Clinical Trials /

NT-I7 (Hyleukin-7) in Combination With Pembrolizumab in Participants With Advanced Solid Tumors

NCT04332653

Description:

The main purposes of Phase 1b of this study are to determine the following in participants with advanced solid tumors: - Safety and tolerability of NT-I7 in combination with pembrolizumab - Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RP2D) The main purpose of Phase 2a of this study is to assess the preliminary anti-tumor activity of NT-I7 in combination with pembrolizumab in participants with checkpoint inhibitor (CPI) treated and naïve relapsed and refractory tumors.

Related Conditions:
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Pancreatic Carcinoma
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: NT-I7 (Hyleukin-7) in Combination With Pembrolizumab in Participants With Advanced Solid Tumors
  • Official Title: An Open-label Phase 1b/2a Study of NT-I7 (Hyleukin-7) in Combination With Pembrolizumab in Subjects With Relapsed/Refractory Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: NIT-110 (PNA60)
  • NCT ID: NCT04332653

Conditions

  • Any Advanced Solid Tumors
  • Triple Negative Breast Cancer
  • Non Small Cell Lung Cancer
  • Small Cell Lung Cancer
  • Microsatellite Stable Colorectal Cancer
  • Pancreatic Cancer

Interventions

DrugSynonymsArms
NT-I7Hyleukin-7, rhIL-7-hyFcPhase 1b: NT-I7 Dose Escalation
PembrolizumabPhase 1b: NT-I7 Dose Escalation

Purpose

The main purposes of Phase 1b of this study are to determine the following in participants with advanced solid tumors: - Safety and tolerability of NT-I7 in combination with pembrolizumab - Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RP2D) The main purpose of Phase 2a of this study is to assess the preliminary anti-tumor activity of NT-I7 in combination with pembrolizumab in participants with checkpoint inhibitor (CPI) treated and naïve relapsed and refractory tumors.

Detailed Description

      This is a multicenter, open-label Phase 1b/2a study of NT-I7 in combination with
      pembrolizumab. The study consists of a dose escalation phase (Phase 1b) followed by a dose
      expansion phase (Phase 2a).

      The Phase 1b is designed to assess the safety and tolerability, including determination of
      the Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RP2D) of NT-I7.

      The main purpose of Phase 2a of this study is to assess the preliminary antitumor activity of
      NT-I7 in combination with pembrolizumab in participants with relapsed/refractory

        -  checkpoint inhibitor (CPI)-treated Triple Negative Breast Cancer (TNBC), Non-small Cell
           Lung Cancer (NSCLC), and Small Cell Lung Cancer (SCLC)

        -  checkpoint inhibitor (CPI)-naïve Microsatellite Stable Colorectal Cancer (MSS-CRC), and
           Pancreatic Cancer (PC)
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1b: NT-I7 Dose EscalationExperimentalNT-I7 will be administered on Day 1 of alternate 21 day cycles (Cycle 1, 3, 5 etc.) Dosage will increase until the maximum tolerated dose (MTD) and/or the recommended phase 2 (RP2D) dose is reached. Pembrolizumab will be administered on Day 1 of every 21 day cycle.
  • NT-I7
  • Pembrolizumab
Phase 2a: CPI Treated Triple Negative Breast CancerExperimentalParticipants with checkpoint inhibitor (CPI) treated relapsed or refractory triple negative breast cancer (TNBC). Participants will receive the recommended phase 2 dose (RP2D) identified during Phase 1b. Pembrolizumab will be administered on Day 1 of every 21 day cycle.
  • NT-I7
  • Pembrolizumab
Phase 2a: CPI Treated Non-small Cell Lung CancerExperimentalParticipants with checkpoint inhibitor (CPI) treated relapsed or refractory non-small cell lung cancer (NSCLC). Participants will receive the recommended phase 2 dose (RP2D) identified during Phase 1b. Pembrolizumab will be administered on Day 1 of every 21 day cycle.
  • NT-I7
  • Pembrolizumab
Phase 2a: CPI Treated Small Cell Lung CancerExperimentalParticipants with checkpoint inhibitor (CPI) treated relapsed or refractory small cell lung cancer (SCLC). Participants will receive the recommended phase 2 dose (RP2D) identified during Phase 1b. Pembrolizumab will be administered on Day 1 of every 21 day cycle.
  • NT-I7
  • Pembrolizumab
Phase 2a: CPI Naïve Microsatellite Stable Colorectal CancerExperimentalParticipants with checkpoint inhibitor (CPI) naïve relapsed or refractory microsatellite stable colorectal cancer (MSS-CRC). Participants will receive the recommended phase 2 dose (RP2D) identified during Phase 1b. Pembrolizumab will be administered on Day 1 of every 21 day cycle.
  • NT-I7
  • Pembrolizumab
Phase 2a: CPI Naïve Pancreatic CancerExperimentalParticipants with checkpoint inhibitor (CPI) naïve relapsed or refractory pancreatic cancer (PC). Participants will receive the recommended phase 2 dose (RP2D) identified during Phase 1b. Pembrolizumab will be administered on Day 1 of every 21 day cycle.
  • NT-I7
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

        (Participants must meet all the following to be eligible)

          -  Participants with histologically or cytologically confirmed advanced or metastatic
             solid tumors.

