Study of ADXS11-001 in Participants With High Risk Locally Advanced Cervical Cancer

Phase 3 Study of ADXS11-001 Administered Following Chemoradiation as Adjuvant Treatment for High Risk Locally Advanced Cervical Cancer: AIM2CERV

Locally advanced cervical cancer at higher risk for recurrence (HRLACC) following concurrent chemotherapy and radiation therapy. This is a group of participants with a significant unmet need. The estimated probability of disease recurrence or death within 4 years of diagnosis is 50% and the prognosis is very grave for those who experience a recurrence.

The purpose of the study was to compare the disease free survival (DFS) of ADXS11-001 to placebo administered following cisplatin-based combination chemotherapy and radiation (CCRT) with curative intent in participants with HRLACC.

This was a double-blind, placebo-controlled randomized study of ADXS11-001 administered in the adjuvant setting after completion of CCRT in participants with HRLACC, or death. All eligible participants had received CCRT administered with curative intent according to institutional/national guidelines as well as meeting the minimum standards defined in the protocol. Participants initiated the Screening period within 10 weeks after the completion of CCRT. Baseline radiographic assessments and clinical laboratory assessments were completed no longer than 28 days prior to and 3 days prior to the first study treatment infusion, respectively. Eligible participants were randomized 1:2 to receive either placebo or ADXS11-001. Participants received 1 infusion of study treatment administered every 3 weeks for 3 doses for the first 3 months. Thereafter, participants received study treatment every 8 weeks for a total of 5 doses or until disease recurrence. Participants received a 7-day course of an oral antibiotic or placebo starting 72 hours following the completion of study treatment administration.

Inclusion Criteria:

• Participants must have a biopsy confirmed diagnosis of squamous cell, adenocarcinoma, or adenosquamous carcinoma of the cervix. Histologic confirmation of the original primary tumor is required.
• Participants with HRLACC.
• Participants included those with stage IB2, IIA2, IIB with pelvic lymph node metastases; all FIGO Stage IIIA, IIIB, IVA or any FIGO Stage (except stage IVB) with para-aortic lymph node metastases as defined by the FIGO 2014 staging criteria for carcinoma of the cervix uteri.
• Participants must have received definitive therapy with curative intent, which consist of at least 4 weeks of treatment with cisplatin and a minimum of 40Gy external beam radiation therapy (EBRT).
• Have performance status of 0 or 1 on the gynaecologic Oncology Group (GOG) performance scale
• Demonstrate adequate organ function

Exclusion Criteria:

• Has not achieved disease-free status after completion of CCRT administered with curative intent.
• Has International Federation of Gynecology and Obstetrics (FIGO) Stage IVB
• Has histologies other than squamous cell, adenocarcinoma, or adenosquamous carcinoma of the cervix.
• Has implanted medical device(s) that pose a high risk for colonization and/or cannot be easily removed (e.g., prosthetic joints, artificial heart valves, pacemakers, orthopedic screw(s), metal plate(s), bone graft(s), or other exogenous implant(s)).
• Has a contraindication (sensitivity or allergy) to trimethoprim/sulfamethoxazole and ampicillin.
• Has undergone a previous hysterectomy defined as removal of the entire uterus or will have a hysterectomy as part of their initial cervical cancer therapy. NOTE: Women who have had a partial/subtotal hysterectomy are eligible to participate in the study