A Study of ADXS-NEO Expressing Personalized Tumor Antigens

Phase 1

Terminated

• Conditions: Head and Neck Cancer Metastatic; Urothelial Carcinoma; Metastatic Melanoma; Metastatic Non-Small Cell Lung Cancer; Colon Cancer Metastatic
• Interventions: Biological: ADXS-NEO; Biological: Pembrolizumab

• Registration Number: NCT03265080
• Lead Sponsor: Advaxis, Inc.

Brief Summary

This is a Phase 1, open-label, multicenter study of ADXS-NEO administered alone and in combination with pembrolizumab in participants with select advanced or metastatic solid tumors. This study will be performed in 2 phases, a safety phase (Part A and Part B) and an efficacy phase (Part C).

Detailed Description

Mutation-derived tumor antigens, which are often unique to each participant's tumor, represent a new source of targets for cancer immunotherapy. These mutations, which arise during tumorigenesis, are expressed only by the tumor and, as such, may be recognized as newly formed antigens, or neoantigens, by the participant's T cells. The lack of expression of participant-specific tumor mutations in nonmalignant cells suggests that vaccines targeting these tumor mutations have a low risk of autoimmunity and may represent a safer therapeutic approach than many of those currently available. The development of a Listeria monocytogenes (Lm)-based vaccine that expresses these participant-specific tumor antigens and that activates tumor-killing T cells has the potential to be a highly effective form of immunotherapy. In addition, the Lm platform, because it mediates tumor control through multiple mechanisms, may exhibit more robust anti-tumor activity than other vaccine platforms. Thus, the targeting of participant-specific mutation-derived tumor antigens and the concurrent stimulation of host immunity provides a rational approach for boosting anti-tumor immunity, as monotherapy and in combination with anti-programmed cell death protein-1 (PD-1) inhibitors.

Study Timeline

• Study First Submitted: 2017-07-12
• Study First Submitted QC: 2017-08-28
• Study First Posted: 2017-08-29
• Study Start: 2018-03-28
• Primary Completion: 2019-10-24
• Study Completion: 2020-11-12
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-22
• Last Update Posted: 2023-02-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part B	Pembrolizumab	Two dose levels of ADXS-NEO will be explored (i.e., 1 x 10\^8 and 5 x 10\^8 CFU) in combination with 200 mg of pembrolizumab.
Part C	ADXS-NEO	ADXS-NEO will be explored at 1 x 10\^8 CFU in combination with 200 mg of pembrolizumab in an expansion cohort.
Part A	ADXS-NEO	Dose cohorts of 3 participants each will be treated. Initiation of dosing will be staggered by at least 4 weeks for participants in the first cohort, also known as intra-cohort staggering. Two dose levels of ADXS-NEO will be explored: 1 x 10\^9 and 1 x 10\^8 colony forming unit (CFU).
Part B	ADXS-NEO	Two dose levels of ADXS-NEO will be explored (i.e., 1 x 10\^8 and 5 x 10\^8 CFU) in combination with 200 mg of pembrolizumab.
Part C	Pembrolizumab	ADXS-NEO will be explored at 1 x 10\^8 CFU in combination with 200 mg of pembrolizumab in an expansion cohort.

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events	From the first dose up to 20 months
Maximum tolerated dose	4 weeks

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	Baseline to measured progressive disease or start of new anticancer therapy (approximately 15 months)
ORR According to immune Response Evaluation Criteria in Solid Tumors (iRECIST)	Baseline to measured progressive disease or start of new anticancer therapy (approximately 15 months)
Disease Control Rate (DCR) According to RECIST v1.1	Baseline to measured progressive disease or death due to any cause (approximately 15 months)
DOR According to iRECIST	Baseline to measured progressive disease or death due to any cause (approximately 15 months)
Progression Free Survival (PFS) According to RECIST v1.1	Baseline to measured progressive disease or death due to any cause (approximately 15 months)
Overall Survival	Baseline to death due to any cause (approximately 20 months)
Duration of Response (DoR) According to RECIST v1.1	Baseline to measured progressive disease or death due to any cause (approximately 15 months)
DCR According to iRECIST	Baseline to measured progressive disease or death due to any cause (approximately 15 months)
PFS According to iRECIST	Baseline to measured progressive disease or death due to any cause (approximately 15 months)

Trial Locations

Locations (5)

UCLA; 🇺🇸 Los Angeles, California, United States

Rutgers Cancer Institute of New Jersey; 🇺🇸 New Brunswick, New Jersey, United States

Atlantic Health System; 🇺🇸 Morristown, New Jersey, United States

Honor Health; 🇺🇸 Scottsdale, Arizona, United States

Ochsner Clinic Foundation - Ochsner Cancer Institute; 🇺🇸 New Orleans, Louisiana, United States