NT-I7 (Efineptakin Alfa) in Combination With Pembrolizumab in Participants With Advanced Solid Tumors

A TEAE was any AE that starts on/after the first day of trial treatment or that worsens on/after the first day of trial treatment and up to 30 days (90 days for serious adverse events) after the date of last dose of trial drugs, or initiation of new anticancer therapy, whichever is earlier. A SAE was defined as any AE that resulted in any of the following outcomes:

• Death;
• A life-threatening AE;
• An AE that resulted in inpatient hospitalization or prolongation of existing hospitalization for ≥24 hours;
• A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions;
• A congenital anomaly/birth defect;
• Important Medical Events (IME) that may not result in death, be life threatening, or require hospitalization may be considered serious when, based upon medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.

A DLT was defined as any AE occurring within the first 21 days that was considered to be related to the trial treatments (NT-I7 and/or pembrolizumab) per the investigator, and that met at least one of the non-hematologic or hematologic criteria:

• Grade 4 non-hematologic toxicity
• Grade ≥ 3 diarrhea, nausea and vomiting
• Grade ≥ 3 rash for ≥ 5 days
• Grade 4 neutropenia for ≥ 5 days
• Febrile neutropenia Grade 3 or Grade 4
• Other Grade 4 hematologic toxicity for ≥7 days, except thrombocytopenia
• Any non-hematologic AE ≥ Grade 3 in severity
• Any Grade 3 or Grade 4 non-hematologic laboratory value if medical intervention was required, led to hospitalization, persisted for > 1 week, resulted in potential drug-induced liver injury
• Other Grade ≥ 3 clinical laboratory abnormalities not reversible to ≤ Grade 1 within 72 hours
• Prolonged delay in initiating Cycle 2
• Any treatment-related toxicity that caused treatment discontinuation in Cycle 1
• Grade 5 toxicity.

ORR was defined as the percentage of participants who had at least one confirmed partial response (PR) or complete response (CR), per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST v1.1) and immune RECIST (iRECIST) as determined by the investigator. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to <10 mm (<1 cm). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

CD8 positivity TILs in tumor biopsy samples were identified using a validated immunohistochemistry (IHC) assay and certified by a pathologist. The percentage of area occupied by TILs was evaluated in the stroma area, tumor area and tumor - relevant tissue area both pre- and post-treatment.

ORR was defined as the percentage of participants who had at least one confirmed PR or CR, per RECIST v1.1 and iRECIST as determined by the investigator. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to <10 mm (<1 cm). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

DOR was defined as the time from the first occurrence of a documented objective response to the time of the first documented disease progression or death from any cause, whichever occurs first, per RECIST 1.1 and iRECIST as determined by the investigator.

DCR was defined as the proportion of participants with a best overall response of CR, PR, stable disease (SD) per RECIST 1.1 and iRECIST as determined by the investigator..

SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) at least a 20% increase in the sum of the diameters of target lesions), taking as reference the smallest sum diameters while on study.

PFS was defined as the time from the first trial treatment (Cycle 1, Day 1) to the first occurrence of progression or death from any cause, whichever occurs first per RECIST 1.1 and iRECIST as determined by the investigator.

PD was defined as at least a 20% increase in the sum of the diameters of target lesions, using the smallest sum observed on study as reference, with an absolute increase of at least 5 mm, or the appearance of new lesions, or unequivocal progression of non-target lesions, per RECIST 1.1.

OS was defined as the time from first trial treatment (Cycle 1, Day 1) to death from any cause.

Immunogenicity to NT-I7 was measured using a risk-based, tiered testing approach. This included screening and confirmatory assays for binding ADAs, epitope-specific assays to characterize ADA reactivity to whole NT-I7 vs IL-7 domain, and a cell-based neutralizing ADA assay for IL7 bioactivity. Participants' samples were obtained at baseline and over the course of treatment (to evaluate the prevalence and incidence of treatment-emergent/boosted ADA).

Not detected or detected but not confirmed ADA was defined as negative. Detected and confirmed ADA was defined as positive.

A TEAE was any AE that starts on/after the first day of trial treatment or that worsens on/after the first day of trial treatment and up to 30 days (90 days for serious adverse events) after the date of last dose of trial drugs, or initiation of new anticancer therapy, whichever is earlier. A SAE was defined as any AE that resulted in any of the following outcomes:

Death; A life-threatening AE; An AE that resulted in inpatient hospitalization or prolongation of existing hospitalization for ≥24 hours; A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; A congenital anomaly/birth defect; Important Medical Events (IME) that may not result in death, be life threatening, or require hospitalization may be considered serious when, based upon medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.