Clinical trial NCT04594811: NT-I7 in Combination With Nivolumab in Advanced Gastric, Gastro-Esophageal Junction or Esophageal Adenocarcinoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Gastric or Gastro-esophageal Junction (GEJ) or Esophageal Adenocarcinoma (EAC)
Keywords: NT-I7
Nivolumab
Dose escalation
Metastatic or Advanced
Lead sponsor: NeoImmuneTech
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2020-10-20
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Dose escalation: Number of participants who experience one or more treatment-emergent adverse events (TEAEs)
timeFrame: Up to 1 year
measure: Dose escalation: Number of participants who experience one or more common terminology criteria for adverse events (CTCAE) grade ≥ 3 adverse events
timeFrame: Up to 1 year
measure: Dose escalation: Number of participants who experience one or more dose limiting toxicities (DLTs)
timeFrame: Up to 1 year
measure: Dose escalation: Number of participants who experience one or more common terminology criteria for adverse events (CTCAE) grade ≥ 3 dose limiting toxicities (DLTs)
timeFrame: Up to 1 year
measure: Phase 2: Objective response rate (ORR)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Duration of response (DoR)
timeFrame: Up to 3 years
measure: Disease control rate (DCR)
timeFrame: Up to 3 years
measure: Progression free survival (PFS)
timeFrame: Up to 3 years
measure: Phase 2: Overall survival (OS)
timeFrame: Up to 2 years
measure: Number of participants with anti-drug antibodies (ADA) to NT-I7
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Louisville
country: United States
facility: University of Louisville James Graham Brown Cancer Center
state: Kentucky
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Fort Worth
country: United States
facility: The Center for Cancer & Blood Disorders
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Czestochowa
country: Poland
facility: Centrum Medyczne Klara
city: Skorzewo
country: Poland
facility: Pratia Poznań
Study officials:
References: