AB-101 as Monotherapy and With Immunotherapy in Patients With Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma

Artiva Biotherapeutics

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

Non Hodgkin Lymphoma

Treatments

Drug: Rituximab

Drug: Cyclophosphamide

Drug: Fludarabine

Drug: AB-101

Drug: Bendamustine

Drug: Interleukin-2

Study type

Interventional

Funder types

Industry

Identifiers

NCT04673617

AB-101-01

Details and patient eligibility

About

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.

Enrollment

108 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

108 participants in 2 patient groups

Phase 1: Dose confirmation of AB-101 as mono, ritux combo (including DLBCL specific) & BR combo

Experimental group

Description:

Phase 1: Dose confirmation of AB-101 as monotherapy, in combination with rituximab (including the DLBCL specific cohort) and in combination with bendamustine and rituximab

Treatment: