A Dose Escalation Phase I Study to Assess the Safety and Clinical Activity of Multiple Cancer Indications

Phase 1

• Conditions: Multiple Myeloma (MM); Acute Myeloid Leukemia/Myelodysplastic Syndrome
• Interventions: Biological: NKR-2 cells

• Registration Number: NCT03018405
• Lead Sponsor: Celyad Oncology SA

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.

Study Timeline

• Study Start: 2016-12
• Study First Submitted: 2017-01-10
• Study First Submitted QC: 2017-01-10
• Study First Posted: 2017-01-12
• Status Verified: 2018-11
• Last Update Submitted: 2019-09-18
• Last Update Posted: 2019-09-19
• Primary Completion: 2021-05
• Study Completion: 2021-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 146

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Solid Tumors	NKR-2 cells	The dose escalation arm for solid tumors will use a 3 +3 design to determine the maximum tolerated dose. Two additional cohorts will be added in this dose escalation arm with the aim to provide a more intense treatment during the induction treatment (cycle 1 of injection). Cohort cohort 8-9 ( only in CRC) will evaluate a tighter schedule of NKR-2 injections at 1x109 or potentially 3x109 NKR-2 per injection with the three first injections within the induction cycle (cycle 1) 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.
Hematological tumors	NKR-2 cells	The dose escalation arm for hematological tumors will use a 3 +3 design to determine the maximum tolerated dose. Two additional cohorts will be added in this dose escalation arm with the aim to provide a more intense treatment during the induction treatment (cycle 1 of injection). Cohort 10-11 (only in AML/MDS) will evaluate a tighter schedule of NKR-2 injections at 1x109 or potentially 3x109 NKR-2 per injection with the three first injections within the induction cycle (cycle 1) 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.

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of NKR-2 infusion	24 months	Safety defined by Occurrence of adverse events (AEs) and serious adverse events (SAEs) during the study treatment until 30 days after the last study treatment administration.

Secondary Outcome Measures

Name	Time	Method
Clinical activity of the treatment in each tumor type	24 months	Clinical activity of the treatment in each tumor type