NT-I7 (Efineptakin Alfa) in Combination With Pembrolizumab in Participants With Advanced Solid Tumors

NCT ID: NCT04332653

Last Updated: 2026-02-09

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

215 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-06-10

Study Completion Date

2025-01-13

Brief Summary

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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 (R/R) tumors.

The main purpose of the Biomarker Cohort is to assess a potential correlation between tumor infiltrating lymphocytes (TILs) and clinical benefits in participants with CPI-naïve R/R ovarian cancer (OC).

Detailed Description

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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) and a Biomarker Cohort.

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) The Biomarker Cohort is designed to assess the correlation between tumor infiltrating lymphocytes (TILs) and clinical benefits of NT-I7 in combination with pembrolizumab in participants with CPI naïve R/R Ovarian Cancer (OC).

Conditions

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase 2a: CPI Naïve Microsatellite Stable Colorectal Cancer

Participants 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.

Group Type EXPERIMENTAL

NT-I7

Intervention Type DRUG

Administered by intramuscular (IM) injection

pembrolizumab (KEYTRUDA®)

Intervention Type DRUG

Administered by intravenous (IV) injection

Phase 2a: CPI Naïve Pancreatic Cancer

Participants 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.

Group Type EXPERIMENTAL

NT-I7

Intervention Type DRUG

Administered by intramuscular (IM) injection

pembrolizumab (KEYTRUDA®)

Intervention Type DRUG

Administered by intravenous (IV) injection

Phase 2a: CPI Naïve Microsatellite Stable Colorectal Cancer, Expansion Cohort

Participants with checkpoint inhibitor (CPI) naïve relapsed or refractory microsatellite stable colorectal cancer (MSS-CRC). Participants will receive 1200 µg/kg of NT-I7 and and a fixed dose of 200 mg of pemprolizumab.

Pembrolizumab will be administered on Day 1 of every 21 day cycle.

Group Type EXPERIMENTAL

NT-I7

Intervention Type DRUG

Administered by intramuscular (IM) injection

pembrolizumab (KEYTRUDA®)

Intervention Type DRUG

Administered by intravenous (IV) injection

Phase 2a: CPI Naïve Pancreatic Cancer, Expansion Cohort

Participants with checkpoint inhibitor (CPI) naïve relapsed or refractory pancreatic cancer (PC).Participants will receive 1200 µg/kg of NT-I7 and a fixed dose of 200 mg of pemprolizumab.

Pembrolizumab will be administered on Day 1 of every 21 day cycle.

Group Type EXPERIMENTAL

NT-I7

Intervention Type DRUG

Administered by intramuscular (IM) injection

pembrolizumab (KEYTRUDA®)

Intervention Type DRUG

Administered by intravenous (IV) injection

Biomarker Cohort: CPI Naïve Ovarian Cancer

Participants with checkpoint inhibitor (CPI) naïve relapsed or refractory ovarian cancer (OC). Participants will receive a starting dose of 960 µg/kg of NT-I7 and a fixed dose of 200 mg of pemprolizumab.

Pembrolizumab will be administered on Day 1 of every 21 day cycle.

Group Type EXPERIMENTAL

NT-I7

Intervention Type DRUG

Administered by intramuscular (IM) injection

pembrolizumab (KEYTRUDA®)

Intervention Type DRUG

Administered by intravenous (IV) injection

Phase 1b: NT-I7 Dose Escalation

NT-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.

Group Type EXPERIMENTAL

NT-I7

Intervention Type DRUG

Administered by intramuscular (IM) injection

pembrolizumab (KEYTRUDA®)

Intervention Type DRUG

Administered by intravenous (IV) injection

Phase 2a: CPI Treated Triple Negative Breast Cancer

Participants 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.

Group Type EXPERIMENTAL

NT-I7

Intervention Type DRUG

Administered by intramuscular (IM) injection

pembrolizumab (KEYTRUDA®)

Intervention Type DRUG

Administered by intravenous (IV) injection

Phase 2a: CPI Treated Non-small Cell Lung Cancer

Participants 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.

Group Type EXPERIMENTAL

NT-I7

Intervention Type DRUG

Administered by intramuscular (IM) injection

pembrolizumab (KEYTRUDA®)

Intervention Type DRUG

Administered by intravenous (IV) injection

Phase 2a: CPI Treated Small Cell Lung Cancer

Participants 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.

Group Type EXPERIMENTAL

NT-I7

Intervention Type DRUG

Administered by intramuscular (IM) injection

pembrolizumab (KEYTRUDA®)

Intervention Type DRUG

Administered by intravenous (IV) injection

Interventions

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NT-I7

Administered by intramuscular (IM) injection

Intervention Type DRUG

pembrolizumab (KEYTRUDA®)

Administered by intravenous (IV) injection

Intervention Type DRUG

Other Intervention Names

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Efineptakin alfa rhIL-7-hyFc KEYTRUDA®

Eligibility Criteria

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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, Arms I, IV, IVa, V, and Va of the Phase 2a, and the Biomarker Cohort OC 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).

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 and IVa: 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 and Va: 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.

Specific to Biomarker Cohort: CPI-naïve R/R Ovarian Cancer

* Up to 5 prior lines of treatment, including platinum-based treatment(s); participants treated previously with CPIs are not eligible.
* Willing to provide pre- and on-treatment tumor biopsies.

Exclusion Criteria

* Pregnant, lactating or breastfeeding.
* Receiving chemotherapy or any anti-cancer therapy (approved or investigational) with half-life \<1 week 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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp and Dohme LLC, Rahway, NJ, USA

UNKNOWN

Sponsor Role collaborator

NeoImmuneTech

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Moffit Cancer Center

Tampa, Florida, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Washington University School of Medicine in St. Louis

St Louis, Missouri, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Mary Crowley Cancer Research

Dallas, Texas, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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MK-3475-A60

Identifier Type: OTHER

Identifier Source: secondary_id

KEYNOTE-A60

Identifier Type: OTHER

Identifier Source: secondary_id

NIT-110

Identifier Type: -

Identifier Source: org_study_id

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