Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication KEYTRUDA is a programmed death receptor-1 (PD-1)-blocking antibody indicated: Melanoma for the treatment of patients with unresectable or metastatic melanoma. ( 1.1 ) for the adjuvant treatment of adult and pediatric (12 years and older) patients with Stage IIB, IIC, or III melanoma following complete resection. FDA label
Also known as ALKS 4230, Keytruda, Nemvaleukin
Nemvaleukin alfa · 4 trials · 3 indications
ORR was defined as percentage of participants with complete response (CR) or PR as assessed by investigator based on response evaluation criteria in solid tumors (RECIST) version (v) 1.1. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis less than (\<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Changes in density (cell counts per mm2) of immune cell (including total T cells, CD8+ T cells, CD56+ cells and Treg cells) based on immunohistochemistry (IHC) and/or immunofluorescence (IF) in the TME between pretreatment and on-treatment (Cycle 2 Day 8) paired tumor biopsies
Includes AEs that are both serious and drug-related
Includes AEs that are both serious and drug-related
Overall Response rate (ORR) will be based on investigator review of radiographic and photographic images
DLT was defined by any of following events possibly, probably, or definitely related to ALKS 4230: Grade 4 neutrophil count decreased (neutropenia); Febrile neutropenia; CTCAE Grade 4 thrombocytopenia; Thrombocytopenia; Any Grade 3 cardiac or central nervous system toxicity; Liver transaminase elevation higher than 8\*upper limit of normal (ULN) or total bilirubin higher than 6\*ULN; Grade 4 hypoalbuminemia; Fever more than (\>) 40 degree Celsius (°C) sustained for \>24 hours; Hypotension required the use of pressors or prolonged hospitalization (\>48 hours) for hypotension requiring medical intervention; Grade 3 or higher electrolyte abnormalities; Increase in amylase or lipase; Grade 3 or higher nausea, vomiting, or diarrhea; Any other Grade 4 nonhematologic toxicity or any other Grade 3 non-hematologic toxicity; Any other toxicity or adverse event (AE) not defined above that resulted in participant removal from the study or discontinuation of dosing by the Investigator.
TEAEs were defined as AEs that were newly occurring or worsening from the time of the first dose of study drug. An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product.
TEAEs were defined as AEs that were newly occurring or worsening from the time of the first dose of study drug. Severity was graded according to the National Cancer Institute (NCI) CTCAE (version 4.03) where, Grade 1: Mild- asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate- minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL) Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE. As planned, Grades 1 and 2 were combined for reporting.
ORR rate was defined as the percentage of participants with objective evidence of CR or PR based on RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm). Partial Response (PR): At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
| Arm | Type | Description |
|---|---|---|
| Group 1: Nemvaleukin 3 mcg/kg + Pembrolizumab 200 mg | EXPERIMENTAL | Participants with current stable disease (SD) or partial response (PR) (Cohorts 1 and 2) who were not progressing or further demonstrating reductions in tumor size were to receive nemvaleukin alfa 3 microgram per kilogram (mcg/kg), intravenous (IV) infusion, daily from Days 1 to 5 of the first week of each 3-week treatment cycle in combination with pembrolizumab 200 milligram (mg), IV infusion, once, every three weeks (Q3W) on Day 1 of each 21-day cycle until confirmed progression, unacceptable toxicity or met other criteria for discontinuation. |
| Group 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | EXPERIMENTAL | Participants with progressive disease (PD) (Cohorts 3 and 4) received nemvaleukin alfa 3 mcg/kg, IV infusion, daily from Days 1 to 5 of the first week of each 3-week treatment cycle in combination with pembrolizumab 200 mg, IV infusion, once, Q3W on Day 1 of each 21-day cycle until confirmed progression, unacceptable toxicity or met other criteria for discontinuation. |
| Cohort 1: Tumor Microenvironment (TME) Nemvaleukin and Pembrolizumab | EXPERIMENTAL | Nemvaleukin will be administered via Intravenous (IV) infusion given daily for 5 consecutive days followed by an off-treatment period. Starting on Cycle 3, Day 1 of each cycle, Pembrolizumab will be administered via IV infusion followed by IV infusion of nemvaleukin |
| Cohort 2 Part A: Less Frequent IV Dosing Nemvaleukin | EXPERIMENTAL | - |
| Cohort 2 Part B: Less Frequent IV Dosing Nemvaleukin and Pembrolizumab | EXPERIMENTAL | This arm will not open for enrollment. |
| ALKS 4230 | EXPERIMENTAL | Administered via SC injection once every 7 days or once every 21 days at escalating doses |
| ALKS 4230 + pembrolizumab | EXPERIMENTAL | ALKS 4230 will be administered via SC injection once every 7 or 21 days at escalating doses or at the recommended phase 2 dose and schedule; pembrolizumab will be administered as an intravenous infusion given over 30 minutes; the dose level for pembrolizumab will be 200 mg per the approved label. In December 2020, an RP2D of 3 mg with an administration schedule of q7d was determined for SC ALKS 4230. |
| Name | Type | Description |
|---|---|---|
| Nemvaleukin Alfa | DRUG | Nemvaleukin alfa IV infusion. |
| Pembrolizumab | DRUG | Pembrolizumab IV infusion. |
| ALKS 4230 | BIOLOGICAL | SC injection administered in the back of the arm or the abdomen |
| ALKS 4230 + pembrolizumab | DRUG | IV infusion of ALKS 4230 over 30 minutes given daily for 5 consecutive days followed by an off-treatment period; pembrolizumab administered IV once with ALKS 4230 on the first day of each cycle |
Inclusion Criteria: * Patients must have histologically or cytopathologically confirmed diagnosis of non-cutaneous squamous cell carcinoma of the head and neck region that is locally advanced and/or recurrent and no longer amenable to local surgical or radiation therapy and/or with evidence of dist...
Nemvaleukin Alfa is an investigational oncology therapy being studied for squamous cell carcinoma of the head and neck and advanced solid tumors. It is a small molecule in Phase 2 clinical development, evaluated as a monotherapy and in combination with pembrolizumab.
Nemvaleukin Alfa is being developed by Mural Oncology plc, a biopharmaceutical company traded under the ticker MURA. The company is conducting clinical trials of the drug in oncology indications.
Nemvaleukin Alfa is in Phase 2 clinical development. It is an investigational drug, not yet approved by regulatory authorities, and is being studied in clinical trials for squamous cell carcinoma of the head and neck and advanced solid tumors.
Nemvaleukin Alfa is being studied in two clinical trials. NCT04144517 is a Phase 2 study of the drug with pembrolizumab in head and neck cancer, completed with 14 participants. NCT04592653 is a Phase 1 study of less frequent IV dosing and tumor microenvironment effects, active but not recruiting, with 78 participants in advanced solid tumors.
Yes, Nemvaleukin Alfa is also known as ALKS 4230. Clinical trial titles reference both names, such as NCT04144517, which is titled 'A Study of ALKS 4230 (Nemvaleukin Alfa) With Pembrolizumab in Head and Neck Cancer'.