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

Objectives

To evaluate the safety and tolerability of ADXS-503, administered as monotherapy in Part A
and in combination with pembrolizumab in Part B, and to determine the maximum tolerated dose
(MTD) or maximum administered dose (MAD). As well, to characterize the preliminary anti-tumor
activity of ADXS-503, administered in combination with pembrolizumab in Part C, per RECIST
v1.1.

Eligibility

1. 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;
2. Subject is =18 years of age upon signing the Informed Consent Form;
3. Subject has histologically or cytologically confirmed stage IV (metastatic) squamous or non-squamous NSCLC
4. 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.
5. Subjects will be eligible for Part A irrespective of PD-L1 expression.
6. 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.
7. Part B only:
8. Subject is undergoing treatment with pembrolizumab monotherapy for metastatic NSCLC
9. Subject's most recent tumor assessment is consistent with PD according to RECIST v1.1
10. The Investigator has determined that PD should be confirmed within 4-8 weeks, and pembrolizumab treatment will continue pending PD confirmation
11. Subject is willing to undergo a confirmatory scan 4-8 weeks from the prior scan that indicated progression on pembrolizumab
12. 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.
13. Part C only:
14. 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.
15. 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.
16. Subject's tumor has PD-L1 expression of =50%, as determined by immunohistochemistry (IHC) at a central laboratory.
17. 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.
18. Subject has measurable disease for response assessment as defined by RECIST v1.1 by the Investigator;
19. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 (see Appendix 11);
20. Subject has a life expectancy of at least 3 months;
21. 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;
22. Subject has no major existing comorbidities or medical conditions that would preclude therapy in the opinion of the Investigator;
23. Subject has adequate organ function
24. 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:
25. Not a woman of childbearing potential (WOCBP) as defined in Appendix 5 OR
26. A WOCBP who agrees to follow the contraceptive guidance in Appendix 5 during the treatment period and for at least 120 days after the final dose of study treatment;
27. A female subject of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study treatment and throughout the study as defined in the SoA. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
28. A male subject is eligible if he agrees to follow the contraceptive guidance in Appendix 5 during the treatment period and for at least 120 days after the final dose of study treatment.

Treatment Sites in Georgia