Gamida Cell’s natural killer cell treatment is a promising approach to treat adults with relapsed or refractory non-Hodgkin’s lymphoma or multiple myeloma, according to early data from an ongoing Phase 1 clinical trial.
Data from the first 14 patients showed that the treatment was well-tolerated and eliminated cancer signs in three lymphoma patients and one myeloma patient.
The results were presented in the poster “First-in-Human Phase I Study of Nicotinamide-Expanded Related Donor Natural Killer Cells for the Treatment of Relapsed/Refractory Non-Hodgkin Lymphoma and Multiple Myeloma” at the 2019 Transplantation & Cellular Therapy (TCT) Meetings, Feb. 20-24 in Houston, Texas.
Natural killer cells are key players in the fight against tumors. But their insufficient numbers and short lifespan have limited their applicability as a treatment.
Gamida’s therapy is called NAM-expanded natural killer cells (NAM-NK). The approach increases the number of natural killer cells that can fight cancer by exposing them to a small molecule called nicotinamide, or NAM.
According to the company’s website, NAM-NK cells multiply faster, live longer, and are particularly good at producing inflammatory molecules and recruiting other immune cells into tumors than normal NK cells.
NAM-NK cells are being studied in an ongoing Phase 1 clinical trial (NCT03019666) as a treatment approach for non-Hodgkin’s lymphoma and multiple myeloma patients who have failed prior treatments.
Currently enrolling participants at the Masonic Cancer Center in Minnesota, the trial is out to recruit 24 patients ages 18–70. To enroll in the trial, non-Hodgkin’s lymphoma patients must produce the CD20 factor in their cancer cells and have failed conventional therapy, while myeloma patients must have received two previous lines of therapy.
Participants are first treated with a round of cyclophosphamide and fludarabine chemotherapy to deplete their body of immune cells, including diseased ones. They then receive escalating doses of NAM-NK cells and a short course of interleukin-2 to promote the killer cells’ expansion.
To help facilitate the cells’ toxic effect, lymphoma patients will receive Rituxan (rituximab) before and after they receive the cells. Myeloma patients will receive Empliciti (elotuzumab) instead of Rituxan.
The trial’s main objective is to assess the maximum dose that patients can tolerate. Secondary measures include how many patients respond to treatment and how long it takes before their disease progresses. Researchers will also study the treatment’s toxicity.
Researchers presented safety data from 14 patients, including six lymphoma patients and eight patients with myeloma, and efficacy data from 12 of these patients.
Overall, NAM-NK cells were generally well-tolerated, with no signs of graft versus host disease — when the transplanted cells attack the recipient’s body — neurotoxicity, or tumor lysis syndrome — when tumor cells shed their contents into the bloodstream, with potential life-threatening toxicity.
One patient developed cytokine release syndrome (CRS), a form of systemic inflammatory response causing flu-like symptoms, and one patient died due to generalized infection (sepsis).
Among the six lymphoma patients examined for efficacy, researchers reported three complete responses and one partial response. For the six myeloma patients, one achieved a complete response, and two experienced stable disease.
“I am encouraged by the emerging clinical profile of NAM-NK, and it is particularly exciting to witness complete responses in this heavily pretreated patient population. Following treatment, two of the patients who were in complete remission received a bone marrow transplant, which has curative potential,” Veronika Bachanova, MD, PhD, associate professor of Medicine at the University of Minnesota Medical School, said in a press release.
“I look forward to continuing to evaluate the potential of NAM-NK as the study progresses,” said Bachanova, who is also a member at the Masonic Cancer Center.
Gamida has also established a collaboration with Editas Medicine to use the gene-editing technology CRISPR to further enhance NAM-NK tumor-killing properties for both blood cancers and solid tumors.
“We are encouraged by the early data generated in the Phase 1 study of NAM-NK as an investigational therapy for patients with non-Hodgkin lymphoma and multiple myeloma, and we are pleased to have the opportunity to accelerate and broaden our NAM-NK research efforts through this agreement,” Julian Adams, PhD, chief executive officer of Gamida Cell, said in another press release.
“By leveraging the collective expertise of the Gamida Cell and Editas Medicine teams, we hope to enhance the efficacy of NAM-NK cells through CRISPR editing and potentially bring life-changing immunotherapy treatments to patients,” Adams said.
