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

NCT04594811 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: NIT-1092020-004175-41
• Study Type: interventional
• Target: 10
• Locations: 2 countries
• Sites: 6

Brief Summary

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).

Conditions

Gastric or Gastro-esophageal Junction (GEJ) or Esophageal Adenocarcinoma (EAC)

Keywords

NT-I7; Nivolumab; Dose escalation; Metastatic or Advanced

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (5)

• Duration of response (DoR)

  Up to 3 years

• Disease control rate (DCR)

  Up to 3 years

• Progression free survival (PFS)

  Up to 3 years

• Phase 2: Overall survival (OS)

  Up to 2 years

• Number of participants with anti-drug antibodies (ADA) to NT-I7

  Up to 3 years

Study Arms (2)

Dose escalation

EXPERIMENTAL

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; Drug: Nivolumab

Phase 2: NT-I7 and Nivolumab

EXPERIMENTAL

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; Drug: Nivolumab

Interventions

NT-I7 DRUG

Administered by intramuscular (IM) injection.

Also known as: Efineptakin alfa, rhIL-7-hyFc

Dose escalation; Phase 2: NT-I7 and Nivolumab

Nivolumab DRUG

Administered by intravenous (IV) injection.

Dose escalation; Phase 2: NT-I7 and Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Have at least one measurable lesion according to RECIST 1.1.
• 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.
• At least 20 participants enrolled in the Phase 2 must agree to provide tumor tissue sample prior to the start of treatment.
• 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.
• 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.

You may not qualify if:

• 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.
• 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.
• Has received prior radiotherapy within 2 weeks of start of study treatment.
• 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.
• 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).
• History of severe hypersensitivity reactions to monoclonal antibodies (mAbs) or intravenous immunoglobulin preparation.
• Clinically significant cardiac disease.
• 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.
• 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.
• Has had an allogenic tissue/solid organ transplant or bone marrow transplant.
• Subjects who were intolerable and discontinued from prior immune checkpoint inhibitors.

Sponsors & Collaborators

• NeoImmuneTech: lead
• Bristol-Myers Squibb: collaborator

Study Sites (6)

University of Louisville James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

The Center for Cancer & Blood Disorders

Fort Worth, Texas, 76104, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Centrum Medyczne Klara

Częstochowa, 42-202, Poland

Location

Pratia Poznań

Skorzewo, 60-185, Poland

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

efineptakin alfa; Nivolumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2020
• First Posted: October 20, 2020
• Study Start: January 21, 2021
• Primary Completion: May 26, 2023
• Study Completion: May 26, 2023
• Last Updated: August 16, 2024

Record last verified: 2024-04

Locations

US (4); PL (2)