IDP-023 as a Single Agent and in Combination With Antibody Therapies in Patients With Advanced Hematologic Cancers

Study Overview
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Brief Summary
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This is an open label, Phase 1/2, first-in-human, multiple ascending dose, and dose-expansion study of IDP-023 administered as a single agent and in combination with or without interleukin-2 (IL-2), and with or without daratumumab or rituximab to evaluate the safety, tolerability and preliminary antitumor activity in patients with advanced hematologic cancers.

Detailed Description
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IDP-023 is an off-the-shelf, allogeneic cell product made of natural killer cells, also called NK cells. White blood cells are part of the immune system and NK cells are a type of white blood cell that are known to kill cancer cells. This is an open label, Phase 1/2, first-in-human, multiple ascending dose, and dose-expansion study of IDP-023 administered as a single agent and in combination with or without interleukin-2 (IL-2), and with or without daratumumab or rituximab to evaluate the safety, tolerability, and preliminary antitumor activity in patients with relapsed and/or refractory advanced multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL), respectively. The study is divided into a phase 1 dose escalation phase and a phase 2 expansion phase. Phase 1 (Escalation Phase): The primary objectives of Phase 1 are to define the safety of different IDP-023 containing regimens and to define the recommended regimen and Phase 2 doses (RP2D) of IDP-023. Phase 2 (Expansion Phase): The objective of the Phase 2 expansion cohort is to evaluate the safety and efficacy of IDP-023 in advanced MM in combination with daratumumab and advanced NHL in combination with rituximab.

Official Title
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Phase 1/2 Study of IDP-023 as a Single Agent and in Combination With Antibody Therapies in Patients With Advanced Hematologic Cancers

Conditions
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NHL, Multiple Myeloma, Blood Cancer, Refractory Non-Hodgkin Lymphoma, Relapsed Non-Hodgkin Lymphoma, Refractory Multiple Myeloma, Relapsed Multiple Myeloma

Intervention / Treatment
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* Drug: IDP-023
* Drug: Rituximab
* Drug: Daratumumab
* Drug: Interleukin-2
* Drug: Cyclophosphamide
* Drug: Fludarabine
* Drug: Mesna


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: For MM patients: Documented diagnosis of MM requiring systemic therapy and relapsed and/or refractory (R/R) disease after ≥ 3 prior lines of therapy. For NHL patients: R/R disease and failed ≥ 2 lines of systemic chemotherapy. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Life expectancy of greater than 12 weeks per the Investigator. Key Exclusion Criteria: Impaired cardiac function or history of clinical significant cardiac disease. Human immunodeficiency virus (HIV) infection, active hepatitis B infection, or hepatitis C infection. Active SARS-CoV-2 infection. Has untreated central nervous system, epidural tumor metastasis, or brain metastasis.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multiple ascending dose, and dose-expansion study of IDP-023 administered as a single agent and in combination with or without interleukin-2 (IL-2), and with or without daratumumab or rituximab.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1: Single Agent IDP-023 - Single Dose<br>NHL or MM patient treated with a single dose of IDP-023 monotherapy | Drug: IDP-023<br>* NK cell therapy<br>Drug: Cyclophosphamide<br>* Lymphodepleting chemotherapy<br>Drug: Fludarabine<br>* Lymphodepleting chemotherapy<br>Drug: Mesna<br>* Chemoprotectant<br>|
| Experimental: Phase 1: Single Agent IDP-023 - Multiple Doses<br>NHL and MM patients treated with multiple doses of IDP-023 monotherapy | Drug: IDP-023<br>* NK cell therapy<br>Drug: Cyclophosphamide<br>* Lymphodepleting chemotherapy<br>Drug: Fludarabine<br>* Lymphodepleting chemotherapy<br>Drug: Mesna<br>* Chemoprotectant<br>|
| Experimental: Phase 1: Single Agent IDP-023 - Multiple Doses with IL-2<br>NHL and MM patients treated with multiple doses of IDP-023 monotherapy | Drug: IDP-023<br>* NK cell therapy<br>Drug: Interleukin-2<br>* Immune cytokine<br>* Other names: Proleukin;Drug: Cyclophosphamide<br>* Lymphodepleting chemotherapy<br>Drug: Fludarabine<br>* Lymphodepleting chemotherapy<br>Drug: Mesna<br>* Chemoprotectant<br>|
| Experimental: Phase 2: Combination IDP-023 plus rituximab<br>NHL patients treated with multiple doses of IDP-023 in combination with rituximab | Drug: IDP-023<br>* NK cell therapy<br>Drug: Rituximab<br>* Anti-CD20 antibody therapy<br>* Other names: Rituxan;Drug: Interleukin-2<br>* Immune cytokine<br>* Other names: Proleukin;Drug: Cyclophosphamide<br>* Lymphodepleting chemotherapy<br>Drug: Fludarabine<br>* Lymphodepleting chemotherapy<br>Drug: Mesna<br>* Chemoprotectant<br>|
| Experimental: Phase 2: Combination IDP-023 plus daratumumab<br>MM patients treated with multiple doses of IDP-023 in combination with daratumumab | Drug: IDP-023<br>* NK cell therapy<br>Drug: Daratumumab<br>* Anti-CD38 antibody therapy<br>* Other names: Darzalex;Drug: Interleukin-2<br>* Immune cytokine<br>* Other names: Proleukin;Drug: Cyclophosphamide<br>* Lymphodepleting chemotherapy<br>Drug: Fludarabine<br>* Lymphodepleting chemotherapy<br>Drug: Mesna<br>* Chemoprotectant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) and serious adverse events (SAEs) - (Phase 1) | Escalation Period | 1 year | 
| Incidence of dose-limiting toxicities (DLTs) of IDP-023 Monotherapy - (Phase 1) | Escalation Period | up to 21 days | 
| Nature of dose-limiting toxicities (DLTs) of IDP-023 Monotherapy - (Phase 1) | Escalation Period | up to 21 days | 
| Incidence of dose-limiting toxicities (DLTs) of IDP-023 in combination with Daratumumab or Rituximab - (Phase 1) | Escalation Period | up to 35 days | 
| Nature of dose-limiting toxicities (DLTs) of IDP-023 in combination with Daratumumab or Rituximab - (Phase 1) | Escalation Period | up to 35 days | 
| Maximum tolerable dose (MTD) or a tolerated dose below MTD - (Phase 1) | Escalation Period | 1 year | 
| For MM: Anti-tumor activity by objective response rate (ORR), complete response (CR), stringent complete response (sCR), very good partial response (VGPR), and partial response (PR) - (Phase 2) | Expansion period | 2 years | 
| For NHL: Anti-tumor activity by objective response rate (ORR) - (Phase 2) | Expansion period | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK (Cmax) of IDP-023 - (Phase 1/2) | Escalation and expansion periods | 2 years | 
| PK (AUC) of IDP-023 - (Phase 1/2) | Escalation and expansion periods | 2 years | 
| For MM: Anti-tumor activity by objective response rate (ORR), complete response (CR), stringent complete response (sCR), very good partial response (VGPR), and partial response (PR) - (Phase 1) | Escalation period | 1 year | 
| For NHL: Anti-tumor activity by objective response rate (ORR) - (Phase 1) | Escalation period | 1 year | 
| Incidence of adverse events (AEs) and serious adverse events (SAEs) - (Phase 2) | Expansion period | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Hematologic Cancers