Infections

All Conditions

Symptoms and General Pathology

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Immune System Diseases

Rare Diseases

Communicable Diseases

Sarcoma

Acquired Immunodeficiency Syndrome

HIV Infections

Sarcoma, Kaposi

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Virus Diseases

Herpesviridae Infections

DNA Virus Infections

Neoplasms, Vascular Tissue

Soft Tissue Sarcoma

Kaposi Sarcoma

Patients receive efineptakin alfa IM on day 1. Cycles repeat every 9 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Efineptakin alfa

Chia-Ching (Jackie) Wang

This phase I trial studies the best dose and effects of NT-I7 in treating Kaposi sarcoma in patients with or without HIV. NT-I7 works by using a patient's immune system to fight cancer. It is made in a laboratory and is used to boost, direct, or restore the body's natural defenses against cancer. NT-I7 may work better in treating Kaposi sarcoma.

OUTLINE: This is a dose-escalation study.

Patients receive efineptakin alfa intramuscularly (IM) on day 1. Cycles repeat every 9 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up on day 30 (+/- 7 days) and then every 12 weeks for 12 months.

NT-I7 for Kaposi Sarcoma in Patients With or Without HIV

Phase 1 Study of NT-I7 (rhIL-7-hyFc) for the Treatment of Kaposi Sarcoma in Patients With or Without Infection With HIV

Measured by Common Terminology Criteria for Adverse Events version 5.0.

Will be assessed according to modified Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Group Criteria (ACTG) criteria.

Will be measured in subjects who obtain a partial response or better and defined as time from the best response within the first 36 weeks of therapy until disease progression or censoring. Kaplan Meier survival estimates will be constructed for each of these survival endpoints with 95% confidence intervals (CIs), for up to 1 year following initiation of treatment in all participants.

Kaplan Meier survival estimates will be constructed for each of these survival endpoints with 95% CIs, for up to 1 year following initiation of treatment in all participants.

The proportion of participants developing neutralizing antibodies will be summarized.

Cancer Immunotherapy Trials Network (CITN)

National Cancer Institute (NCI)

Fred Hutchinson Cancer Center

Recurrence

Glioblastoma

Astrocytoma

Gliosarcoma

Disease Attributes

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

BEFORE SURGERY: Patients receive pembrolizumab IV over 30 minutes and efineptakin alfa IM on day 1. Patients then undergo surgery 1 week later.

AFTER SURGERY: Patients receive pembrolizumab IV over 30 minutes and efineptakin alfa IM on day 1 of each cycle. Cycles repeat every 42 days for 2 years in the absence of disease progression or unacceptable toxicity.

Biospecimen Collection

Clinical Trials Referral Office

Jian L. Campian, M.D., Ph.D.

This phase II trial tests the safety and side effects of efineptakin alfa and pembrolizumab in treating patients with glioblastoma that has come back (recurrent). Efineptakin alfa is an immunotherapy drug that works by helping the immune system fight tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving efineptakin alfa and pembrolizumab may kill more tumor cells in patients with recurrent glioblastoma.

PRIMARY OBJECTIVE:

I. To determine the efficacy of pembrolizumab + efineptakin alfa (NT-I7) in combination with surgery in patients with recurrent glioblastoma multiforme (GBM) using the rate of overall survival at 9 months.

SECONDARY OBJECTIVES:

I. To assess progression-free survival in recurrent GBM patients treated with pembrolizumab + NT-I7 in combination with surgery.

II. To determine the objective response rate in recurrent GBM patients treated with pembrolizumab + NT-I7 in combination with surgery.

III. To assess changes in absolute lymphocyte counts (ALC) over time in recurrent GBM patients treated with pembrolizumab + NT-I7 in combination with surgery.

TERTIARY OBJECTIVES:

I. To assess the adverse event (AE) and toxicity profile of pembrolizumab + NT-I7 in combination with surgery in patients with recurrent GBM.

II. To assess the anti-glioma immune response in patients with recurrent GBM, before and after pembrolizumab and NT-I7 treatment, including assessment of cytokine profiling, immune cell phenotyping, function, and activation in the pre/post-treatment blood and tumor tissue when available.

III. To test tumor mutation burden on tumor/immune cells by validated comprehensive genomic profiling.

IV. To evaluate the changes for tumor microenvironment (TME) post pembrolizumab and NT-I7 and their correlations with treatment response and survival.

