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A Phase 1/2a Study Evaluating Allocetra-OTS as Monotherapy or in Combination With Anti-PD-1 Therapy for the Treatment of Advanced Solid Tumor Malignancy

Primary Purpose

Solid Tumor, Peritoneal Metastases, Peritoneal Cancer

Status

Recruiting

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Allocetra-OTS

Nivolumab

Tislelizumab

About this trial

This is an interventional treatment trial for Solid Tumor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients must have histologically or cytologically confirmed locally advanced, unresectable or metastatic solid tumors, that have relapsed or have been refractory to available approved therapies, or patients who are not eligible for or declined additional standard of care systemic therapy.
Patients with peritoneal carcinomatosis can be eligible if an appropriate IP catheter or port can be placed.
Patients must have measurable disease.
Age ≥ 18 years old.
ECOG performance status ≤1.
Adequate renal function, hepatic function, and bone marrow function.

Exclusion Criteria:

Primary central nervous system (CNS) malignancy or CNS involvement, unless stable clinically.
Clinically significant uncontrolled infection, autoimmune or inflammatory diseases requiring systemic immunosuppression, clinically significant cardiovascular disease, severe pulmonary diseases or additional malignancies.
[For patients in Stage 2] Patients who previously experienced an ICI-related adverse reaction that resulted in discontinuation of the ICI.

Sites / Locations

Rambam Medical CenterRecruiting
Hadassah Medical CenterRecruiting
Sheba Medical CenterRecruiting
Sourasky Medical CenterRecruiting
Clínica Universidad de NavarraRecruiting
NEXT MadridRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Stage 1 (Allocetra-OTS monotherapy)

Stage 2.1 (Allocetra-OTS in combination with anti-PD-1 therapy)

Stage 2.2 (Allocetra-OTS in combination with anti-PD-1 therapy)

Arm Description

Dose escalation of Allocetra-OTS up to 10 x 10^9 cells by IV or IP administration.

Dose escalation of Allocetra-OTS up to 10 x 10^9 cells by IV or IP administration, with IV nivolumab 240 mg.

Dose escalation of Allocetra-OTS up to 10 x 10^9 cells by IV or IP administration, with IV tislelizumab 200 mg.

Outcomes

Primary Outcome Measures

Safety of Allocetra-OTS

Characterize the safety of Allocetra-OTS based on the dose-limiting toxicities (DLTs) of Allocetra-OTS as monotherapy or in combination with anti-PD1 therapy.

Secondary Outcome Measures

Overall Response Rate (ORR)/Best Overall Response Rate (BORR)

Overall Response Rate (ORR)/Best Overall Response Rate (BORR) (percentage of patients who achieve best response of complete response [CR] or partial response [PR]).

Clinical benefit rate (CBR)

Clinical benefit rate (CBR) (percentage of patients who achieve best response of CR, PR or stable disease [SD]).

Duration of response (DoR)

Duration of response (DoR), defined as the time from first documented evidence of CR or PR until disease progression or death.

Time to response (TTR)

Time to response (TTR), defined as the time to the first documented CR or PR.

Progression-free survival (PFS)

Progression-free survival (PFS), defined as the time to disease progression or death due to any cause.

Overall survival (OS)

Overall survival (OS) defined as the time to death due to any cause.

Full Information

NCT ID

NCT05581719

First Posted

October 12, 2022

Last Updated

June 19, 2023

Sponsor

Enlivex Therapeutics RDO Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT05581719

Brief Title

A Phase 1/2a Study Evaluating Allocetra-OTS as Monotherapy or in Combination With Anti-PD-1 Therapy for the Treatment of Advanced Solid Tumor Malignancy

Official Title

A Phase 1/2a Study Evaluating Allocetra-OTS as Monotherapy or in Combination With Anti-PD-1 Therapy for the Treatment of Advanced Solid Tumor Malignancy

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 15, 2022 (Actual)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Enlivex Therapeutics RDO Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

This is an open-label, non-randomized, multicenter, Phase 1/2a study to evaluate the safety and potential efficacy of Allocetra-OTS in the treatment of advanced solid tumor malignancy as monotherapy or in combination with an anti-PD-1 therapy.

Detailed Description

Despite the advent of novel targeted and immunotherapeutics for the treatment of solid tumors, many patients remain without cure. Allocetra-OTS is an immunomodulatory cell-based therapy consisting of allogeneic peripheral blood mononuclear cells that have been modified to be engulfed by macrophages and reprogram them into their homeostatic state. This is an open-label, non-randomized, multicenter, Phase 1/2a study to evaluate the safety and potential efficacy of Allocetra-OTS in the treatment of advanced solid tumor malignancy as monotherapy (Stage 1), and in combination with an anti-PD-1 therapy (Stage 2). Allocetra-OTS will be administered systemically or locally (intravenous [IV] or intraperitoneal [IP]) according to the tumor location.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Solid Tumor, Peritoneal Metastases, Peritoneal Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Stage 1 (Allocetra-OTS monotherapy)

Arm Type

Experimental

Arm Description

Dose escalation of Allocetra-OTS up to 10 x 10^9 cells by IV or IP administration.

