NT-I7 in Combination With Atezolizumab in Previously Untreated, PD-L1-expressing, Locally Advanced or Metastatic NSCLC

A Multicenter, Open-label, Single-arm Phase II Study to Evaluate Anti-tumor Efficacy and Safety of NT-I7 in Combination With Atezolizumab in Subjects With Previously Untreated, PD-L1-expressing, Locally Advanced or Metastatic NSCLC

This is a multicenter, open-label, single-arm Phase II study to evaluate anti-tumor efficacy and safety of NT-I7 in combination with atezolizumab in subjects with PD-L1-expressing (TPS ≥ 1%), metastatic (Stage IV) or locally advanced squamous or non-squamous NSCLC who have not received prior systemic therapy in the metastatic or locally advanced setting. Eligible subjects must have measurable disease according to RECIST 1.1. This Phase II study will enroll up to 83 subjects.

The main purpose of this study is to assess the preliminary anti-tumor activity of NT-I7 in combination with atezolizumab in subjects with programmed cell death ligand 1 (PD-L1)-expressing (tumor proportion score [TPS] ≥ 1%), locally advanced or metastatic squamous or non-squamous non-small cell lung cancer (NSCLC) who have not received prior systemic therapy for locally advanced or metastatic disease. The primary objective is evaluated based on the objective response rate (ORR) as assessed by investigators using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and immune RECIST (iRECIST).

Secondary objectives include further evaluation of the anti-tumor activity and efficacy of the combination therapy based on the duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) per RECIST 1.1 and iRECIST. In addition, the safety and tolerability of NT-I7 will be evaluated.

One treatment cycle is defined as 21 days (3 weeks). Atezolizumab is administered at a dose of 1200 mg via intravenous (IV) infusion once every 3 weeks (Q3W) on Day 1 of each cycle. NT-I7 is administered at a dose of 1200 μg/kg via intramuscular (IM) injection once every 6 weeks (Q6W) on Day 1 of alternating cycles, starting on Cycle 1 Day 1. On days when both study drugs are administered, atezolizumab is given prior to NT-I7.

Each subject may participate for a maximum of 35 cycles (approximately 2 years) of study treatment. The last safety follow-up visit will occur 90 days after the last dose, meaning the total participant duration could be up to 27 months.

Inclusion Criteria:

• Have histologically or cytologically confirmed metastatic or locally advanced NSCLC, and have not received prior systemic therapy. Subjects with locally advanced disease must have Stage III NSCLC and are not candidates for surgical resection or definitive chemoradiation
• Tumor PD-L1 expression (TPS≥1%) as determined by PD-L1 22C3 immunohistochemistry local or central assay.
• Have measurable disease
• Agree to provide screening biopsy (or archival tissue) at screening to assess PD-L1
• ECOG 0-1
• Adequate hematologic and end organ function

Exclusion Criteria:

• Prior systemic anti-cancer therapy
• NSCLC with EGFR, or ALK, or BRAF or ROS or RED or other genomic tumor aberrations which have available therapy
• Prior radiotherapy within 2 weeks of start of study treatment
• Known active CNS metastasis or carcinomatous meningitis
• Severe reactions to mAbs or IV immunoglobulin preparations
• Autoimmune disease history in past two years