Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
NKTR-255 · 3 trials · 6 indications
PFS:defined as time from date of randomization to first documentation of progressive disease (PD) or death, occurring within 2 scheduled tumor assessments after last evaluable assessment or randomization. PD:at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline/ appearance of 1/more new lesions. The propensity score (PS)-based weighted Kaplan-Meier estimated median PFS times. PS were used as weights to minimize impact of confounding factors on estimation of causal treatment effects. Each participant from randomized study was assigned a weight of 1, while participants from external control received a PS-based weight with sum of weights adding up to number of participants in randomized control arm. PFS Efficacy analysis was prespecified to use a pooled control population comprising the avelumab control arm and JB100 external control cohort; therefore, results are reported for combined control population.
PFS:defined as time from date of randomization to first documentation of progressive disease (PD) or death, occurring within 2 scheduled tumor assessments after last evaluable assessment or randomization. PD:at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline/ appearance of 1/more new lesions. The propensity score (PS)-based weighted Kaplan-Meier estimated median PFS times. PS were used as weights to minimize impact of confounding factors on estimation of causal treatment effects. Each participant from randomized study was assigned a weight of 1, while participants from external control received a PS-based weight with sum of weights adding up to number of participants in randomized control arm. PFS Efficacy analysis was prespecified to use a pooled control population comprising the avelumab control arm and JB100 external control cohort; therefore, results are reported for combined control population.
PFS:defined as time from date of randomization to first documentation of progressive disease (PD) or death, occurring within 2 scheduled tumor assessments after last evaluable assessment or randomization. PD:at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline/ appearance of 1/more new lesions. The propensity score (PS)-based weighted Kaplan-Meier estimated median PFS times. PS were used as weights to minimize impact of confounding factors on estimation of causal treatment effects. Each participant from randomized study was assigned a weight of 1, while participants from external control received a PS-based weight with sum of weights adding up to number of participants in randomized control arm. PFS Efficacy analysis was prespecified to use a pooled control population comprising the avelumab control arm and JB100 external control cohort; therefore, results are reported for combined control population.
Adverse Event (AE): any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment. Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs were defined as events with onset date or worsening during the on-treatment period, defined as the time from the first dose of study intervention administration days to the last administration day + 30 days, or the start day of subsequent anticancer therapy - 1 day, whichever occurred first. TEAEs included serious AEs and non- serous AEs. AESIs included Infusion-related reactions (IRRs), Immune-related AEs (irAEs), Thromboembolic events, Cytokine release syndrome, QT interval prolongation.
Safety and tolerability of NKTR-255 in combination with cetuximab as evaluated by dose limiting toxicities, incidence of drug-related Adverse Events (AEs), SAEs, and AEs leading to discontinuation, deaths, and clinical laboratory abnormalities per CTCAE 5.0
To define the MTD and/or RP2D of NKTR-255 in combination with cetuximab in R/R HNSCC or CRC for Phase 1b Dose Escalation
Safety and tolerability of NKTR-255 as evaluated by incidence of Dose Limiting Toxicities (DLTs), drug-related Adverse Events (AEs), Serious Adverse Events (SAEs), AEs leading to discontinuation, deaths, clinical laboratory abnormalities per CTCAE v5.
Safety and tolerability of NKTR-255 in combination with daratumumab as evaluated by incidence of drug-related AEs, SAEs, AEs leading to discontinuation, deaths, clinical laboratory abnormalities per CTCAE v5
Safety and tolerability of NKTR-255 in combination with rituximab as evaluated by incidence of drug-related AEs, SAEs, AEs leading to discontinuation, deaths, clinical laboratory abnormalities per CTCAE v5
| Arm | Type | Description |
|---|---|---|
| Avelumab | EXPERIMENTAL | Participants received intravenous infusion of Avelumab at a dose of 800 mg once every 2 weeks until unacceptable toxicity, withdraw consent or initiation of a new treatment. |
| Avelumab + Sacituzumab Govitecan (SG) | EXPERIMENTAL | Participants received intravenous infusion of Avelumab at a dose of 800 milligrams (mg) once every 2 weeks in combination with intravenous infusion of SG at dose of 10 milligrams per kilogram (mg/kg) of bodyweight once a week on Day 1 and 8 of each 21-daytreatment cycles until unacceptable toxicity, withdraw consent or initiation of a new treatment. |