Arm Title

Stage 2.1 (Allocetra-OTS in combination with anti-PD-1 therapy)

Arm Type

Experimental

Arm Description

Dose escalation of Allocetra-OTS up to 10 x 10^9 cells by IV or IP administration, with IV nivolumab 240 mg.

Arm Title

Stage 2.2 (Allocetra-OTS in combination with anti-PD-1 therapy)

Arm Type

Experimental

Arm Description

Dose escalation of Allocetra-OTS up to 10 x 10^9 cells by IV or IP administration, with IV tislelizumab 200 mg.

Intervention Type

Drug

Intervention Name(s)

Allocetra-OTS

Intervention Description

Allocetra-OTS is a cell-based therapy consisting of non-HLA matched allogeneic peripheral blood mononuclear cells, derived from a healthy human donor following a leukapheresis procedure, induced to an apoptotic stable state.

Intervention Type

Drug

Intervention Name(s)

Nivolumab

Intervention Description

Immune checkpoint inhibitor (anti-PD-1 antibody)

Intervention Type

Drug

Intervention Name(s)

Tislelizumab

Intervention Description

Immune checkpoint inhibitor (anti-PD-1 antibody)

Primary Outcome Measure Information:

Title

Safety of Allocetra-OTS

Description

Characterize the safety of Allocetra-OTS based on the dose-limiting toxicities (DLTs) of Allocetra-OTS as monotherapy or in combination with anti-PD1 therapy.

Time Frame

3-5 weeks

Secondary Outcome Measure Information:

Title

Overall Response Rate (ORR)/Best Overall Response Rate (BORR)

Description

Overall Response Rate (ORR)/Best Overall Response Rate (BORR) (percentage of patients who achieve best response of complete response [CR] or partial response [PR]).

Time Frame

12 months

Title

Clinical benefit rate (CBR)

Description

Clinical benefit rate (CBR) (percentage of patients who achieve best response of CR, PR or stable disease [SD]).

Time Frame

12 months

Title

Duration of response (DoR)

Description

Duration of response (DoR), defined as the time from first documented evidence of CR or PR until disease progression or death.

Time Frame

12 months

Title

Time to response (TTR)

Description

Time to response (TTR), defined as the time to the first documented CR or PR.

Time Frame

12 months

Title

Progression-free survival (PFS)

Description

Progression-free survival (PFS), defined as the time to disease progression or death due to any cause.

Time Frame

12 months

Title

Overall survival (OS)

Description

Overall survival (OS) defined as the time to death due to any cause.

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients must have histologically or cytologically confirmed locally advanced, unresectable or metastatic solid tumors, that have relapsed or have been refractory to available approved therapies, or patients who are not eligible for or declined additional standard of care systemic therapy. Patients with peritoneal carcinomatosis can be eligible if an appropriate IP catheter or port can be placed. Patients must have measurable disease. Age ≥ 18 years old. ECOG performance status ≤1. Adequate renal function, hepatic function, and bone marrow function. Exclusion Criteria: Primary central nervous system (CNS) malignancy or CNS involvement, unless stable clinically. Clinically significant uncontrolled infection, autoimmune or inflammatory diseases requiring systemic immunosuppression, clinically significant cardiovascular disease, severe pulmonary diseases or additional malignancies. [For patients in Stage 2] Patients who previously experienced an ICI-related adverse reaction that resulted in discontinuation of the ICI.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Lior Binder

Phone

+972548054899

lior@enlivexpharm.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Roni Shapira, MD

Organizational Affiliation

Sheba Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Rambam Medical Center

City

Haifa

Country

Israel

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ruth Perets, MD

Facility Name

Hadassah Medical Center

City

Jerusalem

Country

Israel

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Aron Popovtzer, MD

Facility Name

Sheba Medical Center

City

Ramat Gan

Country

Israel

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Roni Shapira, MD

Facility Name

Sourasky Medical Center

City

Tel Aviv

Country

Israel

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ravit Geva, MD

Facility Name

Clínica Universidad de Navarra

City

Madrid

Country

Spain

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Mariano Ponz Sarvisé, MD

Facility Name

NEXT Madrid

City

Madrid

Country

Spain

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Valentina Boni, MD

12. IPD Sharing Statement

Learn more about this trial

A Phase 1/2a Study Evaluating Allocetra-OTS as Monotherapy or in Combination With Anti-PD-1 Therapy for the Treatment of Advanced Solid Tumor Malignancy

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