Clinical trial NCT04735471: A Phase 1 Study of ADI-001 in B Cell Malignancies
Official title: A Phase 1 Safety and Efficacy Study of ADI-001 Anti-CD20 CAR-engineered Allogeneic Gamma Delta (γδ) T Cells in Adults With B Cell Malignancies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Lymphoma, Follicular
Lymphoma, Mantle-Cell
Marginal Zone Lymphoma
Primary Mediastinal B-cell Lymphoma
Diffuse Large B Cell Lymphoma
Lymphoma, Non-Hodgkin
Keywords: B-cell lymphoma
CAR-T
Cell Therapy
Allogeneic Cell Therapy
T cells, gamma delta
Immunotherapy, Adoptive
Antigens, CD20
Lead sponsor: Adicet Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-02-03
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 3+3 Dose Escalation Design
Primary purpose: TREATMENT

Brief summary: This is a Phase 1 dose escalation study following a 3+3 study design. The purpose of this study is to evaluate the safety and efficacy of ADI-001 in patients with B cell malignancies.

Detailed description: ADI-001 is an investigational immunotherapy composed of allogeneic gamma delta T cells that is being evaluated as a potential treatment for patients diagnosed with B cell malignancies who have relapsed or are refractory to at least two prior regimens. This first-in-human study will assess the safety and tolerability of ADI-001 and is designed to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD). Patients will be administered a single infusion or multiple infusions of ADI-001 cells. The study will include the following two parts:

Part 1 : dose escalation and extension. Parts 1a (escalation) and 1b (extension) will involve escalation and administration of single dose of ADI-001 and multiple doses of ADI-001.

Part 2 : dose expansion will involve dose administration of ADI-001 at MTD/MAD as determined in Part 1.

The study will also assess the pharmacokinetics and pharmacodynamics of ADI-001.

Eligibility criteria: Inclusion Criteria:

1. Relapsed/refractory (R/R) previously treated B cell malignancies.
2. Prior treatment must include at least 2 prior regimens, including anti CD20 antibody therapies. Prior Treatment with CD19 CAR T may be considered.
3. Documented measurable disease as defined by Lugano 2014
4. Male or female ≥ 18 years of age
5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
6. Adequate hematological, renal, pulmonary, cardiac, and liver function
7. Female patients who are not pregnant or breastfeeding
8. Female patients of childbearing potential and all male patients must agree to use highly effective methods of birth control for the duration of the study.

Exclusion Criteria:

1. Current or history of any of the following conditions:

   1. Central nervous system (CNS) primary lymphoma (current or history)
   2. Unrelated malignancy requiring systemic treatment (current or history \[in the past 3 years, other than hormonal treatment which is allowed\])
2. Any of the following current conditions:

   1. Active acute or chronic graft versus host disease (GvHD) other than grade 1 with skin involvement, or GvHD requiring immunosuppressive treatment within 4 weeks of enrollment
   2. Any other acute or chronic medical or psychiatric condition that may increase the risk associated with study participation or investigational product administration
   3. Tumor mass effects such as bowel obstruction or blood vessel compression that require therapy
   4. Opportunistic infections
3. History of any clinically significant conditions in the opinion of the Investigator
4. Prior treatment with any of the following:

   a Gene therapy, genetically modified cell therapy, or adoptive T cell therapy within 6 weeks of study enrollment.

   b Radiation therapy within 4 weeks prior to study entry. Palliative local radiation may be allowed within 1 week prior to study entry.

   c Autologous stem cell transplant (SCT) within 6 weeks of planned ADI 001 infusion.

   d Allogeneic transplant and donor lymphocyte infusion within 3 months of planned CAR T cell infusion
5. Patients unwilling to participate in an extended safety monitoring period (long term follow up \[LTFU\] protocol)

Primary outcomes:
measure: The Incidence of Subjects with Dose Limiting Toxicities within each dose level cohort
timeFrame: Day 28
measure: Proportion of treatment emergent and treatment related adverse events
timeFrame: 1 year
Secondary outcomes:
measure: Frequency and persistence of ADI-001
timeFrame: Day 1 through Month 12
measure: Overall Response Rate by Lugano Criteria
timeFrame: Day 28, Month 3, 6, 9, and 12
measure: Duration of Response
timeFrame: Day 28, Month 3, 6, 9, and 12
measure: Progression Free Survival
timeFrame: Day 28, Month 3, 6, 9, and 12
measure: Time To Progression
timeFrame: Day 28, Month 3, 6, 9, and 12
measure: Overall Survival
timeFrame: Day 28, Month 3, 6, 9, and 12
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Miami
country: United States
facility: University of Miami- Sylvester Comprehensive Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Northside Hospital Blood and Marrow Transplant Group of Georgia
state: Georgia
city: Iowa City
country: United States
facility: The State University of Iowa
state: Iowa
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Dallas
country: United States
facility: Baylor Scott &amp; White Research Institute
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Adicet Bio
name: Adicet Medical Director
role: STUDY_DIRECTOR
References:
citation: Nishimoto KP, Barca T, Azameera A, Makkouk A, Romero JM, Bai L, Brodey MM, Kennedy-Wilde J, Shao H, Papaioannou S, Doan A, Masri C, Hoang NT, Tessman H, Ramanathan VD, Giner-Rubio A, Delfino F, Sharma K, Bray K, Hoopes M, Satpayev D, Sengupta R, Herrman M, Abbot SE, Aftab BT, An Z, Panuganti S, Hayes SM. Allogeneic CD20-targeted gammadelta T cells exhibit innate and adaptive antitumor activities in preclinical B-cell lymphoma models. Clin Transl Immunology. 2022 Feb 2;11(2):e1373. doi: 10.1002/cti2.1373. eCollection 2022.