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

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.

Study Overview

• Status: Terminated
• Conditions: Solid Tumor; Peritoneal Cancer; Peritoneal Metastases
• Intervention / Treatment: Drug: Allocetra-OTS; Drug: Nivolumab; Drug: Tislelizumab

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Lior Binder; Phone Number: +972548054899; Email: lior@enlivexpharm.com

Study Locations

• Israel
  • Haifa, Israel
    • Rambam Medical Center
  • Jerusalem, Israel
    • Hadassah Medical Center
  • Ramat Gan, Israel
    • Sheba Medical Center
  • Tel Aviv, Israel
    • Sourasky Medical Center
• Spain
  • Madrid, Spain
    • Clinica Universidad de Navarra
  • Madrid, Spain
    • NEXT Madrid

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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.

2. Patients must have measurable disease.
3. Age ≥ 18 years old.
4. ECOG performance status ≤1.
5. Adequate renal function, hepatic function, and bone marrow function.

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stage 1 (Allocetra-OTS monotherapy); Dose escalation of Allocetra-OTS up to 10 x 10^9 cells by IV or IP administration.	Drug: Allocetra-OTS; 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.
Experimental: Stage 2.1 (Allocetra-OTS in combination with anti-PD-1 therapy); Dose escalation of Allocetra-OTS up to 10 x 10^9 cells by IV or IP administration, with IV nivolumab 240 mg.	Drug: Allocetra-OTS; 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.; Drug: Nivolumab; Immune checkpoint inhibitor (anti-PD-1 antibody)
Experimental: Stage 2.2 (Allocetra-OTS in combination with anti-PD-1 therapy); Dose escalation of Allocetra-OTS up to 10 x 10^9 cells by IV or IP administration, with IV tislelizumab 200 mg.	Drug: Allocetra-OTS; 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.; Drug: Tislelizumab; Immune checkpoint inhibitor (anti-PD-1 antibody)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	3-5 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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]).	12 months
Clinical benefit rate (CBR)	Clinical benefit rate (CBR) (percentage of patients who achieve best response of CR, PR or stable disease [SD]).	12 months
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.	12 months
Time to response (TTR)	Time to response (TTR), defined as the time to the first documented CR or PR.	12 months
Progression-free survival (PFS)	Progression-free survival (PFS), defined as the time to disease progression or death due to any cause.	12 months
Overall survival (OS)	Overall survival (OS) defined as the time to death due to any cause.	12 months

Collaborators and Investigators

• Sponsor: Enlivex Therapeutics RDO Ltd.
• Investigators: Principal Investigator: Roni Shapira, MD, Sheba Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2022
• Primary Completion (Actual): April 15, 2024
• Study Completion (Actual): April 15, 2024

Study Registration Dates

• First Submitted: October 12, 2022
• First Submitted That Met QC Criteria: October 12, 2022
• First Posted (Actual): October 14, 2022

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplastic Processes; Neoplasms; Neoplasm Metastasis; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Tislelizumab
• Other Study ID Numbers: ENX-CL-04-002a

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No