Phase 1-2 Study of ADXS11-001 or MEDI4736 Alone or Combo In Cervical or HPV+ Head & Neck Cancer
Cervical Cancer - Cancer - Head and Neck Cancer
Conditions: official terms
Head and Neck Neoplasms - Uterine Cervical Neoplasms
Study Type
Study Phase
Phase 1/Phase 2
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Name: ADXS11-001 Type: Drug
Name: Medi4736 Type: Drug
Overall Status
Phase 1 (ADXS11-001 + MEDI4736 Combination Therapy) Phase 1 will be a dose-confirmation safety run-in of ADXS11-001 and MEDI4736 combination therapy.

Mandatory fresh biopsies will be obtained pre- and during treatment.

Phase 2:

48 subjects will be randomized 1:1:2 to receive ADXS11-001 monotherapy, MEDI4736 monotherapy or ADXS11 001 + MEDI4736 combination therapy.

Arm A: ADXS11-001 Monotherapy:

Arm B: MEDI4736 Monotherapy:

Arm C: ADXS11-001 + MEDI4736 combination therapy
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

1. Be willing and able to provide written informed consent for the trial

2. Be ≥18 years of age on day of signing informed consent

3. Have histologically or cytologically confirmed, HPV+ recurrent or metastatic SCCHN (oral cavity, oropharynx, hypopharynx, or larynx) or cervix that is not amenable to surgery or standard radiotherapy

4. Have biopsiable disease (should not be a target lesion)

5. Have measurable and/or evaluable disease by RECIST 1.1

6. Have ECOG performance status of 0 or 1

7. Have no major existing co-morbidities or medical conditions that will preclude therapy in the view of the principal investigator.

8. Not be dependent on antibiotics and/or corticosteroids (except for hormone replacement therapy [HRT]).

9. Have adequate organ function defined by the protocol.:

10. Females of childbearing potential who are sexually active with a nonsterilized male partner must use 2 methods of effective contraception from screening and must agree to continue using such precautions for 90 days after the final dose of investigational product; cessation of birth control after this point should be discussed with a responsible physician.

11. Nonsterilized males who are sexually active with a female partner of childbearing potential must use 2 acceptable methods of effective contraception (see Table 2) from Day 1 and for 90 days after receipt of the final dose of investigational product.

Exclusion Criteria:

1. Has received more than 3 prior systemic treatment regimens with chemotherapy, hormonal or mAbs within 4 weeks prior to first dose of study drug or who has not recovered (ie, ≤Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier; has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to study Day 1 or who has not recovered (ie, ≤Grade 1 or at baseline) from adverse events due to a previously administered agent.

2. Has received prior treatment with anti PD-1, anti PDL-1, anti CTLA4 or HPV vaccine treatment.

3. Has any prior Grade ≥3 immune-related adverse event (irAE) while receiving immunotherapy, including anti-CTLA-4 treatment, or any unresolved irAE >Grade 1.

4. Has any pulmonary, ocular, or central nervous system (CNS) toxicity regardless of grade while receiving immunotherapy.

5. Requires additional immunosuppression beyond corticosteroids for resolution of immune-related AEs.

6. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study drug, unless it is an observational (non interventional) clinical study or the follow-up period of an interventional study.

7. Has a diagnosis of immunodeficiency or is receiving any systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to Day 1 of trial treatment.

8. Has any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for invasive malignancy within 2 years. Concurrent use of hormones for non-cancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable.

9. Has known active CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of study drug 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 drug.

10. 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 immune-suppressive agents. Note: Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects who require intermittent use of intranasal, topical, and inhaled corticosteroids or systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent will not be excluded. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.

11. Has evidence of interstitial lung disease or active, non-infectious pneumonitis, active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis)

12. Has an active infection requiring systemic therapy. Prior to dosing with study drug(s), the subject must be at least 5 half lives from their last dose of antibiotic.

13. Has uncontrolled intercurrent illness or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

14. Has a history of psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

15. Has a history of or active primary immunodeficiency or human immunodeficiency virus (HIV) (HIV 1/2 antibodies), active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis), tuberculosis, or history of organ transplant that requires use of immunosuppressives; active hepatitis B (eg, HBsAg reactive) or hepatitis C (eg, HCV RNA [qualitative] is detected), except for subjects with HCC

16. Has unresolved toxicities from prior anticancer therapy, defined as having not resolved to CTCAE v 4.0 Grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria with the exception of alopecia. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by study drug(s) may be included (eg, hearing loss) after consultation with the sponsor medical monitor.

17. Has received a live vaccine within 30 days prior to start of study drug

18. Has a contraindication to administration of penicillin, trimethoprim/sulfa-methoxazole, or ciprofloxacin

19. Has a known allergy to any component of the study drug(s) formulations

20. Females who are pregnant or lactating

21. Has a major surgical procedure (as defined by the investigator) within 30 days prior to the first dose of study drug(s) or still recovering from prior surgery.
UCLA Medical Center
Los Angeles, California, United States
Status: Not yet recruiting
University of California
San Diego, California, United States
Status: Not yet recruiting
Contact: Avi Saini - 858-534-0253 -
Yale New Haven Hospital
New Haven, Connecticut, United States
Status: Not yet recruiting
Contact: Shelby DeCarlo - 203-737-6299 -
University of Miami
Miami, Florida, United States
Status: Recruiting
Contact: Deborah Goodman -
Johns Hopkins University - Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
Status: Not yet recruiting
Mount Sinai Medical Center
New York, New York, United States
Status: Not yet recruiting
Contact: Marshall Posner, MD - 212-659-5609 -
Investigative Clinical Research of Indiana LLC
Canton, Ohio, United States
Status: Recruiting
Contact: Carrie Smith, RN - 330-492-3345 -
University of Oklahoma
Oklahoma City, Oklahoma, United States
Status: Not yet recruiting
Contact: Kimberly Benjamin, RN - 405-271-8778 -
Baylor College of Medicine
Houston, Texas, United States
Status: Not yet recruiting
Start Date
April 2015
Completion Date
December 2019
Advaxis, Inc.
Advaxis, Inc.
Record processing date processed this data on July 28, 2015 page