Study of ADXS-503 With or Without Pembro in Subjects With Metastatic Non-Small Cell Lung Cancer

NCT03847519 | Completed Phase 1 Results FDA Drug

• 1 other identifier: ADXS-503-101
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 9

Brief Summary

A Phase 1/2, Open-Label Study of ADXS-503 Alone and in Combination with Pembrolizumab in Subjects with Metastatic Squamous or Non-Squamous Non-Small Cell Lung Cancer

Conditions

Lung Cancer, Non-Small Cell; Metastatic Squamous Cell Carcinoma; Metastatic Non-Squamous Cell Carcinoma

Keywords

NSCLC Lung Cancer; Metastatic Squamous Non-Small Cell Lung Cancer; Metastatic Non-Squamous Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Safety/Tolerability of ADXS-503 Monotherapy in Part A and ADXS-503 With Pembrolizumab in Part B: Graded Per Comment Terminology Criteria for Adverse Events (CTCAE) Version 4.03

  The safety/tolerability of ADXS-503 monotherapy in Part A and in combination pembrolizumab in Part B was assessed by the number of patients with treatment-related adverse events.

  12 Months

• Preliminary Anti-tumor Activity of ADXS-503 + Pembrolizumab in Part C as Assessed by the Objective Response Rate (ORR)

  The anti-tumor activity of ADXS-503 + pembrolizumab was assessed by the objective response rate (ORR). The ORR according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 was defined as the number of participants with objective evidence of radiologic complete response (CR: the disappearance of all target lesions) and partial response (PR: at least 30% decrease in the sum of the longest diameters of target lesions compared with baseline, in absence of new lesions or unequivocal progression of non-target lesions) as determined from investigator response assessments. Disease Control Rates are based upon confirmed events only.

  3 years

Secondary Outcomes (2)

• Preliminary Anti-tumor Activity of ADXS-503 Alone in Part A and ADXS-503 With Pembrolizumab in Part B as Assessed by the Objective Response Rate (ORR)

  3 years

• Safety/Tolerability of ADXS-503 With Pembrolizumab in Part C: Graded Per Comment Terminology Criteria for Adverse Events (CTCAE) Version 4.03

  3 years

Study Arms (3)

Safety Phase Part A

EXPERIMENTAL

Enroll subjects with metastatic squamous or non-squamous NSCLC who have become refractory or intolerant to standard therapy. ADXS-503 monotherapy will be evaluated at 2 planned escalating dose levels: * Dose level 1: 1e8 CFU of ADXS-503, IV, every 3 weeks until disease progression, unacceptable toxicity, or another treatment discontinuation criterion is met. * Dose level 2: 5e8 CFU of ADXS-503, IV, every 3 weeks until disease progression, unacceptable toxicity, or another treatment discontinuation criterion is met.

Drug: ADXS-503

Safety Phase Part B

EXPERIMENTAL

Enroll subjects with metastatic squamous or non-squamous NSCLC. ADXS-503 will be evaluated at 2 planned escalating dose levels in combination with a fixed dose of pembrolizumab: * Dose level 1: 1e8 CFU of ADXS-503 + 200 mg of pembrolizumab, IV, every 3 weeks for up to 2 years or until disease progression, unacceptable toxicity, or another treatment discontinuation criterion is met. * Dose level 2: 5e8 CFU of ADXS-503 + 200 mg of pembrolizumab, IV, every 3 weeks for up to 2 years or until disease progression, unacceptable toxicity, or another treatment discontinuation criterion is met. (recruitment is on hold for this arm)

Drug: ADXS-503; Drug: Pembrolizumab

Efficacy Phase Part C

EXPERIMENTAL

Enroll subjects with metastatic squamous or non-squamous NSCLC. 1e8 CFU of ADXS-503 + 200 mg of pembrolizumab, IV, every 3 weeks for up to 2 years or until disease progression, unacceptable toxicity, or another treatment discontinuation criterion is met.

Drug: ADXS-503; Drug: Pembrolizumab

Interventions

ADXS-503 DRUG

A live attenuated Listeria monocytogenes (Lm)-based immunotherapy bioengineered to elicit T cell responses against shared tumor antigens commonly found in patients with squamous and non-squamous NSCLC.

Also known as: Lm immunotherapy, A503

Efficacy Phase Part C; Safety Phase Part A; Safety Phase Part B

Pembrolizumab DRUG

a programmed death receptor-1 (PD-1)- blocking antibody.

Also known as: Keytruda, pembro

Efficacy Phase Part C; Safety Phase Part B

Eligibility Criteria

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

You may qualify if:

• Subject and/or their legally authorized representative must be capable of understanding the investigational nature, potential risks, and benefits of the study. The subject and/or their legally authorized representative must sign a written informed consent;
• Subject is ≥18 years of age upon signing the Informed Consent Form;
• Subject has histologically or cytologically confirmed stage IV (metastatic) squamous or non-squamous NSCLC
• Part A only:
• ▪ Subject has received, and then progressed or been intolerant to up to 3 lines of prior therapy in the metastatic setting, including approved chemotherapy, targeted therapy, immunotherapy and antibody therapy, if eligible. Subjects who have received \>3 lines of prior therapy may be eligible for Part A, upon discussion with and approval by the Sponsor.
• Subjects will be eligible for Part A irrespective of PD-L1 expression.
• Subjects will be eligible for Part A irrespective of EGFR or ALK mutation status. However, subjects with an EGFR sensitizing mutation or ALK translocation must have received and then progressed or been intolerant to at least 1 prior line of approved targeted therapy to be eligible for Part A.
• Part B only:
• Subject is undergoing treatment with pembrolizumab monotherapy for metastatic NSCLC
• Subject's most recent tumor assessment is consistent with PD according to RECIST v1.1
• The Investigator has determined that PD should be confirmed within 4-8 weeks, and pembrolizumab treatment will continue pending PD confirmation
• Subject is willing to undergo a confirmatory scan 4-8 weeks from the prior scan that indicated progression on pembrolizumab
• There is no evidence of rapid disease progression or clinical deterioration in the subject that would preclude continuation of pembrolizumab treatment pending confirmation of PD.
• Part C only:
• Subject has received no prior systemic treatment in the metastatic setting. Subjects previously treated with adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 6 months prior to the diagnosis of metastatic disease.

