Mirvetuximab Soravtansine Sample Clauses

Mirvetuximab Soravtansine. Because of its tumor specific expression and capacity to internalize small and large molecule ligands, FRα has emerged as a promising target for antibody drug conjugate (ADC) therapy. ADCs combine the specificity of mAb to tumor antigens with the extraordinary cytotoxicity of maytansine derivatives, which are potent anti-microtubule agents that target proliferating cells. MIRV is an ADC designed to target FRα. It consists of the humanized anti- FRα mAb M9346A attached via a cleavable disulfide linker to the cytotoxic maytansinoid, DM4 (Figure 1).

Mirvetuximab Soravtansine. The selection of the Phase 3 dose of 6 mg/kg AIBW IV Q3W was based on data obtained from Study IMGN853-0401, a FIH study designed to establish the MTD and determine the recommended phase 2 dose (RP2D) of MIRV when administered IV as a single agent in adult patients with FRα-positive solid tumors who have relapsed or are refractory to standard therapies. The appropriateness of this dose and regimen in patients with PROC was further supported by the results of the Phase 3 study IMGN853-0403. For more information please see the Investigator Brochure.

Mirvetuximab Soravtansine. The investigational study drug, MIRV, will be provided by ImmunoGen, at a protein concentration of 5.0 mg/mL in an aqueous pH 5.0 buffered solution. See the Investigator Xxxxxxxx for complete list of excipients.

Mirvetuximab Soravtansine. All patients receiving MIRV must receive 325-650 mg of acetaminophen/paracetamol (PO or IV), 10 mg IV dexamethasone, and 25-50 mg diphenhydramine (IV or PO) (equivalent drugs of similar drug classes is also acceptable) approximately 30 min before each infusion of MIRV. If individual patients require more intensive treatment to prevent infusion-related reactions (IRRs), investigators may modify the regimen accordingly. An antiemetic medication (eg, 5-HT3 serotonin receptor antagonists such as palonosetron, granisetron or ondansetron or appropriate alternatives) is recommended before each MIRV dose and may be used any time at the discretion of the treating physician.

Mirvetuximab Soravtansine related Adverse Events Dose modifications for MIRV-related adverse events are described in Table 6. Table 6: Dose Modifications for Mirvetuximab Soravtansine-related Adverse Events Severity Grade (CTCAE) Dose Modifications for MIRV a Hematological Neutropenia Grade 2 and Grade 3 Hold drug until ANC is ≥ 1.5 x109/L (1500 /μL) and resume at the same dose level Grade 4 Hold drug until ANC is ≥ 1.5 x109/L (1500 /μL) and then resume at one lower dose level Febrile neutropenia Grade 3 or 4 (with a single temperature reading ≥ 38.3°C or a sustained temperature of > 38°C for > one h) Hold drug until ANC is ≥ 1.5 x109/L (1500 /μL) and then resume at one lower dose level Thrombocytopenia Grade 2 and Grade 3 Hold drug until PLT count is ≥ 100 x 109/L (100,000/μL) and resume at same dose level Grade 3 associated with clinically significant bleeding that requires transfusion therapy and Grade 4 Hold drug until PLT count is ≥ 100 x 109/L (100,000/μL) and then resume at one lower level Non-hematological Nausea and Vomiting Grade 3 (despite use of optimal antiemetics) Hold drug until resolved to ≤ Grade 1, then resume at one lower level Grade 4 Permanently discontinue Diarrhea Grade 3 (despite use of optimal anti-diarrheal treatment) Hold drug until resolved to ≤ Grade 1, then resume at one lower level Grade 4 Permanently discontinue Ocular Disorders Refer to Section 5.6.1.6 Noninfectious Pneumonitis Refer to Section 5.6.1.7 Infusion-related Reactions Refer to Section 5.6.1.9 All Other Non-hematological Toxicities (except AEs related to underlying disease, Grade 3 fatigue, isolated symptomatic Grade 3 biochemistry laboratory abnormalities that last for < 7 days including electrolyte abnormalities that respond to medical intervention) Grade 3 Hold drug until resolved to ≤ Grade 1, then resume at one lower level For any Grade 3 hepatic toxicity that does not resolve to baseline within seven days, an abdominal CT scan must be performed to assess whether it is related to disease progression. ≥ Grade 3 Cardiac events (excluding Grade 3 hypertension) Permanently discontinue Grade 4 non-hematological toxicities Permanently discontinue Abbreviations: CTCAE = common terminology criteria for adverse events; ANC = absolute neutrophil count; PLT = platelets; CT = computed tomography; AE = adverse event. a Failure to meet retreatment criteria within 1 cycle (21 days) after the missed dose due to insufficient recovery from a treatment-related toxicity will results in treatment disconti...