Nivolumab and HPV-16 Vaccination in Patients With HPV-16 Positive Incurable Solid Tumors

NCT02426892 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2014-1047NCI-2015-01004
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if nivolumab combined with ISA101 can help to control cancer that has spread. The safety of the study drugs will also be studied. This is an investigational study. ISA101 is not FDA approved or commercially available. It is currently being used for research purposes only. Nivolumab is FDA approved to treat certain types of melanoma in patients who no longer respond to other drugs. Combining ISA101 with nivolumab is investigational. The study doctor can explain how the study drugs are designed to work. Up to 28 participants will be enrolled in this study. All will take part at MD Anderson.

Conditions

Solid Tumors

Keywords

Solid Tumors; HPV-16 Positive Incurable Solid Tumors; ISA101; HPV-16 vaccination; Nivolumab; BMS-936558; Opdivo

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Overall Response Rate (ORR)

  ORR defined as sum of subjects with a complete response (CR) and partial response (PR) divided by number of evaluable subjects at 11 weeks from start of treatment. RECIST 1.1 criteria used for assessment. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  From the time of the first protocol-specific intervention, every 6 weeks until progression, death, withdrawal of consent or study completion, an average of 4.5 years

Secondary Outcomes (5)

• Median Progression Free Survival (PFS)

  From the time of the first protocol-specific intervention, every 6 weeks until progression, death, withdrawal of consent or study completion, an average of 4.5 years.

• Progression Free Survival (PFS) Rates at 2 and 3 Years

  From the time of the first protocol-specific intervention, every 6 weeks until progression, death, withdrawal of consent or study completion, an average of 3 years.

• Median Overall Survival

  3 years

• Overall Survival (OS) Rates at 2 and 3 Years

  up to 3 years

• Number of Participants With Adverse Events

  at baseline, and continuously throughout the study at the beginning of each subsequent cycle, up to 3 years

Study Arms (1)

ISA101 + Nivolumab

EXPERIMENTAL

HPV-16 vaccination (ISA 101) administered subcutaneously at 100 mcg for a total of 3 doses at 3 to 4 weeks intervals starting on Day 1. Nivolumab administered intravenously at 3 mg/kg every 2 weeks beginning on day 8 after the first vaccine dose. There are 3 weeks in Cycle 1 and 2 weeks in Cycles 2 and beyond.

Biological: ISA 101; Drug: Nivolumab

Interventions

ISA 101 BIOLOGICAL

100 mcg administered subcutaneously for a total of 3 doses at 3 to 4 weeks intervals starting on Day 1.

ISA101 + Nivolumab

Nivolumab DRUG

3 mg/kg administered by vein every 2 weeks beginning on Day 8 after the first vaccine dose.

Also known as: BMS-936558, Opdivo

ISA101 + Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Written Informed Consent: a. Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care. b) Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study.
• Target Population: a. Men and women \>/= 18 years of age. b. Eastern Cooperative Oncology Group (ECOG) performance status of \</= 1. c. Subjects with histologically- or cytologically-documented incurable Human Papillomavirus (HPV)-16 positive solid tumors including oropharyngeal squamous cell carcinoma (OPSCC), cervical, vulvar, vaginal, anal, penile cancer. Incurable HPV-16 solid tumors are defined as tumors which are not curable by salvage approaches including resection and/or re-irradiation. HPV-16 serotype will be assessed by Cervista assay.
• Target Population: Subjects can be treatment naïve for metastatic or incurable locally advanced HPV-16 positive solid tumors or can have one prior line of treatment.Patients are eligible upon progression after definitive local treatment (usually concurrent chemoradiation) if they are not candidates for salvage surgery or re-irradiation. Patients are also eligible after progression on first line chemotherapy for recurrent disease.
• Target Population: h. All baseline laboratory requirements will be assessed and should be obtained within -14 days of study registration. Screening laboratory values must meet the following criteria: i) WBCs \>/= 2000/uL; ii) Neutrophils \>/= 1500/uL; iii) Platelets \>/= 100 x 10\^3/uL; iv) Hemoglobin \>/= 9.0 g/dL; v) Serum creatinine of \</= 1.5 X ULN or creatinine clearance \> 40 mL/minute (using Cockcroft/Gault formula). Female CrCl= (140- age in years) x weight in kg x 0.85 72 x serum creatinine in mg/ dL. Male CrCl= (140- age in years) x weight in kg x 1.00 72 x serum creatinine in mg/ dL; vi) AST \</= 1.5X ULN; vii) ALT \</= 1.5X ULN; viii) Total bilirubin \</= ULN (except subjects with Gilbert Syndrome who must have total bilirubin \<3.0 mg/dl).
• Age and Reproductive Status: a) Women of childbearing potential (WOCBP) must use method(s) of contraception for 30 days + 5 half-lives (60 days) of the study drugs. For a teratogenic study drug and/or when there is insufficient information to assess teratogenicity (preclinical studies have not been done), a highly effective method(s) of contraception (failure rate of less than 1% per year) is required. Highly effective birth control in this study is defined as a double barrier method. Examples include a condom (with spermicide) in combination with a diaphragm, cervical cap, or intrauterine device (IUD). The individual methods of contraception should be determined in consultation with the investigator. b) WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of investigational product.
• Age and Reproductive Status: c) Women must not be breastfeeding. d) Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. The investigator shall review contraception methods and the time period that contraception must be followed. Men that are sexually active with WOCBP must follow instructions for birth control for a period of 90 days plus the time required for the investigational drug to undergo 5 half-lives (60 days).

