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

Completed · Phase 1/Phase 2

Conditions studied: Lung Cancer, Non-Small Cell, Metastatic Squamous Cell Carcinoma, Metastatic Non-Squamous Cell Carcinoma

In brief

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

Key facts

Study ID

NCT03847519

Run by

Advaxis, Inc.

People needed

24

Starts

2019-02-12

Expected to finish

2022-02-22

Last updated by the study team

2024-06-04

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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.
• Subject has provided a formalin-fixed tumor sample from a biopsy of a tumor lesion either at the time of or after the diagnosis of metastatic disease AND from a site not previously irradiated, to assess for PD-L1 status. Biopsies obtained PRIOR to the administration of any systemic therapy to treat the subject's tumor (such as neoadjuvant/adjuvant therapy) will not be permitted for analysis. The tissue sample must be received by the central laboratory vendor prior to enrollment. Fine needle aspirates, Endobronchial Ultrasound (EBUS) or cell blocks are not acceptable. Needle or excisional biopsies, or resected tissue is required. If the tumor specimen is not evaluable for PD-L1 expression by the central laboratory, an additional tumor specimen may be submitted.
• Subject's tumor has PD-L1 expression of ≥50%, as determined by immunohistochemistry (IHC) at a central laboratory.
• Subject's tumor does not harbour an EGFR sensitizing (activating) mutation or ALK translocation. EGFR sensitizing mutations are mutations that are amenable to treatment with TKIs (e.g., erlotinib, gefitinib, afatanib, osimertinib). ALK translocations are amendable to treatment with TKIs such as crizotinib, alectinib and ceritinib. Investigators must produce the source documentation of the EGFR mutation and ALK translocation status in all subjects with non-squamous histology AND for subjects in whom testing is clinically indicated. If either an EGFR sensitizing mutation or ALK translocation is detected, additional information regarding the mutation status of the other molecule is not required. If the clinical site is unable to provide the source documentation, EGFR and ALK testing should be performed per institutional standard of care.
• Subject has measurable disease for response assessment as defined by RECIST v1.1 by the Investigator;
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 (see Appendix 11);
• Subject has a life expectancy of at least 3 months;
• Subject has recovered to Grade ≤1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03 (NCI-CTCAE v4.03) of all clinically significant toxic effects of prior anti-cancer chemotherapy, immunotherapy, radiotherapy or surgery before entering this study, except for alopecia;
• Subject has no major existing comorbidities or medical conditions that would preclude therapy in the opinion of the Investigator;
• Subject has adequate organ function
• A female subject is eligible to participate if she is not pregnant (see Appendix 5), not breastfeeding, and at least one of the following conditions applies:

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;
• Subject has a contraindication to non-steroidal anti-inflammatory drugs (NSAIDs);
• Subject has a known allergy to any component of the study formulation(s);
• Subject has a history of listeriosis;
• Subject has any other serious or uncontrolled physical or mental condition/disease that, as judged by the Investigator, could place the subject at higher risk derived from their participation in the study, could confound results of the study, or would be likely to prevent compliance with the requirements of the study;
• Subject has received chemotherapy and/or radiation therapy (except palliative radiation therapy for disease-related pain) within 2 weeks of the first dose of study treatment;
• Subject has received monoclonal antibody or other biologic therapy within 5 half-lives or 28 days prior to the first dose of study treatment, whichever is shorter. An exception to this exclusion criterion will be pembrolizumab monotherapy for subjects enrolled in Part B;
• Subject has received prior treatment with an Lm-based immunotherapy;
• Subject is receiving or plans to receive future treatment with PI3K or TNFα inhibitors;
• Subject has received a live vaccine within 30 days prior to the first dose of study treatment;
• Subject has not recovered to baseline from AEs, with the exception of alopecia, due to previously administered agent(s);

Where it is running

• City of Hope — Duarte, California, United States
• University of California, Los Angeles — Los Angeles, California, United States
• Emory University — Atlanta, Georgia, United States
• Illinois CancerCare, P.C. — Peoria, Illinois, United States
• The University of Kansas Medical Center — Westwood, Kansas, United States
• Atlantic Health System, Carol G Simon Cancer Center — Morristown, New Jersey, United States
• Montefiore Medical Center — The Bronx, New York, United States
• Providence Cancer Institute — Portland, Oregon, United States
• Virginia Cancer Specialists — Fairfax, Virginia, United States

Full record on ClinicalTrials.gov

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