a dose escalation phase i study to assess the safety and clinical activity of multiple cancer indications

Conditions: Acute Myeloid Leukemia/Myelodysplastic Syndrome; Multiple Myeloma (MM)

Summary: think (therapeutic immunotherapy with nkr-2) is a multinational (eu/us) open-label phase i study to assess the safety and clinical activity of multiple administrations of autologous nkr-2 cells in seven refractory cancers, including five solid tumors (colorectal, ovarian, bladder, triple-negative breast and pancreatic cancers) and two hematological tumors (acute myeloid leukemia and multiple myeloma).

this open-label phase i study aims at assessing the safety and clinical activity of the nkr-2 treatment administered 3 times with a 2-week interval between each administration in different tumor types. in absence of progressive disease at the first tumor assessment following nkr-2 administratio, the patient will receive a new cycle of 3 administrations maximum with a 2-week interval. the study will contain two consecutive segments: a phase i dose escalation and a phase i expansion segment. the phase i dose escalation segment will include 2 arms, one in solid tumors and one in hematological tumors. the dose escalation design will include 3 dose levels: the dose escalation phase will consist of 3 cohorts (cohorts 1-3) for the solid tumors, and 3 cohorts (cohorts 4-6) for the hematological tumors; with each set of 3 cohorts receiving escalating doses of the nkr-2 therapy. two additional cohorts will be added in each dose escalation arm with the aim to provide a more intense treatment during the induction treatment. these additional cohorts in both the solid arm (cohort 8-9 - only in crc) and in the hematological arm of the study (cohort 10-11 - only in aml/mds) will therefore evaluate a tighter schedule of nkr-2 injections with the three first injections within the induction cycle separated by a 1-week interval followed two weeks later by a second cycle (cycle 2) with a 2-weeks interval between each three nkr 2 injections. these cohorts will each enroll 3 patients in case of no dlt. based on safety and early clinical data from these cohorts, the specific schedule of cohorts 8-11 might be selected for the expansion.

Eligibility criteria:
main inclusion criteria are: * men or women ≥ 18 years old at the time of signing the icf, * patient with a crc, epithelial ovarian cell or fallopian tube carcinoma, urothelial carcinoma, tnbc, pancreatic cancer, aml/mds or mm, * disease must be measurable according to the corresponding guidelines, * patient with an ecog performance status 0 or 1, and aml patients with anemia resulting in an ecog performance status of 2, * patient with adequate bone marrow reserve, hepatic and renal functions. * patients must have sufficient pulmonary functions with a forced expiratory volume in the first second (fev-1)/forced vital capacity (fvc) ≥ 0.7 with fev-1 ≥ 50% predicted. main exclusion criteria are: * patient with a tumor metastasis in the central nervous system, * patients who have received another cancer therapy within 2 weeks before the planned day for the apheresis (except hydroxyurea for aml patients), * patients who receive or are planned to receive any other investigational product within the 3 weeks before the planned day for the first nkr-2 administration (except hydroxyurea for aml patients), * patient is under systemic immunosuppressive drugs, unless specific cases authorized per protocol, * patients who have received other cell therapies, * patients who underwent major surgery within 4 weeks before the planned day for the first nkr-2 administration. * patient cannot present with history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis and/or active or acute exacerbation of chronic obstructive pulmonary disease (copd). detailed disease specific criteria exist and can be discussed with contacts listed below.