          -  Have measurable disease per RECIST v1.1.

          -  Participants enrolling in the Phase 1b and Arms I, IV, and V of the Phase 2a must have
             biopsiable disease.

          -  Female participants who are either postmenopausal for at least 1 year, are surgically
             sterile for at least 6 weeks; female participants of childbearing potential must agree
             to remain abstinent (refrain from heterosexual intercourse) or to use dual methods of
             contraception for the duration of study treatment and for 120 days after the last dose
             of study treatment (pembrolizumab and/or NT-I7).

          -  Non-sterile male participants who are sexually active with female partners of
             childbearing potential must agree to remain abstinent (refrain from heterosexual
             intercourse) or to use highly effective method(s) of contraception for the duration of
             study treatment and for 120 days after the last dose of study treatment (pembrolizumab
             and/or NT-I7).

          -  Meet the requirements for the intended stages and arms (disease specific inclusion
             criteria), as following:

        Applicable to the Dose escalation phase (Phase 1b) only: (Biopsy Arm)

          -  Relapsed/refractory advanced solid tumors.

        Applicable to the Dose expansion phase (Phase 2a) only:

        Anti-PD-1/anti-PD-L1 refractory criteria for CPI-treated TNBC, NSCLC, and SCLC

          -  Has received at least 2 doses of an approved anti-PD-1/anti-PD-L1 monoclonal antibody
             (mAb).

          -  Has demonstrated disease progression after anti-PD-1/anti-PD-L1.

        Specific to Arm I: CPI-treated R/R TNBC (Biopsy Arm)

          -  Histopathologic or cytologic documented TNBC.

          -  Received one or more prior therapies for TNBC in the advanced or metastatic setting,
             and prior treatment (for advanced, metastatic or (neo) adjuvant).

        Specific to Arm II: CPI-treated R/R NSCLC

          -  Had prior treatment with CPI. Participants with estimated glomerular filtration rate
             (EGFR), BRAF, or c-ros oncogene 1(ROS1) mutations or anaplastic lymphoma kinase (ALK)
             translocations are required to have received prior therapy with the appropriate
             tyrosine kinase inhibitor (TKI).

        Specific to Arm III: CPI-treated R/R SCLC

          -  Recurrent extensive-stage SCLC; Received prior CPI therapy.

        Specific to Arm IV: CPI-naïve R/R MSS-CRC (Biopsy Arm)

          -  MSS-CRC (categorized as MSS by immunohistochemistry(IHC) or polymerase chain reaction
             (PCR).

          -  Previously treated with standard therapies, which must include fluoropyrimidine,
             oxaliplatin, and irinotecan; participants treated with CPI are not eligible.

        Specific to Arm V: CPI-naïve R/R Pancreatic Cancer (Biopsy Arm)

          -  Have documented radiographic progression to or documented in tolerance of first line
             systemic chemotherapy which included either gemcitabine or Fluorouracil (5-FU)-based
             regimen (including capecitabine);participants treated previously with CPI are not
             eligible.

        Exclusion Criteria:

          -  Pregnant, lactating or breastfeeding.

          -  Receiving any investigational therapy or any approved therapy for investigational use
             within 30 days or 5 half-lives.

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Participants with previously treated brain metastases may participate if
             stable.

          -  Participants who have received treatment with systemic immunosuppressive medications.

          -  Has a history of non-infectious pneumonitis that required steroids or current
             pneumonitis.

          -  Has had an allogenic tissue/solid organ transplant or bone marrow transplant.

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with
             an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,
             CTLA-4, OX-40, CD137) and was discontinued from that treatment due to a Grade 3 or
             higher Immune related adverse event (irAE).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1b: Safety and Tolerability of NT-I7 in Combination With Pembrolizumab to Determine the Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RP2D) of NT-I7
Time Frame:Up to 2 years
Safety Issue:
Description:Incidence, nature and severity of Adverse Events (AEs) graded according to NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 Incidence and nature of Dose-Limiting Toxicities (DLTs)

Secondary Outcome Measures

Measure:Duration of Objective Response (DOR)
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Disease Control Rate (DCR)
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Progression Free Survival (PFS)
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Number of Participants Who Experience an Increase in Anti-Drug Antibodies (ADAs) to NT-I7
Time Frame:Up to 2 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:NeoImmuneTech

Trial Keywords

  • NT-I7 (Hyleukin-7)
  • Solid Tumor
  • Pembrolizumab
  • Neoplasms
  • Lung
  • Breast
  • Pancreas
  • Colorectal
  • Non-small Cell Lung
  • Small Cell Lung
  • Thoracic Neoplasms
  • Interleukin 7
  • Carcinoma
  • Cancer
  • Programmed cell death protein (PD-1)

Last Updated

April 1, 2020