You may not qualify if:

• Subject has an ongoing different primary malignancy. Exceptions include treated basal cell carcinoma of the skin or squamous cell carcinoma of the skin;
• Subject has an active autoimmune disease requiring systemic treatment within the past 3 months, a documented history of clinically severe autoimmune disease, or a disorder that requires systemic corticosteroids or immunosuppressive agents. Subjects with vitiligo, psoriasis, alopecia or resolved childhood asthma/atopy not requiring systemic treatment would be an exception to this rule. Subjects with hypothyroidism who are stable on hormone replacement (\>10 mg daily prednisone equivalent) or Sjögren's syndrome will not be excluded from the study;
• Subject has a diagnosis of primary immunodeficiency, is dependent on or has received systemic corticosteroid therapy (\>10 mg daily prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior to the first dose of study treatment. Inhaled or topical corticosteroids, and adrenal replacement corticosteroid doses \>10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease;
• Subject has neuropathy (sensory or motor) ≥Grade 3 per CTCAE v4.03;
• Subject has had an allogeneic tissue/solid organ transplant;
• Subject has interstitial lung disease (ILD) OR has had a history of pneumonitis that has required oral or IV steroids;
• Subject has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (no new or enlarging brain metastases) by imaging for at least 2 weeks following treatment, and clinically stable with no symptoms due to CNS metastasis, and are not using corticosteroids for at least 14 days prior to the start of study treatment;
• Subject has a concurrent unstable or uncontrolled medical condition (e.g., active uncontrolled systemic infection, unstable angina, congestive heart failure, uncontrolled diabetes) or other chronic disease, which in the opinion of the Investigator could compromise the subject or the study;
• Subject has a known history of human immunodeficiency virus (HIV) infection (HIV 1/2 antibodies);
• Subject has a known active hepatitis B (e.g., HBsAg reactive) or hepatitis C infection (e.g., HCV RNA \[qualitative\] is detected) or tuberculosis;
• Subject has an active infection requiring systemic therapy or is dependent on or currently receiving antibiotics that cannot be discontinued before dosing. (Note: Subjects who discontinue an antibiotic prior to dosing must wait at least 5 half-lives after the last dose of antibiotic before receiving any study treatment);
• Subject has known psychiatric or substance abuse disorder(s) that would interfere with cooperation with the requirements of the study;
• Subject has an implanted medical device that poses a high risk for bacterial colonization and/or that cannot be easily removed (e.g., prosthetic joints, artificial heart valves, pacemakers, orthopedic screws, metal plates, bone grafts, or other exogenous implants). NOTE: More common devices and prosthetics that include arterial and venous stents, dental and breast implants and venous access devices (e.g., Port-a-Cath or Mediport) are permitted. Sponsor must be contacted prior to consenting any subject who has any other device or implant;
• Subject is pregnant or breastfeeding, or plans to become pregnant or to father children, from the Screening visit through at least 120 days after the final dose of study treatment;
• Subject has a contraindication (e.g., sensitivity/allergy) to trimethoprim/ sulfamethoxazole and ampicillin;

Sponsors & Collaborators

• Advaxis, Inc.: lead

Study Sites (9)

City of Hope

Duarte, California, 91010, United States

Location

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Illinois CancerCare, P.C.

Peoria, Illinois, 61615, United States

Location

The University of Kansas Medical Center

Westwood, Kansas, 66205, United States

Location

Atlantic Health System, Carol G Simon Cancer Center

Morristown, New Jersey, 07960, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Providence Cancer Institute

Portland, Oregon, 97213, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Related Publications (1)

• A Phase 1/2, Open-Label Study of ADXS-503 Alone and in Combination with Pembrolizumab in Subjects with Metastatic Squamous or Non-Squamous Non-Small Cell Lung Cancer. Protocol ADXS-503-101, Advaxis Inc, 2018.

  BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell

Interventions

A 503; 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; Neoplasms, Squamous Cell

Results Point of Contact

• Title: Sumitra Sheeri
• Organization: Advaxis, Inc.

sheeri@advaxis.com

609-423-2528

Study Officials

• Surya Vangala

  Senior Director, Clinical Operations, Advaxis Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: Safety phase: * Part A: ADXS-503 monotherapy dose escalation * Part B: ADXS-503 + pembrolizumab dose escalation Efficacy phase: • Part C: ADXS-503 + pembrolizumab

Study Record Dates

• First Submitted: January 8, 2019
• First Posted: February 20, 2019
• Study Start: February 12, 2019
• Primary Completion: February 22, 2022
• Study Completion: February 22, 2022
• Last Updated: June 4, 2024
• Results First Posted: June 4, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)