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

Study Overview
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Brief Summary
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This is a single arm Phase 2 study. Stage 1 and 2 of the study are monotherapy evaluations of ADXS11-001 in 31 and 24 participants, respectively with persistent/recurrent, loco-regional or metastatic squamous cell carcinoma (SCCA) of the anorectal canal that have received at least 1 regimen for the treatment of advanced disease.

Official Title
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Phase 2 Study of ADXS11-001 in Subjects With Persistent/Recurrent, Loco-Regional or Metastatic Squamous Cell Carcinoma of the Anorectal Canal

Conditions
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Anal Cancer, Rectal Cancer

Intervention / Treatment
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* Drug: Axalimogene filolisbac


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Axalimogene filolisbac<br>Participants received intravenous (IV) infusion of axalimogene filolisbac administered over 60 minutes every 3 weeks at a dose of 1 x 10^9 colony forming units (cfu) for up to 2 years or until a discontinuation criterion was met (documented progression, unacceptable adverse events, withdrawn due to investigator's discretion, participant withdraws consent, pregnancy or noncompliance with study procedures or treatments). A treatment cycle was defined as 9 weeks in duration. | Drug: Axalimogene filolisbac<br> <br> * Other names: ADXS11-001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | Best response was defined as achievement of complete response (CR) or partial response (PR) per RECIST 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeters (mm). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | From the first dose until progression or death (maximum duration: 68 weeks) | 
| Progression Free Survival | Progression free survival was defined as the time from treatment start until disease progression or death whichever occurred earlier. Participants who have not progressed or who are still alive at the time of evaluation will be censored for the analysis. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. Kaplan-Meier method was used for estimating progression free survival. | From the first dose until progression or death (maximum duration: 68 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | An adverse event was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, was also an adverse event. | From the first dose until end of study (maximum duration: 72 weeks) |