A Study of ADXS-NEO Expressing Personalized Tumor Antigens

NCT03265080 | Terminated Phase 1 FDA Drug

• 1 other identifier: ADXS-NEO-02
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 5

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).

Conditions

Colon Cancer Metastatic; Head and Neck Cancer Metastatic; Metastatic Non-Small Cell Lung Cancer; Urothelial Carcinoma; Metastatic Melanoma

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events

  From the first dose up to 20 months

• Maximum tolerated dose

  4 weeks

Secondary Outcomes (9)

• 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)

• DCR According to iRECIST

  Baseline to measured progressive disease or death due to any cause (approximately 15 months)

• Duration of Response (DoR) According to RECIST v1.1

  Baseline to measured progressive disease or death due to any cause (approximately 15 months)

Study Arms (3)

Part A

EXPERIMENTAL

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).

Biological: ADXS-NEO

Part B

EXPERIMENTAL

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.

Biological: ADXS-NEO; Biological: Pembrolizumab

Part C

EXPERIMENTAL

ADXS-NEO will be explored at 1 x 10\^8 CFU in combination with 200 mg of pembrolizumab in an expansion cohort.

Biological: ADXS-NEO; Biological: Pembrolizumab

Interventions

ADXS-NEO BIOLOGICAL

Intravenous infusion

Part A; Part B; Part C

Pembrolizumab BIOLOGICAL

Intravenous infusion

Part B; Part C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Screening tumor biopsy must be adequate for the identification of nonsynonymous somatic mutations (NSMs) by whole exome sequencing and for the development of ADXS-NEO. Biopsies may be repeated for participants whose Screening biopsies are found to be inadequate for the development of ADXS-NEO. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is generally inadequate.
• Participant population for Part A (ADXS-NEO monotherapy) is as follows:
• Histological or cytological diagnosis of metastatic colorectal cancer (CRC) excluding known microsatellite instability (MSI)-high sub-types, metastatic squamous cell carcinoma of head and neck (SCCHN) or metastatic non-small cell lung cancer (NSCLC) that have progressed or have become intolerant to standard therapy, and whose disease may allow management with other available therapies (or a treatment break, if appropriate) for up to approximately 12 weeks following Screening tumor biopsy. More than one form of anti-tumor therapy is allowed during this interval.
• For metastatic CRC, up to 4 lines of approved therapy in the advanced or metastatic setting are allowed, including approved antibody and targeted agent therapy. Participants may be eligible if they have received additional lines of therapy upon discussion with and approval by the Sponsor. Participants are excluded if they are known to have MSI-high tumors. If the status of microsatellite stability is not known, participants are eligible. The determination of microsatellite stability for CRC may be made by local testing on any available tissue prior to study entry.
• For metastatic SCCHN, up to 2 lines of approved therapy in the advanced or metastatic setting are allowed, including approved antibody therapy and immunotherapy if eligible. Participants may be eligible if they have received additional lines of therapy upon discussion with and approval by the Sponsor.
• For metastatic NSCLC, up to 3 lines of approved therapy in the advanced or metastatic setting are allowed, including approved antibodies, targeted agents and immunotherapy if eligible. Tumors harboring squamous and/or non-squamous histologies are eligible. Tumors harboring squamous and/or non-squamous histologies with neuroendocrine or small cell components may be eligible upon discussion with and approval by the Sponsor.
• Prior exposure to immunotherapy including, but not limited to, anti-PD1 or anti-Programmed death ligand-1 (PDL-1) antibodies is allowed but not required. Participants who received prior treatment with such agents must meet the following criteria: (a) Full resolution of prior checkpoint inhibitor-related adverse events and no treatment for these adverse events for at least 3 weeks prior to the first infusion of ADXS-NEO; and (b) no history of severe immune related adverse events (irAE) from prior exposure to checkpoint inhibitors. Severe irAEs are defined as any Common Terminology Criteria for Adverse Events (CTCAE) Grade 4 toxicity requiring treatment with corticosteroids or Grade 3 toxicity requiring corticosteroid treatment (greater than 10 mg/day prednisone or equivalent dose) for greater than 12 weeks.
• Participant population for Part B and Part C (ADXS-NEO + pembrolizumab) is as follows:
• Histological or cytological diagnosis of NSCLC, SCCHN, urothelial carcinoma, or melanoma.
• Participant has received, and then progressed or been intolerant to up to 3 lines of prior therapy in the advanced or metastatic setting, including approved chemotherapy, targeted therapy, immunotherapy and antibody therapy, if eligible. Participants who have received \>3 lines of prior therapy may be eligible upon discussion with and approval by the Sponsor.
• For NSCLC: Participants with metastatic NSCLC whose tumors express PD-L1 (tumor proportion score \[TPS\] ≥1%) as determined by a Food and Drug Administration (FDA)-approved test are eligible, with disease progression on or after platinum-containing chemotherapy. Participants with estimated glomerular filtration rate (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to enrolment.
• For SCCHN: participants with recurrent or metastatic SCCHN with disease progression on or after platinum-containing chemotherapy are eligible.
• For urothelial carcinoma:
• Participants with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 \[Combined Positive Score (CPS) ≥10\] as determined by an FDA-approved test, or participants who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status, are eligible.

