A Phase 2 Study of Axalimogene Filolisbac (ADXS11-001) in Participants With Carcinoma of the Anorectal Canal

Inclusion criteria

• Must have cancer of the anal canal OR rectal cancer.
• Must have metastatic disease or persistent/recurrent loco-regional disease
• Prior Therapy: may have received <2 regimens for disease in the metastatic setting. At least one line of therapy.
• Be willing and able to provide written informed consent for the trial.
• Be ≥18 years of age on day of signing informed consent.
• Have measurable disease based on response evaluation criteria in solid tumors (RECIST) 1.1
• Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Demonstrate adequate organ function as defined in protocol.
• Females cannot be pregnant or breastfeeding and must take two methods of birth control

Exclusion criteria

• Has not recovered (for example, Grade ≤1 or at baseline) from adverse events (AEs), with the exception of alopecia or Grade ≤2 neuropathy, due to a previously administered agent
• Has a diagnosis of immunodeficiency
• Has known additional malignancy that is progressing or requires active treatment. Treatment of an additional malignancy with chemotherapy, immunotherapy, biologic or hormonal therapy must have occurred 2 years prior. Concurrent use of hormones for non-cancer-related conditions (for example, insulin for diabetes and hormone replacement therapy) is acceptable

• Note: Local treatment of isolated lesions for palliative intent (for example, by local surgery or radiotherapy), basal cell carcinoma of the skin, or squamous cell carcinoma of the skin, or ductal carcinoma in situ of the breast that has/have been surgically cured is acceptable
• Has known active central nervous system metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided the metastases are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of study 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 the first dose of study treatment
• Has concurrent unstable or uncontrolled medical condition (example, active uncontrolled systemic infection, poorly controlled hypertension or history of poor compliance with an anti-hypertensive regimen, unstable angina, congestive heart failure, uncontrolled diabetes) or other chronic disease, which in the opinion of the investigator, could compromise the patient or the study
• Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents

• Participants with vitiligo or resolved childhood asthma/atopy would be an exception to this rule.
• Participants that require intermittent use of inhaled steroids, bronchodilators or local steroid injections may be allowed with sponsor approval.
• Participants with hypothyroidism stable on hormone replacement or Sjorgen's Syndrome will not be excluded from the study
• Has an active infection requiring systemic therapy. Prior to dosing with study treatment(s), the subject must be at least 5 half-lives from their last dose of antibiotic
• Has any other serious or uncontrolled physical or mental condition/disease that, as judged by the investigator, could place the patient at higher risk derived from his/her participation in the study, could confound results of the study, or would be likely to prevent the patient from complying with the requirements of the study or completing the study.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Participant has implanted medical device(s) that pose a high risk for colonization and/or cannot be easily removed (examples, prosthetic joints, artificial heart valves, pacemakers, orthopedic screw[s], metal plate[s], bone graft[s], or other exogenous implant[s]).

• Note: More common devices and prosthetics which include arterial and venous stents, dental and breast implants and venous access devices (example, Port-a-Cath or Mediport) are permitted. Participants with any other devices or implants must be approved by Sponsor prior to participation
• Any participant currently requiring or anticipated to require tumor necrosis factor (TNF) blocking agent (example: infliximab) therapy for diagnosis of rheumatologic disease or inflammatory bowel disease (e.g., ankylosing spondylitis, Crohn disease, plaque psoriasis, psoriatic arthritis, rheumatoid arthritis or ulcerative colitis
• Participants who are currently receiving or who have received any phosphoinositide 3-kinase (PI3K) inhibitor within 30 days prior to registration
• Participant has a contraindication (example: sensitivity/allergy) to trimethoprim/sulfamethoxazole and ampicillin
• Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
• Has known active hepatitis B or hepatitis C
• Has a known allergy to any component of the study treatment(s) formulations
• Has contraindication to administration of non-steroidal anti-inflammatory drugs (NSAIDs)
• Has undergone a major surgery, including surgery for a new artificial implant and/or medical device which is permitted by the protocol, within 6 weeks prior to the initiation of ADXS11-001 treatment

• Note: If the participant had a major surgery, all toxicities and/or complications from the intervention must have recovered to at least the baseline or Grade 1 prior to the initiation of ADXS11-001 study therapy. Consult with the Sponsor prior to enrolling participants on the study who recently had a major surgery or have a new artificial implant and/or medical device
• In the opinion of the investigator has rapidly progressing disease, OR has life expectancy of <6 months, OR would be unable to receive at least 1 cycle of therapy