On October 24, 2024 Immunotherapy innovator ImmunityBio, Inc. (NASDAQ: IBRX), reported that the first patients have been dosed in an initial trial studying the potential of the company’s CAR-NK cell therapy targeting CD-19 in the treatment of non-Hodgkin’s lymphoma (NHL) (Press release, ImmunityBio, OCT 24, 2024, View Source [SID1234647367]). In the QUILT 106 trial, CD19-targeted high-affinity natural killer (t-haNK) cells are being tested initially as a single agent, and after demonstrating safety, then in combination with standard NHL treatment rituximab, in participants with selected CD19+ and CD20+ relapsed/refractory B-cell NHL. The phase 1, open label clinical study is designed to enroll up to 10 participants and is being conducted in Johannesburg, Pretoria, and Bloemfontein, South Africa.

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This is the first cellular-targeted natural killer (NK) cell therapy study ever to be conducted in South Africa, and is designed to provide important clinical information on a cancer with a significant rate of diagnosis in the region, but with few treatment options. Non-Hodgkin’s lymphoma is the 6th most common malignancy among people in Sub-Saharan Africa and it is the 4th most diagnosed cancer in men and the 5th most diagnosed cancer in women in South Africa, according to the Cancer Association of South Africa.

"This trial is important for ImmunityBio as our first clinical study of our CAR-NK, CD19 t-haNK cell line, as well as one of our first studies in liquid tumors," said Patrick Soon-Shiong, M.D., Executive Chairman, Founder and Global Chief Scientific and Medical Officer at ImmunityBio. "We have chosen to undertake this trial because Sub-Saharan African and, in particular, South African populations are often overlooked when it comes to advanced clinical research, despite the need for innovative immunotherapies in the region."

Full patient enrollment in this Phase 1 study of CD19 t-haNK is currently expected in the first quarter of calendar year 2025 with topline data readout expected in the second half of the calendar year 2025.

This study, being conducted in South Africa, is similar to ImmunityBio’s U.S.-based trial QUILT 3.092, a phase 1 open-label study of CD19 t-haNK as a single agent and in combination with the company’s IL-15 superagonist (N-803; ANKTIVA) and rituximab in participants with relapsed or refractory NHL.

About the QUILT 106 Study

The Phase 1, first-in-human (FIH), open-label study is designed to enroll up to 10 participants at sites in Johannesburg, Pretoria, and Bloemfontein, South Africa with the primary endpoint of the trial to evaluate the safety and preliminary efficacy of CAR-NK, CD19 t-haNK as a single agent and in combination with rituximab in participants with selected CD19+ and CD20+ R/R B-cell non-Hodgkin lymphoma (NHL). Participants will initially receive a single 3-week cycle of the CD19 t-haNK as a single-agent regime. Following a 1-week safety pause, participants will then receive a 3-week cycle of CD19 t-haNK in combination with rituximab. Patients will undergo multiple assessments of safety and efficacy to help evaluate the safety of CD19 t-haNK as a single agent and in combination with rituximab in participants with R/R NHL, who have active disease after completing ≥ 2 lines of cytotoxic chemotherapy.

About CAR-NK, CD19 t-haNK

CD19 t-haNK is a human, allogeneic, stable clonal NK cell line generated from the parental activated NK (aNK) cell line (NK-92). Based on the demonstrated therapeutic efficacy of chimeric antigen receptor (CAR) targeting and on the important role of FcγR-mediated antibody-dependent cellular cytotoxicity (ADCC) in the effectiveness of therapeutic IgG1 monoclonal antibodies, it was hypothesized that modification of the parental aNK cell line to stably express both a CD19-targeted CAR and the high-affinity variant of CD16 would result in potent and selective antitumor activity. Therefore, the novel CD19 t-haNK cells have been genetically engineered to stably express 3 main proteins: (1) a human CD19-targeted CAR; (2) the high-affinity variant of the human Fcγ receptor (FcγRIIIa/CD16a 158V) for enhanced ADCC; and (3) endoplasmic reticulum-retained version of human interleukin-2 (ERIL-2) for independent growth.

Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma (NHL) is a heterogeneous disease that most commonly originates in B lymphocytes. In 2020, according to the South Africa National Cancer Registry (SANCR 2020), it is estimated that 1 in 174 men and 1 in 288 women will develop NHL. According to Global Cancer Observatory (Sung 2021), the incidence of NHL is 4.1% of all cancers. A comparative study of the distribution of NHL subtypes in South Africa reported that Southern Africa had a significantly lower proportion of low-grade B cell NHL (34.3%) and a higher proportion of high-grade B cell NHL (51.5%) compared to Western Europe (54.5% and 36.4%) and North America (56.1% and 34.3%) (Perry 2015).