Clinical trial NCT03018405: A Dose Escalation Phase I Study to Assess the Safety and Clinical Activity of Multiple Cancer Indications
Official title: A Multi-national, Open-label, Dose Escalation Phase I Study to Assess the Safety and Clinical Activity of Multiple Administrations of NKR-2 in Patients With Different Metastatic Tumor Types (THINK - THerapeutic Immunotherapy With NKR-2)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia/Myelodysplastic Syndrome
Multiple Myeloma (MM)
Lead sponsor: Celyad Oncology SA
Sponsor class: INDUSTRY
First posted: 2017-01-12
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: The maximum number of patients to be enrolled is 146:

* 36 in the dose escalation segment (cohorts 1-6, 18 per arm),
* 24 in the additional cohorts 8-11 (12 per arm),
* 86 patients in the Phase I expansion segment (note that the analysis of this segment will also include a maximum of 12 additional patients from the dose escalation segment).
Primary purpose: TREATMENT

Brief 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).

Detailed description: 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.

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of NKR-2 infusion
timeFrame: 24 months
Secondary outcomes:
measure: Clinical activity of the treatment in each tumor type
timeFrame: 24 months
Other outcomes:
Locations:
city: Tampa
country: United States
state: Florida
city: Buffalo
country: United States
state: New York
city: Brussels
country: Belgium
city: Brussels
country: Belgium
city: Ghent
country: Belgium
Study officials:
affiliation: Celyad Oncology SA
name: Frédéric Lehmann, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lonez C, Verma B, Hendlisz A, Aftimos P, Awada A, Van Den Neste E, Catala G, Machiels JH, Piette F, Brayer JB, Sallman DA, Kerre T, Odunsi K, Davila ML, Gilham DE, Lehmann FF. Study protocol for THINK: a multinational open-label phase I study to assess the safety and clinical activity of multiple administrations of NKR-2 in patients with different metastatic tumour types. BMJ Open. 2017 Nov 12;7(11):e017075. doi: 10.1136/bmjopen-2017-017075.