Objective response rate according to RECIST 1.1 was defined as the proportion of participants with complete response according to RECIST 1.1 or partial response according to RECIST 1.1 for target lesions and assessed by CT/MRI. Participants with missing data were considered non-responders.

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

Objective response rate according to iRECIST was defined as the proportion of participants with complete response according to iRECIST or partial response according to iRECIST for target lesions and assessed by CT/MRI. Participants with missing data were considered non-responders.

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

The best overall response according to RECIST 1.1 was defined as the best response from the start of study treatment until the first documented disease progression, death, or start of new anti-cancer therapy for target lesions and assessed by CT/MRI.

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

The best overall response according to RECIST 1.1 was defined as the best response from the start of study treatment until the first documented disease progression, death, or start of new anti-cancer therapy for target lesions and assessed by CT/MRI.

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

The best overall response according to RECIST 1.1 was defined as the best response from the start of study treatment until the first documented disease progression, death, or start of new anti-cancer therapy for target lesions and assessed by CT/MRI. Stable disease according to RECIST 1.1 had to last at least 6 weeks from the start of study treatment. If not, at least 1 follow-up scan was required to declare stable disease.

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

The best overall response according to RECIST 1.1 was defined as the best response from the start of study treatment until the first documented disease progression, death, or start of new anti-cancer therapy for target lesions and assessed by CT/MRI.

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

The best overall response according to iRECIST was defined as the best response from the start of study treatment until the first documented disease progression, death, or start of new anti-cancer therapy for target lesions and assessed by CT/MRI.

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

The best overall response according to iRECIST was defined as the best response from the start of study treatment until the first documented disease progression, death, or start of new anti-cancer therapy for target lesions and assessed by CT/MRI.

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

The best overall response according to iRECIST was defined as the best response from the start of study treatment until the first documented disease progression, death, or start of new anti-cancer therapy for target lesions and assessed by CT/MRI. Stable disease according to iRECIST had to last at least 6 weeks from the start of study treatment. If not, at least 1 follow-up scan was required to declare stable disease.

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

The best overall response according to iRECIST was defined as the best response from the start of study treatment until the first documented disease progression, death, or start of new anti-cancer therapy for target lesions and assessed by CT/MRI.

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

The best overall response according to iRECIST was defined as the best response from the start of study treatment until the first documented disease progression, death, or start of new anti-cancer therapy for target lesions and assessed by CT/MRI.

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

Duration of response according to RECIST 1.1 was defined as time to disease progression for participants with partial response or complete response according to RECIST 1.1.

As outlined in the trial Protocol and Statistical Analysis Plan, patients were analyzed within pre-specified populations across the trial. There was no plan to analyze cohorts separately; results are presented in aggregate. The trial was a single-arm design, not a dose-escalation study; the RP2D (12 µg/kg) was established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort with one-way crossover to 12 µg/kg.

No participant had a PR or CR per RECIST; DoR data were not collected.

Duration of response according to iRECIST was defined as time to disease progression for participants with partial response or complete response according to iRECIST.

As outlined in the trial Protocol and Statistical Analysis Plan, patients were analyzed within pre-specified populations across the trial. There was no plan to analyze cohorts separately; results are presented in aggregate. The trial was a single-arm design, not a dose-escalation study; the RP2D (12 µg/kg) was established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort with one-way crossover to 12 µg/kg.

No participant had a PR or CR per iRECIST; DoR data were not collected

Clinical benefit rate according to RECIST 1.1 was defined as the number of partial responses, complete responses, and stable disease according to RECIST 1.1. Stable disease had to last at least 6 weeks from the start of study treatment. If not, at least 1 follow-up scan was required to declare stable disease. Participants with missing data were considered non-responders.

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

Clinical benefit rate according to iRECIST was defined as the number of partial responses, complete responses, and stable disease according to iRECIST. Stable disease had to last at least 6 weeks from the start of study treatment. If not, at least 1 follow-up scan was required to declare stable disease. Participants with missing data were considered non-responders.

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

Progression-free survival according to RECIST 1.1 was defined as the time from the first day of study treatment to the first date of radiological disease progression according to RECIST 1.1 or death.

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

Progression-free survival according to iRECIST was defined as the time from the first day of study treatment to the first date of radiological disease progression according to iRECIST or death.

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

Time to response according to RECIST 1.1 was defined as the time from the first day of study treatment to the first date of partial response or complete response according to RECIST 1.1. Participants with missing data were censored at the last assessment date, date of death, or date of eligibility (for incomplete or missing baseline tumor assessments), whichever occurred last.

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

Time to response according to iRECIST was defined as the time from the first day of study treatment to the first date of partial response or complete response according to iRECIST. Participants with missing data were censored at the last assessment date, date of death, or date of eligibility (for incomplete or missing baseline tumor assessments), whichever occurred last.

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

Time to progression according to RECIST 1.1 was defined as the time from the first day of study treatment to the first date of radiological disease progression according to RECIST 1.1.

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

Time to progression according to iRECIST was defined as the time from the first day of study treatment to the first date of radiological disease progression according to iRECIST.

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

A treatment-emergent adverse event is defined as an adverse event that started or worsened at or after the start of study treatment.

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

The following laboratory parameters will be assessed:

Coagulation: prothrombin time, activated partial thromboplastin time, international normalized ratio, D-dimer, and fibrinogen

Hematology: hemoglobin, glycated hemoglobin at screening, hematocrit, red blood cell count, reticulocytes, white blood cell count (with full differentiation), absolute lymphocyte count, and platelet count

Clinical chemistry: Na, K, Cl, phosphate, Mg, Ca, albumin, total protein, ALT, AST, bilirubin (direct, total), alkaline phosphatase, lactate dehydrogenase, creatinine clearance calculated by the Cockcroft-Gault formula, creatinine, glucose (preferably fasting), urea or blood urea nitrogen, cholesterol, triglyceride, C-reactive protein, uric acid, amylase, and lipase

Urinalysis: pH, glucose, protein, bilirubin, urobilinogen. Microscopic examination (mandated only if clinically indicated): red blood cell count, white blood cell count, epithelial cells, bacteria

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

The following vital signs parameters will be assessed:

Blood pressure (systolic and diastolic, after ≥5 minutes of rest), body temperature, and heart rate

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

Standard 12-lead electrocardiography was evaluated locally.

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

The following adverse events as per NCI CTCAE version 5.0 were considered dose-limiting toxicities:

• All grade 5 events not clearly related to disease progression or any other causes

• Any grade 3 or higher non-hematologic toxicity regardless of duration; exceptions:

  • Grade 3 nausea, vomiting, or diarrhea that could be controlled within 72 hours
  • Grade 3 fatigue lasting less than 5 days
  • Grade 3 or higher correctable electrolyte abnormalities lasting less than 72 hours and not associated with clinical complications
  • Grade 3 or higher serum amylase or lipase not associated with clinical manifestations of pancreatitis
  • Grade 3 AST or ALT increase or grade 3 blood bilirubin increase lasting 5 days or less

• Hy's law cases

• Hematologic DLTs:

  • Grade 4 decreased neutrophil count or decreased platelet count lasting more than 7 days
  • Febrile neutropenia
  • Grade 3 or higher decreased platelet count with bleeding

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

At 9 µg/kg nanrilkefusp alfa on Day 1 of Cycle 1

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

At 9 µg/kg nanrilkefusp alfa

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

At 9 µg/kg nanrilkefusp alfa

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

At 9 µg/kg nanrilkefusp alfa

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

At 9 µg/kg and 12 µg/kg nanrilkefusp alfa

Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.