Avelumab With Bempegaldesleukin With or Without Talazoparib or Enzalutamide in Advanced or Metastatic Solid Tumors

DR was defined, for participants with a confirmed Objective Response (OR), as the time from the first documentation of OR to the date of first documentation of progressive disease (PD) or death due to any cause. The documentation of PD was defined using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. If a subject had not had an event (PD or death), DR was censored at the date of last adequate tumor assessment.

As there were no objective responses in the study, no participant met the definition of analysis population.

TTR was defined, for participants with objective response, as the time from the date of first dose of study treatment to the first documentation of objective response (Complete Response or Partial Response) which was subsequently confirmed.

As there were no objective responses in the study, no participant met the definition of analysis population.

Progression-Free Survival (PFS) was defined as the time from the date of first dose of study treatment to the date of the first documentation of PD or death due to any cause, whichever occurred first. PFS data were censored on the date of the last adequate tumor assessment for participants who did not have an event (PD or death), for participants who started new anti-cancer therapy prior to an event, or for participants with an event after two or more missing tumor assessments. Participants who did not have an adequate baseline tumor assessment or who did not have any adequate post-baseline tumor assessments were censored on the date of first dose of study treatment unless death occurred on or before the time of the second planned tumor assessment, in which case the death was considered an event. PFS time was summarized using the Kaplan-Meier method.

Overall survival (OS) was defined as the time from the date of first dose of study treatment to the date of death due to any cause. Participants last known to be alive were censored at date of last contact.

OS time was summarized using the Kaplan-Meier method.

Cmax was defined as the maximum observed plasma concentration at the end of infusion. Ctrough was defined as the predose concentration at the end of dosing interval.

ADA against avelumab and NKTR-214 in serum samples was determined and reported separately for ADA never-positive, ADA ever-positive participants, baseline ADA positive, treatment-boosted ADA, treatment-induced ADA, transient ADA response, persistent ADA response. For all participants, blood for ADA samples was drawn from the contralateral arm of the avelumab and NKTR-214 infusion.

nAb in serum samples was determined and reported separately for nAb never-positive, nAb ever-positive, baseline nAb positive, treatment-induced nAb, transient nAb response, persistent nAb response.

PD-L1 expression level in baseline tumor tissue, and in on-treatment tumor tissue was defined as the number of PD-L1 positive cells and/or qualitative assessment of PD-L1 staining on tumor and/or inflammatory cells in regions of interest. PD-L1 expression level in baseline tumor tissue and in on-treatment tumor tissue were under pathological analyses, assisted by image analysis. Participants were classified as positive or negative according to scoring algorithms and cut-offs established from internal or external sources.

Adverse events (AEs) were any untoward medical occurrences in a participant or clinical study participants, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Treatment-emergent adverse events (TEAEs) were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as the time from the first dose of study treatment through minimum (30 days + last dose of study treatment). A Serious Adverse Event (SAE) was defined as any untoward medical occurrence that, at any dose: a. Results in death, b. Was life-threatening, c. Required inpatient hospitalization or prolongation of existing hospitalization, d. Resulted in persistent disability/incapacity, e. Was a congenital anomaly/birth defect. Causality to study treatment was determined by the investigator.

Liver Function Tests of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBILI) were used to assess possible drug induced liver toxicity. The number of participants with at least one of the following laboratory results were summarized below: 1. (ALT ≥3 × ULN or AST ≥3 × ULN) post-baseline. 2. TBILI ≥2 × ULN post-baseline. 3. (ALP ≤2 × ULN or missing) post-baseline.