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

Phase 2TerminatedNCT04984811

NeoImmuneTech33 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (22)

University of South Alabama

Mobile, Alabama, United States

TOI Clinical Research

Cerritos, California, United States

Eastern CT Hematology & Oncology Associates

Norwich, Connecticut, United States

Florida Cancer Specialists - South Research Office

Fort Myers, Florida, United States

BRCR Medical Center

Plantation, Florida, United States

Florida Cancer Specialists - North Research Office

St. Petersburg, Florida, United States

Florida Cancer Specialists - East Research Office

West Palm Beach, Florida, United States

University Cancer and Blood Center

Athens, Georgia, United States

Goshen Center for Cancer Care

Goshen, Indiana, United States

Norton Cancer Institute

Louisville, Kentucky, United States

...and 12 more locations

Outcomes

Primary Outcomes

Objective Response Rate (ORR)

The percentage of subjects with a best overall response (BOR) of a complete response (CR) or partial response (PR), per RECIST 1.1 and iRECIST as determined by the investigator. Per RECIST v1.1, Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 mm. Furthermore, the appearance of one or more new lesions is also considered progression). Under iRECIST, tumor response is classified as immune Complete Response (iCR) or immune Partial Response (iPR) using the same size thresholds as RECIST 1.1.

Time frame: The first on-study imaging assessment were performed every 6 weeks for the first 6 months and every 9 weeks, or more frequently if clinically indicated, until disease progression or treatment discontinuation (up to 2 years).

Secondary Outcomes

Duration of Response (DoR)

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. Per RECIST v1.1, Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 mm. Furthermore, the appearance of one or more new lesions is also considered progression). Under iRECIST, tumor response is classified as immune Complete Response (iCR) or immune Partial Response (iPR) using the same size thresholds as RECIST 1.1.

Disease Control Rate (DCR)

The proportion of subjects with a best overall response of CR, PR or SD, per RECIST 1.1 and iRECIST as determined by the investigator.

Progression Free Survival (PFS)

The time from the first study 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. Progression is defined using RECIST 1.1 as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 mm. Furthermore, the appearance of one or more new lesions is also considered progression. Under iRECIST, initial progression is classified as immune unconfirmed progressive disease (iUPD). Progression is confirmed as immune confirmed progressive disease (iCPD) if a subsequent assessment (proportionately 4-8 weeks later) shows a further increase in tumor burden (an additional 5 mm increase in the sum of diameters of target or new lesions, or further progression of non-target lesions) or the appearance of additional new lesions.

Overall Survival (OS)

The time from first study treatment (Cycle 1, Day 1) to death from any cause.

Time frame: Up to 2 years