NT-I7 in Combination With Nivolumab in Advanced Gastric, Gastro-Esophageal Junction or Esophageal Adenocarcinoma

A Multicenter, Open-label, Phase 1 Dose Escalation ,Phase 2 Study of NT-I7 in Combination With Nivolumab in Subjects With Relapsed/Refractory Gastric or Gastro-Esophageal Junction or Esophageal Adenocarcinoma Who Progressed on or Intolerant to 2 or More Prior Lines of Systemic Therapy

The main purposes of the dose escalation part of this study is to determine the following in participants with gastric or gastro-esophageal junction (GEJ) or esophageal adenocarcinoma (EAC):

• Safety and tolerability of NT-I7 in combination with nivolumab
• Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RP2D)

The main purposes of Phase 2 of this study is to make a preliminary assessment of the antitumor activity and long-term survival of NT-I7 in combination with nivolumab in participants with gastric or GEJ or EAC.

Note, this trial was intended to be a Phase 1/2 trial (but the trial never moved forward to Phase 2).

Study Overview

• Status: Terminated
• Conditions: Gastric or Gastro-esophageal Junction (GEJ) or Esophageal Adenocarcinoma (EAC)
• Intervention / Treatment: Drug: NT-I7; Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Poland
  • Czestochowa, Poland, 42-202
    • Centrum Medyczne Klara
  • Skorzewo, Poland, 60-185
    • Pratia Poznań
• United States
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville James Graham Brown Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Texas
    • Fort Worth, Texas, United States, 76104
      • The Center for Cancer & Blood Disorders
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Dose Escalation: Have histologically or cytologically confirmed locally advanced or metastatic solid tumor and can be either CPI-pretreated or CPI-naive.

   Phase 2: Have histologically or cytologically confirmed locally advanced or metastatic carcinoma of Gastric or Gastro-Esophageal Junction (GEJ) or Esophageal Adenocarcinoma (EAC) and who progressed on or intolerant to 2 or more prior lines of standard therapy including chemotherapy, immunotherapy, and targeted therapy.

   Note: GEJ adenocarcinomas are defined as tumors that have their center within 5 cm proximal and distal of the anatomical cardia, as described in the Siewert classification system (Siewert et al, 2000).

2. Have at least one measurable lesion according to RECIST 1.1.
3. Participants enrolling in the dose escalation phase may have biopsiable disease. Optional for participants to provide a) pre-treatment tumor tissue sample and b) on-treatment tumor biopsy.
4. At least 20 participants enrolled in the Phase 2 must agree to provide tumor tissue sample prior to the start of treatment.
5. Female participants are either postmenopausal for at least 1 year, are surgically sterile for at least 6 weeks; if a female participant is of childbearing potential, she must agree to remain abstinent (refrain from heterosexual intercourse) or to follow instructions for one highly effective method of contraception for the duration of study treatment and for 5 months after the last dose of study treatment.
6. 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 follow instructions for one highly effective method of contraception for the duration of study treatment and for 3 months after the last dose of study treatment.

Exclusion Criteria:

1. Pregnant, or breastfeeding or expecting to conceive or father children within the study duration from screening through 5 months (for female participants) or 3 months (for male participants) after the last dose of study treatment.
2. Receiving chemotherapy or any anti-cancer therapy with half-life <1 week within 4 weeks or 5 half-lives, whichever is shorter, prior to first dose of study treatment.
3. Has received prior radiotherapy within 2 weeks of start of study treatment.
4. Has received treatment with complementary medications (excluding, herbal supplements, or traditional Chinese medications) to treat the disease under study within 2 weeks prior to the first dose of study treatment.
5. Subjects are eligible if CNS metastases are asymptomatic and do not require immediate treatment or have been treated and subjects have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment).
6. History of severe hypersensitivity reactions to monoclonal antibodies (mAbs) or intravenous immunoglobulin preparation.
7. Clinically significant cardiac disease.

8. Has a history of allergy or intolerance (unacceptable adverse events [AEs]) to study drug components or polysorbate-80-containing injections.

   Note: Polysorbate 80 is a buffer used to make NT-I7.

9. Has received a live vaccine within 4 weeks prior to the first dose of study drug. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed.
10. Has had an allogenic tissue/solid organ transplant or bone marrow transplant.
11. Subjects who were intolerable and discontinued from prior immune checkpoint inhibitors.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation; NT-I7 will be administered on Day 1 of alternate 4 weeks cycles (Cycle 1, 3, 5 etc.) (Q8W). Dosage will increase until the maximum tolerated dose (MTD) and/or the recommended phase 2 (RP2D) dose is reached. Nivolumab will be administered on Day 1 of every 4 week cycle (Q4W).	Drug: NT-I7; Administered by intramuscular (IM) injection.; Other Names: Efineptakin alfa; rhIL-7-hyFc; Drug: Nivolumab; Administered by intravenous (IV) injection.
Experimental: Phase 2: NT-I7 and Nivolumab; NT-I7 will be administered on Day 1 of alternate 4 weeks cycles (Cycle 1, 3, 5 etc.) (Q8W) at the recommended phase 2 dose (RP2D) identified during Dose escalation phase. Nivolumab will be administered on Day 1 of every 4 week cycle (Q4W).	Drug: NT-I7; Administered by intramuscular (IM) injection.; Other Names: Efineptakin alfa; rhIL-7-hyFc; Drug: Nivolumab; Administered by intravenous (IV) injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose escalation: Number of participants who experience one or more treatment-emergent adverse events (TEAEs)		Up to 1 year
Dose escalation: Number of participants who experience one or more common terminology criteria for adverse events (CTCAE) grade ≥ 3 adverse events		Up to 1 year
Dose escalation: Number of participants who experience one or more dose limiting toxicities (DLTs)		Up to 1 year
Dose escalation: Number of participants who experience one or more common terminology criteria for adverse events (CTCAE) grade ≥ 3 dose limiting toxicities (DLTs)		Up to 1 year
Phase 2: Objective response rate (ORR)	ORR is defined as the percentage of participants with a best overall response (BOR) of a complete response (CR) or partial response (PR), per RECIST 1.1.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DoR)	DOR is defined as the 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.	Up to 3 years
Disease control rate (DCR)	DCR is defined as the percentage of participants with a best overall response (BOR) of complete response (CR), partial response (PR), or stable disease (SD), per RECIST 1.1.	Up to 3 years
Progression free survival (PFS)	PFS is defined as the time from the first study treatment to the first occurrence of disease progression or death of any cause, whichever occurs first, per RECIST 1.1.	Up to 3 years
Phase 2: Overall survival (OS)	OS is defined as the time from first study treatment to death from any cause.	Up to 2 years
Number of participants with anti-drug antibodies (ADA) to NT-I7		Up to 3 years

Collaborators and Investigators

• Sponsor: NeoImmuneTech
• Collaborators: Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2021
• Primary Completion (Actual): May 26, 2023
• Study Completion (Actual): May 26, 2023

Study Registration Dates

• First Submitted: October 14, 2020
• First Submitted That Met QC Criteria: October 14, 2020
• First Posted (Actual): October 20, 2020

Study Record Updates

• Last Update Posted (Actual): August 16, 2024
• Last Update Submitted That Met QC Criteria: August 14, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Nivolumab; Dose escalation; NT-I7; Metastatic or Advanced
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Adenocarcinoma; Esophageal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: NIT-109; 2020-004175-41 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No