You may not qualify if:

• Target Disease Exceptions: a. Subjects with active CNS metastases are excluded. Subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of \</= 10 mg daily prednisone (or equivalent) for 2 weeks. b. Subjects with carcinomatous meningitis.
• Medical History and Concurrent Diseases: a. Subjects with active, known or suspected systemic autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. b. Subjects with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start. Inhaled or topical steroids, and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
• Medical History and Concurrent Diseases: c. Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). d. Subjects with a history of interstitial lung disease. e. Other active malignancy requiring concurrent intervention. f. Subjects with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period.
• Medical History and Concurrent Diseases: g. Subjects with toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue that have not resolved to grade 1 (NCI CTCAE version 4) or baseline before administration of study drug. h. Subjects who have not recovered from the effects of major surgery or significant traumatic injury at least 14 days before the first dose of study treatment. i. Treatment with any investigational agent within 28 days of first administration of study treatment.
• Physical and Laboratory Test Findings: a) Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). b) Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection.
• Allergies and Adverse Drug Reaction: a) History of severe hypersensitivity reactions to other monoclonal antibodies. b) History of allergy or intolerance (unacceptable adverse event) to study drugs components.
• Sex and Reproductive Status: a) WOCBP who are pregnant or breastfeeding. b) Women with a positive pregnancy test at enrollment or prior to administration of study medication

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• ISA Pharmaceuticals B.V.: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Sousa LG, Rajapakshe K, Rodriguez Canales J, Chin RL, Feng L, Wang Q, Barrese TZ, Massarelli E, William W, Johnson FM, Ferrarotto R, Wistuba I, Coarfa C, Lee J, Wang J, Melief CJM, Curran MA, Glisson BS. ISA101 and nivolumab for HPV-16+ cancer: updated clinical efficacy and immune correlates of response. J Immunother Cancer. 2022 Feb;10(2):e004232. doi: 10.1136/jitc-2021-004232.

  PMID: 35193933 DERIVED

• Massarelli E, William W, Johnson F, Kies M, Ferrarotto R, Guo M, Feng L, Lee JJ, Tran H, Kim YU, Haymaker C, Bernatchez C, Curran M, Zecchini Barrese T, Rodriguez Canales J, Wistuba I, Li L, Wang J, van der Burg SH, Melief CJ, Glisson B. Combining Immune Checkpoint Blockade and Tumor-Specific Vaccine for Patients With Incurable Human Papillomavirus 16-Related Cancer: A Phase 2 Clinical Trial. JAMA Oncol. 2019 Jan 1;5(1):67-73. doi: 10.1001/jamaoncol.2018.4051.

  PMID: 30267032 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Interventions

Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Renata Ferrarotto,MD, Associate Professor, Thoracic-Head & Neck Med Onc
• Organization: UT MD Anderson Cancer Center

rferrarotto@mdanderson.org

(713) 745-6774

Study Officials

• Bonnie S. Glisson, MD, BS

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2015
• First Posted: April 27, 2015
• Study Start: December 23, 2015
• Primary Completion: November 30, 2021
• Study Completion: November 30, 2021
• Last Updated: April 18, 2023
• Results First Posted: April 18, 2023

Record last verified: 2022-12

Locations

US (1)