| Avelumab + M6223 | EXPERIMENTAL | Participants received intravenous infusion of Avelumab at a dose of 800 mg once every 2 weeks in combination with intravenous infusion of M6223 at dose of 1600 mg once every 2 weeks until unacceptable toxicity, withdraw consent or initiation of a new treatment. |
| Group D: Avelumab + NKTR-255 | EXPERIMENTAL | Participants received intravenous infusion of Avelumab at a dose of 800 mg once every 2 weeks in combination with intravenous infusion of NKTR-255 at a dose of 3 micrograms per kilogram (mcg/kg) of body weight once every 4 weeks until unacceptable toxicity, withdraw consent or initiation of a new treatment. |
| JB100 (NCT02603432) | OTHER | As per the Clinical Study Protocol, the control group (avelumab alone) was extended by data from an external control, i.e. the JAVELIN Bladder 100 study (JB100) (NCT02603432). Participants received an intravenous infusion of 10 mg/kg of Avelumab along with best supportive care (BSC), on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered asper the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anticancer therapy. |
| Dose Escalation of NKTR-255 with Cetuximab | EXPERIMENTAL | Establish RP2D, of NKTR-255 with cetuximab. |
| Dose Escalation | EXPERIMENTAL | Evaluation of NKTR-255 as: * Monotherapy * In combination with daratumumab * In combination with rituximab This phase will help to determine the RP2D of NKTR-255 |
| Dose Expansion Cohort A | EXPERIMENTAL | Evaluation of RP2D of NKTR-255 as monotherapy in patients with NHL relapsed after CAR-T |
| Dose Expansion Cohort B | EXPERIMENTAL | Evaluation of RP2D of NKTR-255 as monotherapy and in combination with SC daratumumab in patients with R/R MM |
| Dose Expansion Cohort C | EXPERIMENTAL | Evaluation of RP2D of NKTR-255 as monotherapy and in combination with rituximab in patients with R/R iNHL |
| Name | Type | Description |
|---|---|---|
| Avelumab | DRUG | Participants received intravenous infusion of Avelumab at a dose of 800 mg once every 2 weeks until unacceptable toxicity, withdraw consent or initiation of a new treatment. |
| Sacituzumab Govitecan (SG) | DRUG | Participants received intravenous infusion SG at dose of 10 mg/kg of bodyweight once a week on Day 1 and 8 of each 21-daytreatment cycles until unacceptable toxicity, withdraw consent or initiation of a new treatment. |
| M6223 | DRUG | Participants intravenous infusion of M6223 at dose of 1600 mg once every 2 weeks until unacceptable toxicity, withdraw consent or initiation of a new treatment. |
| NKTR-255 | DRUG | Participants intravenous infusion of NKTR-255 at a dose of 3 mcg/kg of body weight once every 4 weeks until unacceptable toxicity, withdraw consent or initiation of a new treatment. |
| JB100 | DRUG | As per the Clinical Study Protocol, the control group (avelumab alone) was extended by data from an external control, i.e. the JAVELIN Bladder 100 study (JB100) (NCT02603432). Participants received an intravenous infusion of 10 mg/kg of Avelumab along with best supportive care (BSC), on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered asper the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anticancer therapy. |
| Cetuximab | DRUG | Cetuximab will be given at specified doses on specified days |
| NKTR-255 Q21 | DRUG | NKTR-255 administered by IV infusion every 21 days to establish safety and tolerability |
| Rituximab | DRUG | Rituximab administered intravenously at specified dose on specified days |
| Daratumumab | DRUG | Daratumumab administered subcutaneously at specified dose on specified days |
Inclusion Criteria: * Participants with histologically confirmed, unresectable locally advanced or metastatic urothelial carcinoma. Both transitional cell and mixed transitional/non- transitional cell histologies are allowed, but transitional cell carcinoma must be the predominant histology * Parti...
NKTR-255 is an investigational oncology drug developed by Nektar Therapeutics. It is being studied in head and neck squamous cell carcinoma, locally advanced or metastatic urothelial carcinoma, and multiple myeloma. It is designed to target the IL-15 receptor and is currently in Phase 1 clinical development.
NKTR-255 targets the IL-15 receptor. By engaging this receptor, the drug is designed to stimulate immune cell activity as an immunotherapy approach in oncology. This mechanism is being evaluated in clinical trials across several cancer types, including head and neck squamous cell carcinoma, urothelial carcinoma, and multiple myeloma.
NKTR-255 is developed by Nektar Therapeutics, which trades on the Nasdaq under the ticker NKTR. The company is evaluating the drug in oncology indications including head and neck squamous cell carcinoma, locally advanced or metastatic urothelial carcinoma, and multiple myeloma.
NKTR-255 is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA. Trials have evaluated it in head and neck squamous cell carcinoma, colorectal cancer, multiple myeloma, and non-Hodgkin lymphoma, with a Phase 2 combination study ongoing in urothelial carcinoma.
NKTR-255 has been studied in NCT04616196, a completed Phase 1 trial in combination with cetuximab in solid tumors including head and neck squamous cell carcinoma, and NCT04136756, a completed Phase 1 trial in relapsed or refractory multiple myeloma and non-Hodgkin lymphoma. NCT05327530 is an active Phase 2 study in locally advanced or metastatic urothelial carcinoma.