F16IL2 in Combination With Nivolumab in Patients With Non-small Cell Lung Cancer

NCT05468294 | Unknown Phase 1

• 1 other identifier: PH-F16IL2PD1-01/16
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Prospective, open label, non-randomized, phase I/IIb study of F16IL2 in combination with Nivolumab.

Conditions

Non-small Cell Lung Cancer (NSCLC)

Outcome Measures

Primary Outcomes (4)

• Number of patients with adverse events that are related to treatment and classified as DLTs for each administered dosage - phase I study

  From Day 1 to Day 28 of treatment cycle

• Objective response rate (ORR) - phase II study

  At week 8

• Objective response rate (ORR) - phase II study

  At week 16

• Objective response rate (ORR) - phase II study

  At week 24

Secondary Outcomes (9)

• Human anti-fusion protein antibodies (HAFA) levels - phase I study

  1) at day 1; 2) at day 29; 3) at day 57; 4) at day 85; 5) at day 127; 6) at day 169;

• Objective response rate (ORR) - phase I study

  1) At day 52 - 56 (week 8) every 8 weeks up to 12 months; 2) At day 98 - 112 (week 16) every 8 weeks up to 12 months; 3) from week 24 every 12 weeks untils 12 months

• Progression-free survival (PFS) - phase I study

  1) At day 52 - 56 (week 8) every 8 weeks up to 12 months; 2) At day 98 - 112 (week 16) every 8 weeks up to 12 months; 3) from week 24 every 12 weeks untils 12 months

• Median overall survival (mOS) - phase I study

  From day 1 up to 1 year

• Percentage of Participants With On-Study Adverse Events (AEs) and Serious Adverse Events (SAEs) - phase II study

  From day 1 up to 1 year

Study Arms (1)

Ph I: F16IL2 + Nivolumab

EXPERIMENTAL

Patients will receive a fixed dose of Nivolumab and the following increasing dose levels of F16IL2: 15, 30, 50 and 70 Mio IU. Once the RD is established, 17 patients will receive a fixed dose of Nivolumab and F16IL2 at the RD, established during the Phase I part of the study.

Drug: F16IL2; Drug: Nivolumab, fixed dose

Interventions

F16IL2 DRUG

F16IL2 infusion will be always administered in 180 minutes i.v. on day 1, 8, 15 and 22 of each 28-days cycle.

Ph I: F16IL2 + Nivolumab

Nivolumab, fixed dose DRUG

Patients will receive 3 mg/kg of Nivolumab as a 60 minutes i.v. infusion on day 1 and day 15 of each 28-days cycle.

Ph I: F16IL2 + Nivolumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18-75 years.
• Subjects with histologically or cytologically-documented locally advanced NSCLC who present with stage IVA or IVB according to the 8th TNM classification. Pathological characterization must be sufficient to define patients as having either squamous or non-squamous histology.
• Previous treatment/s for NSCLC with platinum-based 1st line therapy regimen with or without maintainance therapy and documented disease progression. First line platinum-based therapy has to consist of at least 4 cycles.
• Patients with a known sensitizing mutation in the EGFR gene must have experienced disease progression (during or after treatment) or intolerance to treatment with afatinib, erlotinib, gefitinib, or another EGFR-TKI approved for the treatment of EGFR-mutant NSCLC. Patients with a known ALK fusion oncogene must have experienced disease progression (during or after treatment) or intolerance to treatment with crizotinib or another ALK-TKI approved for the treatment of NSCLC in patients having an ALK fusion oncogene.
• Evaluable tumor tissue available (either FFPE tissue block or unstained tumor tissue section); fresh or archival.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
• Patients must have at least one unidimensionally measurable lesion by computed tomography or MRIas defined by RECIST criteria 1.1.
• Prior radiation therapy is allowed, if the irradiated area is not the only source of measurable or assessable disease and if the radiation therapy is not within 4 weeks of the administration of study treatment.
• All acute toxic effects (excluding alopecia and fatigue) of any prior therapy (including surgery, radiation therapy, chemotherapy) must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v4.03) Grade ≤ 1.
• All baseline laboratory requirements will be assessed and should be obtained within 21 days of treatment start. Screening laboratory values must meet the following criteria:
• Absolute neutrophil count (ANC) ≥ 1.0 x 109/L, platelets ≥ 100 x 109/L, haemoglobin (Hb) ≥ 9.0 g/dl.
• Alkaline phosphatase (ALP), alanine aminotransferase (ALT) and or aspartate aminotransferase (AST) ≤ 3 x upper limit of reference range (ULN), and total bilirubin ≤ 2.0 mg/L unless liver involvement by the tumor, in which case the transaminase levels could be ≤ 5 x ULN.
• Creatinine ≤ 1.5 ULN or creatinine clearance ≥ 30 mL/min.
• Estimated life expectancy of at least 12 weeks.
• Negative serum pregnancy test for females of childbearing potential\*.

You may not qualify if:

• Any tumor therapy (chemotherapy, biologics for cancer, or an investigational therapy) within 4 weeks of the administration of study treatment.
• Uncontrolled tumor-related pain; patients requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated prior to enrollment.
• Active symptomatic central nervous system metastases. Subjects are eligible if CNS metastases have been treated and subjects have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 4 weeks prior to the first administration of study treatment.
• Subjects must have been either off corticosteroids, or on a stable or decreasing dose ≤ 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to enrollment.
• Carcinomatous meningitis
• Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study or any cancer curatively treated \< 5 years prior to study entry, except cervical carcinoma in situ, non-melanoma skin cancer, superficial bladder tumors.
• Pregnant and lactating women.
• Uncontrolled medical condition considered as high risk for the treatment with an investigational drug (e.g. unstable diabetes mellitus, vena-cava-syndrome, uncontrolled pleural effusion, pericardial effusion).
• Prior allogeneic bone marrow transplantation or solid organ transplant.
• Heart failure (\> Grade II, New York Heart Association Criteria - NYHA).
• History within the last 12 months of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
• Irreversible cardiac arrhythmias requiring permanent medication.
• History of stroke or transient ischemic attack within the previous 12 months.
• Severe or uncontrolled hypertension according to WHO criteria.
• Ischemic peripheral vascular disease (Grade IIb-IV).

Sponsors & Collaborators

• Philogen S.p.A.: lead

Study Sites (1)

Basel University Hospital

Basel, Switzerland

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2022
• First Posted: July 21, 2022
• Study Start: March 9, 2017
• Primary Completion: December 31, 2021
• Study Completion: July 1, 2022
• Last Updated: July 21, 2022

Record last verified: 2022-07

Locations

CH (1)