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Also known as Bempegaldesleukin, BMS-986321, BEMPEG
NKTR-214 · 4 trials · 6 indications
To evaluate the anti-tumor activity of NKTR-214 in combination with nivolumab by assessing the ORR by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) per blinded independent central review (BICR) in patients whose tumors have low programmed cell death ligand 1 (PD-L1) expression. ORR was defined as the percentage of patients with confirmed objective response of Complete Response (CR) or Partial Response (PR) on or before the first progressive disease and any subsequent anticancer therapy. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Total number, severity (CTCAE grade) of adverse events (AEs), and if AE is leading to treatment discontinuation.
Area under the serum concentration-time curve (AUC) of bempegaldesleukin calculated from time 0 to 168 hours.
Maximum observed serum concentration (Cmax) of bempegaldesleukin.
Time to maximum concentration of bempegaldesleukin. Cmax = maximum concentration. Tmax = time to maximum concentration.
Safety and Tolerability of bempegaldesleukin (starting at dose 0.00075 mg/kg) in combination with SOC was evaluated by incidence of Treatment-Emergent Adverse Events of Any Grade, Grade 3-4, and Grade 5 (Death).
Dose finding for this study was based on the assessment of DLT of bempegaldesleukin dose levels. Number and percentage of patients with any DLT were summarized by bempegaldesleukin dose level in bempegaldesleukin plus SOC treatment groups \[0.00075 mg/kg, N=5; 0.0015 mg/kg, N=5; and 0.003 mg/kg, N=5\] and placebo plus SOC (N=15). Adverse events related to study drug(s) that were defined as DLTs included the following: * Any Grade ≥ 3 drug-related AE. * Any Grade ≥ 3 drug-related laboratory abnormality that was clinically significant per the Investigator. * Respiratory compromise or other virus-related AE attributed to worsening COVID-19, such as severe hypoxia, cyanosis, or chest pain/pressure. The event was considered a DLT if it was confirmed to be at least possibly related to study drug, met any of the above definitions, and was confirmed to have occurred in a patient treated with bempegaldesleukin.
To assess the effect of bempegaldesleukin on the time course and extent of changes in absolute lymphocyte counts (ALC). Data are reported by dose and arm for Day 8 compared to baseline.
This outcome quantifies the number and types of adverse events associated with NKTR-214.
The data below reflects the incidence of Dose Limiting Toxicity Events observed in this trial.
| Arm | Type | Description |
|---|---|---|
| Combination of bempegaldesleukin (NKTR-214) + nivolumab | EXPERIMENTAL | Participants will receive bempegaldesleukin (NKTR-214) in combination with nivolumab. |
| VB10.NEO intervention | EXPERIMENTAL | Treatment with individualized VB10.NEO immunotherapy will commence as soon as the patient-specific VB10.NEO vaccine is available and if the patient-specific vaccine meets all pre-specified product release criteria after manufacturing to patients within the selected tumor types. |
| VB10.NEO in combination with bempegaldesleukin (NKTR-214) | EXPERIMENTAL | Bempegaldesleukin (NKTR-214) will be given in combination with VB10.NEO in up to 10 patients with SCCHN. Treatment with individualized VB10.NEO immunotherapy will commence as soon as the patient-specific VB10.NEO vaccine is available and if the patient-specific vaccine meets all pre-specified product release criteria after manufacturing. Bempegaldesleukin (NKTR-214) will be given after at least 4 doses of VB10.NEO. |
| Bempegaldesleukin IV + Standard of Care | EXPERIMENTAL | - |
| Placebo + Standard of Care | PLACEBO_COMPARATOR | - |
| NKTR-214 Dose Escalation | EXPERIMENTAL | This is a first in human, open-label, sequential dose escalation and expansion Phase 1 study of NKTR--214 in adult patients with locally advanced and metastatic solid tumors. The Phase 1 stage of the study is designed as an open-label dose escalation trial of NKTR--214 in participants with locally advanced or metastatic solid tumors. The goal of the dose escalation stage of the study is to find the recommended phase 2 dose, to evaluate the efficacy of NKTR--214 by assessing the objective response rate and to evaluate the safety of NKTR-214. Immunological biomarkers in plasma and tumor samples will also be measured. |
| Name | Type | Description |
|---|---|---|
| Bempegaldesleukin | BIOLOGICAL | Specified dose on specified days |
| Nivolumab | BIOLOGICAL | Specified dose on specified days |
| VB10.NEO | BIOLOGICAL | VB10.NEO is a vaccine and is supplied as a sterile, ready to use solution (14 vaccinations will be given). |
| Standard of Care | DRUG | Standard of Care Treatment for COVID-19 Infection |
| Placebo | OTHER | Administered as an intravenous infusion |
| NKTR-214 | DRUG | Participants in the dose escalation cohorts will be treated every 21 days (q21d) or every 14 days (q14d) until tumor progression. |
Key Inclusion Criteria: * Provide written, informed consent to participate in the study and follow the study procedures * Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 * Measurable disease per RECIST 1.1 criteria * Histologically or cytologically documented inoperable, locally...
NKTR-214 is an investigational small molecule being studied for the treatment of unspecified adult solid tumors, as defined by the specific protocol. It is in Phase 1 clinical development for oncology indications.
NKTR-214 is being developed by Nektar Therapeutics, a biopharmaceutical company. The company's ticker symbol is NKTR.
NKTR-214 is in Phase 1 clinical development. It is an investigational drug and has not been approved by regulatory authorities. One Phase 1 trial has been completed.
NKTR-214 has been studied in a Phase 1/2 multicenter dose escalation and expansion trial (NCT02869295) in subjects with locally advanced or metastatic solid tumors. This trial, conducted in the United States, enrolled 28 participants and has been completed.
NKTR-214 is also known as bempegaldesleukin. It is an investigational small molecule being developed by Nektar Therapeutics for the treatment of solid tumors.