You may not qualify if:

• Has a newly diagnosed tumor and a curative treatment option or approved therapy is available.
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided that they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to first dose of ADXS-NEO (Part A) or pembrolizumab (Part B and Part C). If a participant does not meet these criteria, the participant may be eligible upon discussion and agreement between the Sponsor and Investigator based upon the participant's specific case.
• Any active autoimmune disease or a documented history of autoimmune disease, or history of a syndrome that required systemic steroids or immunosuppressive medications, except for participants with Grade ≤2 vitiligo or resolved childhood asthma/atopy or uncomplicated dermatitis.
• History of recently (within previous 12 months) active diverticulitis, symptomatic peptic ulcer disease, colitis, inflammatory bowel disease or any gastrointestinal diseases that, in the opinion of the Investigator and Sponsor's medical monitor would pose a risk to the participant safety.
• History of other active malignancy for \< 2 years prior to enrollment. Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cancer that has undergone potentially curative therapy or is felt by the Investigator to be at low risk for recurrence is allowed.
• History or evidence of cardiovascular risk including any of the following:
• History or evidence of clinically significant arrhythmias (ventricular fibrillation, ventricular tachycardia, supraventricular tachycardia, atrial tachycardia/flutter, atrial fibrillation with rapid ventricular response, second or third degree atrioventricular block, and sick sinus syndrome).
• Exception: Participants with controlled atrial fibrillation for \>30 days prior to enrollment are eligible. Controlled atrial fibrillation is defined as atrial fibrillation with no ventricular response which requires no change in medication/dosage or addition of new medication or hospital admission within 30 days prior to enrollment.
• History of acute coronary syndromes (e.g., myocardial infarction and unstable angina) and/or coronary angioplasty within 6 months prior to enrollment.
• History or evidence of Class ≥II congestive heart failure as defined by New York Heart Association (NYHA).
• Chronic hypertension (defined as a systolic blood pressure \>140 mm Hg and/or diastolic blood pressure \>90 mm Hg which cannot be controlled by anti-hypertensive therapy).
• Participants with intra-cardiac defibrillators.
• Abnormal cardiac valve morphology (Grade ≥2). Participants with grade 1 abnormalities can be entered on study. Participants with moderate valvular thickening should not be entered on study. History of arterial thrombosis (e.g., stroke or transient ischemic attack) in the past 3 months.
• Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the Screening visit(s) through 120 days after the last dose of study treatment.

Sponsors & Collaborators

• Advaxis, Inc.: lead

Study Sites (5)

Honor Health

Scottsdale, Arizona, 85258, United States

Location

UCLA

Los Angeles, California, 90404, United States

Location

Ochsner Clinic Foundation - Ochsner Cancer Institute

New Orleans, Louisiana, 70121, United States

Location

Atlantic Health System

Morristown, New Jersey, 07960, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Related Publications (3)

• Hecht JR, Sheeri S, Heyburn J, Parsi M , Gutierrez AA, Tsai F. Clinical and immunogenicity data of a personalized neoantigen-Listeria vaccine in cancer patients: preliminary results. IO Combinations 360. Philadelphia, PA 20 June 2019.

  RESULT

• Tsai F, Goldman JW, Kosoff R, Heyburn JW, Sands T, Sheeri S, Petit R, Gutierrez AA, Hecht JR. Safety and Immunogenicity of a Personalized Neoantigen-Listeria Vaccine in Cancer Patients. Frontiers in Cancer Immunotherapy, The New York Academy of Sciences, May 14-15, 2019,New York, NY

  RESULT

• Hecht JR, Goldman JW, Hayes S, Balli D, Princiotta MF, Dennie JG, Heyburn J, Sands T, Sheeri S, Petit R, Gutierrez AA, Tsai F. Safety and immunogenicity of a personalized neoantigen -Listeria vaccine in cancer patients. AACR Annual Meeting 2019.

  RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Carcinoma, Transitional Cell; Melanoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Personalized immunotherapy treatment design

Study Record Dates

• First Submitted: July 12, 2017
• First Posted: August 29, 2017
• Study Start: March 28, 2018
• Primary Completion: October 24, 2019
• Study Completion: November 12, 2020
• Last Updated: February 24, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)