V. To evaluate tumor infiltrating lymphocytes (CD4, CD8, Treg, etc) in the tumor tissue pre- and post-treatment (when available).

VI. To assess changes in repertoire breadth and clonality by T-cell receptor (TCR) sequencing.

VII. To explore potential tissue and blood biomarkers that may predict response.

OUTLINE:

BEFORE SURGERY: Patients receive pembrolizumab intravenously (IV) over 30 minutes and efineptakin alfa intramuscularly (IM) on day 1. Patients then undergo surgery 1 week later.

AFTER SURGERY: Patients receive pembrolizumab IV over 30 minutes and efineptakin alfa IM on day 1 of each cycle. Cycles repeat every 42 days for 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and every 2-3 months until disease progression (if applicable), and then every 6 months for up to 5 years from study registration.

Efineptakin Alfa and Pembrolizumab for the Treatment of Recurrent Glioblastoma

Efficacy and Safety Study of Neoadjuvant Efineptakin Alfa (NT-I7) and Pembrolizumab in Recurrent Glioblastoma

9-month overall survival rate (OS9) rate is defined as the number of "successes" (patients who are alive at least 9 months after beginning study therapy) divided by the total evaluable patients. All patients who have signed a consent form, are eligible, and have begun treatment in Cycle 1 (first cycle of neo-adjuvant pembrolizumab + efineptakin alfa \[NT-I7\]) will be considered evaluable for the primary endpoint. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

Progression is defined according to Immunotherapy Response Assessment in Neuro-Oncology (iRANO) criteria. The median and 95% confidence intervals will be estimated using the Kaplan-Meier estimator.

Objective response rate (ORR) is defined as the number of responses achieved during treatment with pembrolizumab + NT-I7 in combination with surgery divided by the total number of evaluable patients. A patient will be deemed to have a response if complete response (CR) or partial response (PR) is achieved. Only patients with measurable disease documented on the post-operative baseline scan (prior to initiation of Cycle 2) will be considered evaluable for ORR. Point estimates will be generated for response rate with corresponding 95% binomial confidence intervals (Duffy and Santner).

Point estimates will be generated for the difference (at the magnitude of a fold-change) with corresponding 95% confidence intervals. All other changes in ALC over time will be exploratory and hypothesis generating. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

The number and severity of all adverse events will be tabulated and summarized in this patient population. Specifically, the overall percentages for Grade 3 or higher adverse events considered at least possibly related to treatment will also be calculated and reported. All other adverse event analysis will be exploratory and hypothesis generating. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

NeoImmune Tech

Merck Sharp & Dohme LLC

Mayo Clinic

Blood and Lymph Conditions

Lymphoma

Lymphoma, Follicular

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Follicular Lymphoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Tisagenlecleucel

Axicabtagene ciloleucel

CAR-T infusion administered per standard of care at Day 0 followed by NT-I7 on Day 21.

NT-I7 is administered via an intramuscular injection after CAR-T infusion on Day 21.

Administered as standard of care as described in the package insert on Day 0.

Lisocabtagene Maraleucel

Kristina Stermer, MMS

Elizabeth Budde, MD, PhD

Abhinav Deol

Armin Ghobadi, MD

Ahmed Galal, MD

This is a multicenter Phase 1b study evaluating the safety, tolerability, and preliminary anti-tumor activity of NT-I7 administration following standard of care CD19 CAR T-cell therapy for eligible subjects with r/r LBCL.

This is a multicenter Phase 1b study evaluating the safety, tolerability, and preliminary anti-tumor activity of NT-I7 administration following standard of care CD19 CAR T-cell therapy for eligible subjects with r/r LBCL. The study consists of a Dose Escalation phase followed by a Dose Expansion phase.

In the Dose Escalation phase, subjects will be enrolled in 1 of 7 dose levels, starting with 60 µg/kg and up to 720 µg/kg. A dose schedule for an individual dose level will not be taken into expansion until the Dose Escalation phase has been completed or a maximum tolerated dose (MTD) has been determined, whichever occurs first.

In the Dose Expansion phase, up to 15 subjects will be enrolled and treated with the recommended dose identified in the Dose Escalation phase.

Up to 17- 42 subjects in the Dose Escalation phase, and up to 15 subjects in the Dose Expansion phase will be enrolled at approximately 20 study centers.

