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

Phase 1

Terminated

• Conditions: Peritoneal Cancer; Solid Tumor; Peritoneal Metastases
• Interventions: Drug: Allocetra-OTS; Drug: Nivolumab; Drug: Tislelizumab

• Registration Number: NCT05581719
• Lead Sponsor: Enlivex Therapeutics RDO Ltd.

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.

Study Timeline

• Study First Submitted: 2022-10-12
• Study First Submitted QC: 2022-10-12
• Study First Posted: 2022-10-14
• Study Start: 2022-11-15
• Status Verified: 2024-04
• Primary Completion: 2024-04-15
• Study Completion: 2024-04-15
• Last Update Submitted: 2024-04-15
• Last Update Posted: 2024-04-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 14

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Stage 1 (Allocetra-OTS monotherapy)	Allocetra-OTS	Dose escalation of Allocetra-OTS up to 10 x 10\^9 cells by IV or IP administration.
Stage 2.2 (Allocetra-OTS in combination with anti-PD-1 therapy)	Allocetra-OTS	Dose escalation of Allocetra-OTS up to 10 x 10\^9 cells by IV or IP administration, with IV tislelizumab 200 mg.
Stage 2.1 (Allocetra-OTS in combination with anti-PD-1 therapy)	Allocetra-OTS	Dose escalation of Allocetra-OTS up to 10 x 10\^9 cells by IV or IP administration, with IV nivolumab 240 mg.
Stage 2.1 (Allocetra-OTS in combination with anti-PD-1 therapy)	Nivolumab	Dose escalation of Allocetra-OTS up to 10 x 10\^9 cells by IV or IP administration, with IV nivolumab 240 mg.
Stage 2.2 (Allocetra-OTS in combination with anti-PD-1 therapy)	Tislelizumab	Dose escalation of Allocetra-OTS up to 10 x 10\^9 cells by IV or IP administration, with IV tislelizumab 200 mg.

Primary Outcome Measures

Name	Time	Method
Safety of Allocetra-OTS	3-5 weeks	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

Name	Time	Method
Overall Response Rate (ORR)/Best Overall Response Rate (BORR)	12 months	Overall Response Rate (ORR)/Best Overall Response Rate (BORR) (percentage of patients who achieve best response of complete response \[CR\] or partial response \[PR\]).
Progression-free survival (PFS)	12 months	Progression-free survival (PFS), defined as the time to disease progression or death due to any cause.
Clinical benefit rate (CBR)	12 months	Clinical benefit rate (CBR) (percentage of patients who achieve best response of CR, PR or stable disease \[SD\]).
Duration of response (DoR)	12 months	Duration of response (DoR), defined as the time from first documented evidence of CR or PR until disease progression or death.
Overall survival (OS)	12 months	Overall survival (OS) defined as the time to death due to any cause.
Time to response (TTR)	12 months	Time to response (TTR), defined as the time to the first documented CR or PR.

Trial Locations

Locations (6)

Hadassah Medical Center; 🇮🇱 Jerusalem, Israel

Sourasky Medical Center; 🇮🇱 Tel Aviv, Israel

Clínica Universidad de Navarra; 🇪🇸 Madrid, Spain

NEXT Madrid; 🇪🇸 Madrid, Spain

Sheba Medical Center; 🇮🇱 Ramat Gan, Israel

Rambam Medical Center; 🇮🇱 Haifa, Israel