On January 21, 2021 Kuur Therapeutics, the leading developer of off-the-shelf CAR-NKT cell immunotherapies for the treatment of solid and hematological malignancies, reported clinical updates for both the phase 1 GINAKIT2 study of KUR-501 (autologous GD2 CAR-NKT cells) being tested in patients with relapsed/refractory (R/R) neuroblastoma, and the phase 1 ANCHOR study of KUR-502 (off-the-shelf CD19 CAR-NKT cells) being evaluated in patients with R/R CD19 positive malignancies (Press release, Kuur Therapeutics, JAN 21, 2021, View Source [SID1234574184]). Complete responses and evidence of tumor homing have been observed in both trials, and the CAR-NKT cell therapy has been safe and well-tolerated.
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"We are very excited by these results, which help validate the biology and clinical activity of CAR-NKT cells. Although these are phase 1 studies and continue to recruit patients, we are pleased we have been able to demonstrate tumor homing, an important property of CAR-NKT cells, along with an excellent safety profile," said Kurt Gunter MD, Kuur Chief Medical Officer. "We are grateful to the patients and families for their participation in these studies and to the scientists and physicians at Baylor College of Medicine for their scientific leadership."
"We are encouraged by the evidence of clinical activity with an allogeneic approach, especially at such a low dose," said Dr. Carlos Ramos, Principal Investigator of the ANCHOR study, Professor of Medicine at the Center for Cell and Gene Therapy (CAGT) at Baylor College of Medicine, and member of the Dan L Duncan Comprehensive Cancer Center. "We look forward to advancing the program and treating additional patients."
In the GINAKIT2 study, out of ten evaluable patients and with escalation to a dose level (DL) of 1×108 cells/m2, one complete response (CR) and one partial response (PR) have been observed to date, with stable disease (SD) in three additional patients. The patient with the CR is notable in that a PR was observed after the initial 1×108 cells/m2 dose, and a subsequent single dose at the same level deepened the response to a CR. Tumor biopsies show CAR-NKT cells homing to the neuroblastoma tumor site at all dose levels. KUR-501 has so far demonstrated a promising safety profile, with only one case of grade two cytokine release syndrome (CRS) and no cases of immune effector cell-associated neurotoxicity syndrome (ICANS).
In the ANCHOR study, of the two evaluable lymphoma patients treated to date at the starting DL of 1×107 cells/m2, one patient has experienced a CR and the other a PR. The patient with a CR was initially observed to be in PR four weeks after infusion but subsequently converted to a CR without additional therapy. Biopsy of the patient’s lymph node prior to conversion to CR status revealed viable, allogeneic CD19 CAR-NKT cells. The patient with a PR had previously failed autologous CAR-T cell therapy. KUR-502 has so far demonstrated a promising safety profile with no CRS, no ICANS, and no evidence of graft versus host disease (GvHD).
"We are very pleased to be able to report the first complete response in a patient treated with an allogeneic engineered CAR-NKT cell therapy," said Kevin S. Boyle, Sr., Chief Executive Officer of Kuur. "The clinical activity and safety data from both clinical trials are encouraging for the potential of our innovative CAR-NKT cell platform to create effective therapies for cancer patients."
The trials are being conducted at Baylor College of Medicine (Kuur’s CAR-NKT cell platform partner), Houston Methodist Hospital and Texas Children’s Hospital.
About KUR-501
KUR-501 is an autologous product in which natural killer T (NKT) cells are engineered with a chimeric antigen receptor (CAR) targeting GD2, which is expressed on almost all neuroblastoma tumors. KUR-501 is also designed to address key limitations of current CAR immune cell therapies by secreting the cytokine IL-15, which has been shown in nonclinical studies to increase the persistence of CAR-NKT cells and improve their efficacy within the immunosuppressive tumor microenvironment. KUR-501 is being tested in a phase 1 GINAKIT2 clinical study (NCT03294954) in patients with R/R high-risk neuroblastoma. The KUR-501 development program is also designed to provide autologous proof-of-concept for CAR-NKT cells in solid tumors using a validated target and has extensive potential applications in the treatment of hematological and solid tumors.
About KUR-502
KUR-502 is built on Kuur’s next-generation CAR-NKT platform with novel engineering capabilities that harness and enhance the unique tumor-homing properties of NKT cells. The NKT cells used in Kuur’s CAR-NKT platform have an invariant T cell receptor that does not distinguish between self- and non-self tissues, making the cells unlikely to induce GvHD when given to another person. Preclinical data generated by Baylor College of Medicine indicate that while human CAR-T cells cause severe GvHD, CAR-NKT cells from the same donor do not.
The ANCHOR (NCT03774654) study is a phase 1, first-in-human, dose escalation evaluation of KUR-502 in adults with R/R CD19 positive malignancies including B cell lymphomas, acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL). The single-arm study will evaluate three dose levels with patients receiving lymphodepletion chemotherapy consisting of cyclophosphamide and fludarabine followed by infusion with KUR-502.
Patients with R/R CD19 positive malignancies have limited effective treatment options. While CD19-directed autologous CAR-T cells are now available for these patients, they are limited by delays to get treatment, a requirement for patient leukapheresis, and issues with inferior quality leukapheresis starting material due to prior treatment. Off-the-shelf KUR-502 is designed to overcome these limitations.
The ANCHOR study is being sponsored and conducted by Kuur’s collaborator, Baylor College of Medicine and is currently recruiting participants.