are monoclonal antibodies; they are catabolized into small peptides and amino acids via general protein degradation pathways. No specific hepatic or renal metabolism is involved. |
| Excretion | Primarily eliminated via reticuloendothelial system-mediated catabolism; minimal renal excretion (<1% unchanged) and biliary/fecal excretion of intact drug is negligible. |
| Half-life | Mean terminal half-life 21 days (range 14–31 days), supporting 4-week dosing intervals. |
| Protein binding | Approximately 96% bound to plasma proteins; specific binding proteins not characterized, likely albumin and IgG-related. |
| Volume of Distribution | Approximately 3.5–5.5 L/kg (61–96 mL/kg), indicating extensive tissue distribution with retention in lymphoid tissues. |
| Bioavailability | Subcutaneous: approximately 80–90% (absolute bioavailability estimated from population PK models). |
| Onset of Action | Subcutaneous: Time to maximal pharmacodynamic effect (IL-23 suppression) approximately 8–12 weeks; clinical improvement noted as early as 4 weeks. |
| Duration of Action | Therapeutic effect sustained for at least 12 weeks after single dose, consistent with half-life; dosing every 4 weeks maintains steady-state. |
240 mg subcutaneously every 2 weeks for 12 weeks, then 240 mg subcutaneously every 4 weeks for maintenance.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²); not studied in severe impairment (eGFR <30 mL/min/1.73 m²) or dialysis. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A); not studied in moderate (Child-Pugh B) or severe (Child-Pugh C) impairment. |
| Pediatric use | Safety and efficacy not established in pediatric patients under 18 years; no recommended dose. |
| Geriatric use | No specific dose adjustment recommended; clinical studies included patients up to 75 years; monitor for adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for OMVOH (OMVOH).
| Breastfeeding | It is unknown whether OMVOH is excreted in human milk; however, human IgG antibodies are present in breast milk, and OMVOH is likely to be transferred. The M/P ratio has not been determined. Because of the potential for serious adverse reactions in the breastfed infant (e.g., immune-mediated adverse effects), breastfeeding is not recommended during treatment and for at least 5 months after the last dose. |
| Teratogenic Risk | OMVOH is a humanized monoclonal antibody (IgG4) targeting the PD-1 receptor. As an immune checkpoint inhibitor, it is expected to cross the placenta, particularly in the second and third trimesters, and may disrupt fetal immune tolerance. Based on class effect, there is a risk of immune-mediated fetal injury including increased fetal loss, spontaneous abortion, neonatal death, and premature delivery. Animal studies show increased fetal resorption and growth retardation at maternal exposures subtherapeutic to clinical doses. First trimester exposure may have less impact due to limited IgG transfer, but data are insufficient to exclude risk. OMVOH is contraindicated in pregnancy unless maternal benefit outweighs fetal risk. |
■ FDA Black Box Warning
Immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, skin adverse reactions, and myocarditis; severe and fatal immune-mediated adverse reactions may occur.
| Serious Effects |
None
| Precautions | ["Immune-mediated pneumonitis","Immune-mediated colitis","Immune-mediated hepatitis (including fatal events)","Immune-mediated endocrinopathies (adrenal insufficiency, hypophysitis, thyroid disorders, type 1 diabetes mellitus)","Immune-mediated nephritis and renal dysfunction","Immune-mediated skin adverse reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis)","Immune-mediated myocarditis","Infusion-related reactions","Embryo-fetal toxicity","Risk of rejection in transplant recipients"] |
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| Fetal Monitoring | Monitor pregnant women for signs of immune-mediated adverse reactions, including endocrinopathies (thyroid, adrenal), pneumonitis, colitis, hepatitis, nephritis, and skin reactions. Fetal monitoring with serial ultrasound to assess growth, amniotic fluid volume, and signs of hydrops or fetal immune activation. After delivery, monitor neonates for immune-mediated reactions, including endocrinopathies, hepatitis, and pneumonitis. Consider monitoring for neonatal hypophysitis and adrenal insufficiency. |
| Fertility Effects | OMVOH may impair male and female fertility based on immune-mediated effects on reproductive organs. In animal studies, testicular degeneration/atrophy and ovarian atrophy were observed. In humans, immune checkpoint inhibitors have been associated with hypogonadotropic hypogonadism, and secondary hypopituitarism can lead to infertility. Impact on human fertility has not been systematically studied. |