A Phase 1/2, Open-Label, Multicenter Study to Investigate the Safety and Preliminary Efficacy of Combined Bempegaldesleukin (NKTR-214) and Pembrolizumab With or Without Chemotherapy in Patients With Locally Advanced or Metastatic Solid Tumors

Number of Participants Experiencing Dose-Limiting Toxicities in Dose Optimization Cohort 1a

时间窗: DLTs were assessed at 21 days from Cycle 1

DLTs were assesses in the Dose Optimization Cohort 1 a, which had doses of NKTR-214 as 0.008 mg/kg, 0.010 mg/kg, and 0.012 m/kg, I combination with pembrolizumab at 200 mg. A single DLT (hypotension) was reported in 1 patient in dose optimization Cohort 1a.

Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] for Dose Optimization Cohort 1a.

时间窗: AEs reported starting immediately after first dose of study drug(s) until 100 days after the last dose of all study drugs, up to approximately 28 months.

Safety and Tolerability of NKTR-214 (starting at dose of 0.008 mg/kg) in combination with pembrolizumab (Keytruda®) as evaluated by incidence of drug-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), AEs leading to drug discontinuation, and fatal AEs.

Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) by RECIST 1.1 of NKTR-214 Plus Pembrolizumab for Dose Expansion Cohorts 2 and 3.

时间窗: Until disease progression, death, unacceptable toxicity, symptomatic deterioration, Investigator's decision to discontinue treatment, patient withdrew consent or lost to follow-up, or study terminated by Sponsor; or until maximum of 2 years.

ORR per BICR by RECIST 1.1 for the Response Evaluable Population dose expansion Cohorts 2 and 3. ORR is defined as the proportion of enrolled participants who achieved a Best Overall Response (BOR) of CR or PR. 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. ORR is calculated as the sum of CR and PR. The Response Evaluable Population was subjects who received at least 1 dose (or partial dose) of study drug, had measurable disease (per RECIST 1.1) at baseline, and had at least 1 post-baseline assessment of tumor response.

Objective Response Rate (ORR) Per Investigator's Assessment by RECIST 1.1 of NKTR-214 at a Dose of 0.006 mg/kg With Pembrolizumab and Platinum-based Chemotherapy for Dose Expansion Cohorts 4+5.

时间窗: Until disease progression, death, unacceptable toxicity, symptomatic deterioration, Investigator's decision to discont. treatment, patient withdrew consent or lost to follow-up, or study terminated by Sponsor; or until maximum of 2 years.

ORR per Investigator's Assessment\* by RECIST 1.1 for the Response Evaluable Population dose expansion Cohorts 4 +5. The Response Evaluable Population was subjects who received at least 1 dose (or partial dose) of study drug, had measurable disease (per RECIST 1.1) at baseline, and had at least 1 post-baseline assessment of tumor response. Objective response is the sum of confirmed complete response and confirmed partial response. \*Efficacy endpoint for Cohort 4 +5 is per Investigator's Assessment due to the early termination of the study and incompleteness of BICR data for these cohorts.