Clinical trial NCT04673617: AB-101 as Monotherapy and With Immunotherapy in Patients With Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma
Official title: A Multi-Center, Open-Label, Phase 1/2 Clinical Trial to Evaluate the Safety and Anti-Tumor Activity of AB-101 Monotherapy and AB-101 With Immunotherapy in Patients With Relapsed/Refractory Non-Hodgkin Lymphoma of B-Cell Origin.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Non Hodgkin Lymphoma
Keywords: lymphoma
NHL
cell therapy
rituximab
NK cell
bendamustine
Lead sponsor: Artiva Biotherapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2020-12-17
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: AB-101 is an off-the shelf, allogeneic cell product made of "natural killer" cells, also called NK cells. White blood cells are part of the immune system and NK cells are a type of white blood cell that are known to kill cancer cells.

This clinical trial will enroll patients with relapsed/refractory non-Hodgkin lymphoma of B-cell origin and is conducted in two phases. The primary objectives of Phase 1 are as follows: 1) to evaluate the safety of AB-101 given alone or in combination with rituximab (including the DLBCL specific cohort) or in combination with bendamustine and rituximab; 2) to evaluate the potential clinical activity of AB-101 when given in combination with rituximab or in combination with bendamustine and rituximab (combination cohorts only); and 3) to identify the recommended Phase 2 dose (RP2D). The primary objective of Phase 2 is to determine whether AB-101 in combination with rituximab or in combination with bendamustine and rituximab has anti-cancer activity in patients.

Patients will be assigned to receive either AB-101 alone as monotherapy, in combination with rituximab (including DLBCL specific cohort) or in combination with bendamustine and rituximab. All patients will receive at least 1 treatment cycle of AB-101, followed by scheduled assessments of overall health and tumor response. Patients receiving AB-101 in combination with rituximab may receive up to 3 additional cycles of treatment. Patients receiving AB-101 in combination with bendamustine and rituximab may receive up to 5 additional cycles of treatment. Patients enrolled into the DLBCL specific cohort receiving AB-101 in combination with rituximab may receive up to 3 cycles of treatment.


Eligibility criteria: Inclusion Criteria:

* Confirmed diagnosis of aggressive NHL of B-cell origin. For enrollment into the DLBCL specific cohort: DLBCL, High-grade B-cell Lymphoma or PMBCL.
* Patient must have progressed or demonstrated intolerance to at least two lines of FDA-approved therapies, one of which must have included anti-CD20 monoclonal antibody therapy. The following are permitted: Prior autologous hematopoietic stem cell transplantation, prior treatment with FDA-approved CAR-T therapy, and/or prior treatment with an investigational agent. Prior treatment(s) with an FDA-approved CAR-T cell therapy or other cell therapies is permitted as long the patients are not considered to be refractory to this previous cell therapy approach (defined as progression within 120 days from the infusion of the cell therapy approach).
* Patient must have disease that allows for response assessment using the Lugano classification criteria.
* Ability to understand and sign the ICF.

Exclusion Criteria:

* Active CNS lymphoma or CNS involvement unless there is a history of at least 3 months of sustained remission of treated disease.
* History of clinically significant structural cardiac disease.
* Cardiac ejection fraction of \< 45% on echocardiogram or MUGA scan at screening assessment.
* Inadequate pulmonary function.
* History of a solid organ allograft, or an inflammatory or autoimmune disease likely to be exacerbated by IL-2.
* Ongoing uncontrolled systemic infections.
* Positive HIV PCR test
* Positive for Hepatitis B or Hepatitis C
* Prior allogeneic stem cell transplant.
* Females of childbearing potential must be willing and able to use appropriate contraception for duration of trial and for 6 months following final AB-101 dose. Males must be sterile or commit to using appropriate contraception until 90 days following the final dose of AB-101.
* Individuals who are pregnant or lactating are ineligible.
* Patients who received a previous genetically modified cell therapy product (e.g., CD19 CAR-T), and progressed within 120 days from the time of the cell therapy infusion

Primary outcomes:
measure: Phase 1: Safety and tolerability of AB-101 as monotherapy, and in combination with rituximab (including the DLBCL specific cohort) and in combination with bendamustine and rituximab.
timeFrame: From the ICF signature through 13 weeks after last study drug dose.
measure: Phase 1, combination therapy: AB-101 clinical activity, determined by ORR
timeFrame: From baseline disease assessment through end of study participation.
measure: Phase 1, combination therapy: Identify the recommended Phase 2 dose (R2PD) for AB-101.
timeFrame: From ICF signature through 13 weeks after last study drug dose.
measure: Phase 2: Determine the efficacy profile of AB-101 in combination with rituximab or in combination with bendamustine and rituximab when administered to patients with R/R NHL of B-cell origin.
timeFrame: From baseline disease assessment through end of study participation.
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Artiva Clinical Trial Site
state: Alabama
city: Tucson
country: United States
facility: Artiva Clinical Trial Site
state: Arizona
city: Orange
country: United States
facility: Artiva Clinical Trial Site
state: California
city: San Diego
country: United States
facility: Artiva Clinical Trial Site
state: California
city: Gainesville
country: United States
facility: Artiva Clinical Trial Site
state: Florida
city: Atlanta
country: United States
facility: Artiva Clinical Trial Site
state: Georgia
city: Chicago
country: United States
facility: Artiva Clinical Trial Site
state: Illinois
city: Iowa City
country: United States
facility: Artiva Clinical Trial Site
state: Iowa
city: Wichita
country: United States
facility: Artiva Clinical Trial Site
state: Kansas
city: Louisville
country: United States
facility: Artiva Clinical Trial Site
state: Kentucky
city: Detroit
country: United States
facility: Artiva Clinical Trial Site
state: Michigan
city: Lake Success
country: United States
facility: Artiva Clinical Trial Site
state: New York
city: New York
country: United States
facility: Artiva Clinical Trial Site
state: New York
city: Columbus
country: United States
facility: Artiva Clinical Trial Site
state: Ohio
city: Portland
country: United States
facility: Artiva Clinical Trial Site
state: Oregon
city: Philadelphia
country: United States
facility: Artiva Clinical Trial Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Artiva Clinical Trial Site
state: Pennsylvania
city: Providence
country: United States
facility: Artiva Clinical Trial Site
state: Rhode Island
city: Dallas
country: United States
facility: Artiva Clinical Trial Site
state: Texas
city: Salt Lake City
country: United States
facility: Artiva Clinical Trial Site
state: Utah
city: Richmond
country: United States
facility: Artiva Clinical Trial Site
state: Virginia
Study officials:
affiliation: Artiva Biotherapeutics
name: Subhashis Banerjee, M.D.
role: STUDY_DIRECTOR
References: