Date: 2016-04-20
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the American Association for Cancer Research (AACR) Annual Meeting
Company: National Cancer Institute (NCI) Juno Therapeutics (USA - WA)
Product: JCAR018
Action
mechanism: cell therapy/immunotherapy product/gene therapy/CAR-T cell therapy. JCAR018 is a CD22-specific CAR T cell therapy. CD22 is a cell surface protein expressed by most B cell malignancies, including NHL, ALL, and CLL. Juno Therapeutics has licensed this technology from Opus Bio. This product candidate was originally developed at the NCI. It has a fully human scFv and a 4-1BB costimulatory domain.
Disease: Follicular Lymphoma, ALL, NHL, Large Cell Lymphoma
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: In this study, researchers are using an anti-CD22 gene, a virus, and an immune receptor to change the cells. Objective: - To see if giving anti-CD22 Chimeric Antigen Receptor (CAR) cells to young people with certain cancers is safe and effective. Eligibility: - People ages 1 30 with a leukemia or lymphoma that has not been cured by standard therapy. Design: - Participants will be screened to ensure their cancer cells express the CD22 protein. They will also have medical history, physical exam, blood and urine tests, heart tests, scans, and x-rays. They may give spinal fluid or have bone marrow tests. - Participants may have eye and neurologic exams. - Participants will get a central venous catheter or a catheter in a large vein. - Participants will have white blood cells removed. Blood is removed through a needle in an arm. White blood cells are removed. The rest of the blood is returned by needle in the other arm. - The cells will be changed in a laboratory. - Participants will get two IV chemotherapy drugs over 4 days. Some will stay in the hospital for this. - All participants will be in the hospital to get anti-CD22 CAR cells through IV. They will stay until any bad side effects are gone. - Participants will have many blood tests. They may repeat some screening exams. - Participants will have monthly visits for 2-3 months, then every 3-6 months. They may repeat some screening exams. - Participants will have follow-up for 15 years. (NCT02315612 )
Latest
news: * On April 20, 2016, Juno Therapeutics announced, in partnership with its collaborators, early clinical data from two oral presentations for JCAR018 s at the American Association for Cancer Research (AACR) Annual Meeting 2016 in New Orleans, Louisiana. In an oral presentation, Terry J. Fry, M.D., Investigator, Pediatric Oncology Branch and Head of Hematologic Malignancies Section, National Cancer Institute, National Institutes of Health, presented “CD22 CAR Update and Novel Mechanisms of Leukemic Resistance.” Data from nine enrolled and treated patients were reported in this Phase I dose-escalation trial. As previously reported at the American Society of Hematology meeting in December 2015 (see below), six patients were treated at the lowest dose, with one patient achieving a complete remission and complete molecular remission as measured by flow cytometry. This patient relapsed after three months. * On December 6, 2015, Juno Therapeutics announced presentation of clinical data from a chimeric antigen receptor (CAR) T cell product candidate, JCAR018. In a poster presentation, Terry J. Fry, M.D. of the Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, presented “Clinical Activity and Persistence of Anti-CD22 Chimeric Antigen Receptor in Children and Young Adults with Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL).” Key takeaways include:
Three patients have enrolled at dose level 2 (1 x 106 cells/kg), which is in the dose range of CD19-directed CAR T programs. All three patients achieved a CR and CmR. These patients remain in complete remission with follow-up ranging from 3 to 6 months. The complete remissions have been seen in both patients naïve to CAR T therapies as well as those with CD19 negative relapse after prior CD19-directed CAR T therapy.
Limited cytokine release syndrome (CRS) was seen at dose level 2, with two patients at Grade 1 and one patient at Grade 2. No severe neurotoxicity was observed in these treatment cohorts. Dose limiting toxicity was observed at higher doses, so dosing continues at dose level 2 (1 x 106 cells/kg).
JCAR018 provides a potential treatment alternative to patients with CD19 epitope loss variants, particularly relevant in pediatric ALL.
In this Phase I dose-escalation trial, nine patients have enrolled and seven patients have been assessed to date.
Six patients were treated with the lowest dose (3 x 105 cells/kg), with one patient reaching MRD-negative CR, two patients having stable disease, and three patients having disease progression.
Three patients have enrolled at the next dose (1 x 106 cells/kg), which is in the dose range of CD19-directed CAR T programs. One patient achieved an MRD-negative CR, and two patients are too early to assess for response.
One patient at the lowest dose had Grade 3 diarrhea, and the maximum cytokine release syndrome was Grade 2.
