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

Non Hodgkin Lymphoma Clinical Trial

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04673617
• Other study ID #: AB-101-01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 29, 2021
• Est. completion date: November 2024

Study information

• Verified date: February 2024
• Source: Artiva Biotherapeutics, Inc.
• Contact: AB-101-01 Study Team
• Phone: 858-326-4684
• Email: ab-101-01-study-team[@]artivabio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 108
• Est. completion date: November 2024
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Non Hodgkin Lymphoma

Intervention

Drug:
• AB-101
NK cell therapy
• Rituximab
Anti-CD20 antibody therapy
• Interleukin-2
Immune cytokine
• Cyclophosphamide
Lymphodepleting chemotherapy
• Fludarabine
Lymphodepleting chemotherapy
• Bendamustine
Chemoimmunotherapy

Locations

Country	Name	City	State
United States	Blood and Marrow Transplant Group of Georgia at Northside Hospital	Atlanta	Georgia
United States	University of Alabama	Birmingham	Alabama
United States	Rush University Medical Center	Chicago	Illinois
United States	OhioHealth Research Institute	Columbus	Ohio
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	UF Health Shands Cancer Hospital	Gainesville	Florida
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Northwell Health/R. J. Zuckerberg Cancer Center	Lake Success	New York
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Weill Cornell Medicine	New York	New York
United States	University of California, Irvine	Orange	California
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Jefferson Health	Philadelphia	Pennsylvania
United States	Oregon Health Sciences Center	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Huntsman Cancer Institute, University of Utah	Salt Lake City	Utah
United States	University of California San Diego Moores Cancer Center	San Diego	California
United States	The University of Arizona Cancer Center - North Clinic	Tucson	Arizona
United States	Cancer Center of Kansas	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Artiva Biotherapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Based on incidence, severity, and dose relationship of AEs and serious AEs (SAEs)	From the ICF signature through 13 weeks after last study drug dose.
Primary	Phase 1, combination therapy: AB-101 clinical activity, determined by ORR	Objective response rate (ORR) is defined as the proportion of patients with a documented complete response or partial response (CR + PR) in the absence of earlier disease progression.	From baseline disease assessment through end of study participation.
Primary	Phase 1, combination therapy: Identify the recommended Phase 2 dose (R2PD) for AB-101.	R2PD will be determined based on safety and tolerability of AB-101 in combination with rituximab or in combination with bendamustine and rituximab.	From ICF signature through 13 weeks after last study drug dose.
Primary	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.	The efficacy profile will be determined by the ORR.	From baseline disease assessment through end of study participation.