A Phase 1b Study Evaluating the Safety, Tolerability and Preliminary Anti-tumor Activity of NT-I7 (Efineptakin Alfa) a Long-acting Human IL-7, Post-Kymriah® (Tisagenlecleucel), Post-Yescarta® (Axicabtagene Ciloleucel), or Post-Breyanzi® (Lisocabtagene Maraleucel) in Subjects With Relapsed/Refractory Large B-cell Lymphoma
Overview
- Phase
- Phase 1
- Intervention
- Efineptakin alfa
- Conditions
- Refractory Diffuse Large B-cell Lymphoma
- Sponsor
- NeoImmuneTech
- Enrollment
- 17
- Locations
- 4
- Primary Endpoint
- To determine the Maximum Tolerated Dose (MTD)
- Status
- Completed
- Last Updated
- 6 months ago
Overview
Brief Summary
This is a multicenter Phase 1b study evaluating the safety, tolerability, and preliminary anti-tumor activity of NT-I7 administration following standard of care CD19 CAR T-cell therapy for eligible subjects with r/r LBCL.
Detailed Description
This is a multicenter Phase 1b study evaluating the safety, tolerability, and preliminary anti-tumor activity of NT-I7 administration following standard of care CD19 CAR T-cell therapy for eligible subjects with r/r LBCL. The study consists of a Dose Escalation phase followed by a Dose Expansion phase. In the Dose Escalation phase, subjects will be enrolled in 1 of 7 dose levels, starting with 60 µg/kg and up to 720 µg/kg. A dose schedule for an individual dose level will not be taken into expansion until the Dose Escalation phase has been completed or a maximum tolerated dose (MTD) has been determined, whichever occurs first. In the Dose Expansion phase, up to 15 subjects will be enrolled and treated with the recommended dose identified in the Dose Escalation phase. Up to 17- 42 subjects in the Dose Escalation phase, and up to 15 subjects in the Dose Expansion phase will be enrolled at approximately 20 study centers. Treatment Plan: NT-I7 (aka rhIL-7-hyFc, efineptakin alpha), Tisagenlecleucel (Kymriah®), Axicabtagene ciloleucel (Yescarta®), Lisocabtagene Maraleucel (Breyanzi®) \*CAR-T Therapy will be administered per manufacturer's recommendations and in accordance with FDA prescribing guidelines and best institutional practices for standard of care use.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- •Subjects meeting any of the following criteria are not eligible for enrollment in the study:
- •In Dose Escalation phase: Grade ≥3 CRS or ICANS post-CD19 CAR T-cell infusion. Note: Grade 1 or 2 CRS or ICANs must be completely resolved \>3 days prior to NT-I7 injection
- •In Dose Expansion phase: Grade ≥3 CRS or ICANS post-CD19 CAR T-cell infusion. Note: Grade 1 or 2 CRS or ICANS must be completely resolved \>3 days prior to NT-I7 injection
- •Pregnant, lactating or breastfeeding or expecting to conceive or father children within the study duration from screening through 120 days after the last dose of study treatment.
- •This exclusion criteria has been removed and remains as a placeholder.
- •Subjects with documented current central nervous system (CNS) involvement by lymphoma are to be excluded from study participation.
- •Any concurrent chemotherapy or biologic or hormonal therapy for cancer treatment.
- •Note: Concurrent use of hormones for noncancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable. In addition, local treatment (eg, by local surgery or radiotherapy) of isolated lesions for palliative intent is acceptable beyond the DLT evaluation period with prior consultation and agreement with the medical monitor.
- •Subjects who have autoimmune disease history for the past 2 years, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. The following are exceptions to this criterion:
- •Subjects with vitiligo or alopecia.
Arms & Interventions
NT-I7 after CAR-T (Kymriah, Yescarta, or Breyanzi) infusion
CAR-T infusion administered per standard of care at Day 0 followed by NT-I7 on Day 21.
Intervention: Efineptakin alfa
NT-I7 after CAR-T (Kymriah, Yescarta, or Breyanzi) infusion
CAR-T infusion administered per standard of care at Day 0 followed by NT-I7 on Day 21.
Intervention: Tisagenlecleucel
NT-I7 after CAR-T (Kymriah, Yescarta, or Breyanzi) infusion
CAR-T infusion administered per standard of care at Day 0 followed by NT-I7 on Day 21.
Intervention: Axicabtagene ciloleucel
NT-I7 after CAR-T (Kymriah, Yescarta, or Breyanzi) infusion
CAR-T infusion administered per standard of care at Day 0 followed by NT-I7 on Day 21.
Intervention: Lisocabtagene Maraleucel
Outcomes
Primary Outcomes
To determine the Maximum Tolerated Dose (MTD)
Time Frame: 21 Days
The MTD will be defined as the dose of NT-I7 that yields a DLT rate ≤ 33%.
To determine the Recommended Phase 2 Dose (RP2D)
Time Frame: 21 Days
Determination of the RP2D: The RP2D will be based on an accumulation of all available data. All available data including clinical Pharmacokinetic, Pharmacodynamic, anti-tumor activity (including best overall response rate) and safety, and nonclinical pharmacology data will be pooled. Integrated dose-response and exposure-response analyses will be conducted to determine the RP2D
For Dose Escalation Phase: Incidence of adverse events (AE)
Time Frame: 21 Days
According to NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Incidence of Dose Limiting Toxicities (DLT)
Time Frame: 21 Days
DLT is defined as any AE occurring within the first 21 days after NT-I7 injection that is considered to be at least possibly, probably, or definitely related to the study treatment (NT-I7) per the investigator, and that meets at least one of the non-hematologic or hematologic criteria listed below.
Secondary Outcomes
- Rates of grade 3 and higher cytokine release syndrome (CRS)(Up to 3 months)
- Measurement of Overall Survival (OS)(up to 3 months)
- The effect of NT-I7 on CAR-T cells expansion by fluorescence-activated cell sorting (FACS)(Up to 3 months)
- Measurement of Duration of Response (DOR)(up to 3 months)
- Measurement of Progression-Free Survival (PFS)(up to 3 months)
- Rates of grade 3 and higher immune effector cell associated neurotoxicity syndrome (ICANS)(Up to 3 months)
- The effect of NT-I7 on CAR-T cells expansion by Quantitative DNA Polymerase Chain Reaction (PCR)(Up to 3 months)