Treatment Plan:

NT-I7 (aka rhIL-7-hyFc, efineptakin alpha), Tisagenlecleucel (Kymriah®), Axicabtagene ciloleucel (Yescarta®), Lisocabtagene Maraleucel (Breyanzi®)

\*CAR-T Therapy will be administered per manufacturer's recommendations and in accordance with FDA prescribing guidelines and best institutional practices for standard of care use.

Relapsed/Refractory Large B-cell Lymphoma With NT-I7 Post-CD19 CAR T-cell Therapy

A Phase 1b Study Evaluating the Safety, Tolerability and Preliminary Anti-tumor Activity of NT-I7 (Efineptakin Alfa) a Long-acting Human IL-7, Post-Kymriah® (Tisagenlecleucel), Post-Yescarta® (Axicabtagene Ciloleucel), or Post-Breyanzi® (Lisocabtagene Maraleucel) in Subjects With Relapsed/Refractory Large B-cell Lymphoma

According to NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0

DLT is defined as any AE occurring within the first 21 days after NT-I7 injection that is considered to be at least possibly, probably, or definitely related to the study treatment (NT-I7) per the investigator, and that meets at least one of the non-hematologic or hematologic criteria listed below.

The MTD will be defined as the dose of NT-I7 that yields a DLT rate ≤ 33%.

Determination of the RP2D: The RP2D will be based on an accumulation of all available data. All available data including clinical Pharmacokinetic, Pharmacodynamic, anti-tumor activity (including best overall response rate) and safety, and nonclinical pharmacology data will be pooled. Integrated dose-response and exposure-response analyses will be conducted to determine the RP2D

Duration of Response (DoR) for the responders defined as the time from the first occurrence of a documented objective response (Partial Response \[PR\] or Complete Response \[CR\]) to the time of the first documented disease progression or death from any cause, whichever occurs first, per the Lugano classification as determined by the investigator.

Progression Free Survival (PFS) defined as the time from the first study treatment (Day 1) to the first occurrence of progression or death from any cause, whichever occurs first, per the Lugano classification as determined by the investigator.

Overall survival (OS) defined as the time from first study treatment (Day 1) to death from any cause.

Grading of CRS will be based on American Society for Transplantation and Cellular Therapy (ASTCT) guidelines.

Grading of ICANS will be based on American Society for Transplantation and Cellular Therapy (ASTCT) guidelines.

NeoImmuneTech

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Oral Squamous Cell Carcinoma

Patients receive one dose of efineptakin alfa IM.

Angelica Valadez

Hyunseok Kang, MD

This phase I trial evaluates the side effects of NT-I7 in treating patients with squamous cell carcinoma of head and neck that has come back (recurrent) who are undergoing surgery. NT-I7 is an immunotherapy drug that works by helping the immune system fight tumor cells. The body produces T-cells which play an important role in body's immune response and its ability to recognize tumor cells. This immunotherapy drug may boost body's T-cells to help fight cancer and enhance body's response to cancer.

PRIMARY OBJECTIVE:

I. To evaluate safety and feasibility of a single intramuscular injection of efineptakin alfa (NT-I7) in patients with locally recurrent squamous cell carcinoma of head and neck (SCCHN).

SECONDARY OBJECTIVES:

I. To describe changes in absolute lymphocyte count (ALC) in peripheral blood after a single dose of NT-I7.

II. To describe changes in tumor infiltrating lymphocytes (TIL) in tumor microenvironment of surgical specimen after a single dose of NT-I7.

III. To evaluate changes in immune subsets in peripheral blood after a single dose of NT-I7 and after surgery.

EXPLORATORY OBJECTIVE:

I. To make assessment of exploratory biomarkers for pharmacodynamic activity of NT-I7 in peripheral blood, and/or tumor tissue.

OUTLINE:

Patients receive one dose of efineptakin alfa intramuscularly (IM).

After completion of study treatment, patients are followed up for 35 days after dose or 21 days after surgery.

NT-I7 for the Treatment of Recurrent Squamous Cell Carcinoma of Head and Neck Undergoing Surgery

A Window of Opportunity Trial of NT-I7 in Patients With Locally Recurrent Squamous Cell Carcinoma of Head and Neck (SCCHN) Undergoing Salvage Surgery

Gene expression profiling by bulk ribonucleic acid (RNA)-sequencing or single cell RNA sequencing will be performed.

Gene expression profiling by T cell receptor (TCR) diversity via TCR sequencing (TCRseq) will be performed.

Circulating cytokine analysis will be performed on serum samples.

The proportion of patients experiencing grade 3 or 4 adverse events assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be reported with exact binomial 95% confidence intervals. Safety analyses will be performed for all patients who receive a dose of NT-I7

Feasibility will be evaluated as the successful completion of pre-operative NT-I7 and proceeding to pre-planned surgery without any extended treatment-related delay defined as \> 28 days from day 15. A probability-based decision rule for the study will be used to decide if the probability of successfully proceeding to surgery as planned is convincingly less than .75

Descriptive changes in ALC in peripheral blood both before and after a single dose of NT-I7 will be recorded.

Descriptive changes in tumor infiltrating lymphocytes in tumour microenvironment (TME) after a single dose of NT-I7 in pre-treatment biopsy and surgical specimen will be recorded.

Descriptive changes in immune phenotyping in peripheral blood after a single dose of NT-I7 and after surgery as measured by mass cytometry will be recorded.

Principal Investigator

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Atezolizumab

Participants with no prior systemic therapy for advanced NSCLC will receive 1200 μg/kg NT-I7 IM on Day 1 and every 6 weeks and atezolizumab IV 1200 mg every 3 weeks until disease progression.

1200 μg/kg NT-I7 administered intramuscularly (IM) once every 6 weeks (Q6W) starting on Cycle 1. The treatment will be continued up to a maximum of 35 cycles (approximately 2 years).

efineptakin alfa

1200 mg atezolizumab administered intravenously (IV) once every 3 weeks (Q3W) starting on Cycle 1. The treatment will be continued up to a maximum of 35 cycles (approximately 2 years).

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.

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

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.

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.

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.

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.

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
NT-I7 for Kaposi Sarcoma in Patients With or Without HIV	NCT04893018	AIDS-Related Ka... HIV Infection Kaposi Sarcoma	Efineptakin alf...	18 Years -	Fred Hutchinson Cancer Center
Efineptakin Alfa and Pembrolizumab for the Treatment of Recurrent Glioblastoma	NCT05465954	High Grade Astr... Recurrent Gliob... Recurrent Glios...	Biospecimen Col... Efineptakin alf... Pembrolizumab	18 Years -	Mayo Clinic
Relapsed/Refractory Large B-cell Lymphoma With NT-I7 Post-CD19 CAR T-cell Therapy	NCT05075603	Refractory Diff... Refractory Diff... Recurrent Diffu... Refractory High... Refractory Tran...	Efineptakin alf... Tisagenlecleuce... Axicabtagene ci... Lisocabtagene M...	18 Years -	NeoImmuneTech
Relapsed/Refractory Large B-cell Lymphoma With NT-I7 Post-CD19 CAR T-cell Therapy	NCT05075603	Refractory Diff... Refractory Diff... Recurrent Diffu... Refractory High... Refractory Tran...	Efineptakin alf... Tisagenlecleuce... Axicabtagene ci... Lisocabtagene M...	18 Years -	NeoImmuneTech
NT-I7 for the Treatment of Recurrent Squamous Cell Carcinoma of Head and Neck Undergoing Surgery	NCT04588038	Recurrent Head ... Recurrent Hypop... Recurrent Laryn... Recurrent Oral ... Recurrent Oroph... Resectable Orop...	Efineptakin alf...	18 Years -	University of California, San Francisco
NT-I7 for the Treatment of Recurrent Squamous Cell Carcinoma of Head and Neck Undergoing Surgery	NCT04588038	Recurrent Head ... Recurrent Hypop... Recurrent Laryn... Recurrent Oral ... Recurrent Oroph... Resectable Orop...	Efineptakin alf...	18 Years -	University of California, San Francisco
NT-I7 for the Treatment of Recurrent Squamous Cell Carcinoma of Head and Neck Undergoing Surgery	NCT04588038	Recurrent Head ... Recurrent Hypop... Recurrent Laryn... Recurrent Oral ... Recurrent Oroph... Resectable Orop...	Efineptakin alf...	18 Years -	University of California, San Francisco
NT-I7 in Combination With Atezolizumab in Previously Untreated, PD-L1-expressing, Locally Advanced or Metastatic NSCLC	NCT04984811	Carcinoma, Non-... Non-Small Cell ... Non-Small Cell ... Nonsmall Cell L... Non Small Cell ...	efineptakin alf... Atezolizumab	18 Years -	NeoImmuneTech

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