Nivolumab and BMS986205 in Treating Patients With Stage II-IV Squamous Cell Cancer of the Head and Neck

NCT03854032 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 18P.771JT 13241
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial studies how well nivolumab works, with or without BMS986205, in treating patients with stage II-IV squamous cell cancer of the head and neck. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. BMS986205 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving nivolumab with BMS986205 may work better than nivolumab alone in treating patients with squamous cell cancer of the head and neck.

Conditions

Lip; Oral Cavity Squamous Cell Carcinoma; Pharynx; Larynx; Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response

  Will be assessed by computed tomography (CT) or magnetic resonance imaging (MRI) scans. The proportions of the primary endpoint in the two treatment groups will be compared at 25% significance level using a two-sided test in proportions. Will re-analyze the primary endpoints using a combined patients collection. Historical controls of patients who received nivolumab alone for 4 weeks in previous window of opportunity trial (CA209-9A7) will be included in the control group. Patients' demographic as well as pre-treatment clinical measurements will be compared between the combined control group versus the treatment group to ensure the homogeneity of the two groups. A multi-variable logistic regression model will be used in the statistical analysis, if any difference in the demographic and clinical predictors between treatment groups is detected. Otherwise, the proportions of the primary endpoint in the two treatment groups will be compared at 5% significance level using a two-sided test.

  At 5 weeks

Secondary Outcomes (10)

• Objective pathologic response at time of surgery

  At time of surgery

• Change in immune cell polarization (Th1/Th2; M1/M2) in peripheral blood and tumor specimens

  Baseline up to 12 months

• Change in inflammatory markers

  Baseline up to 12 months

• Change in prevalence of intratumoral immune cell populations (effector T cells [Teff], regulatory T cells [Treg], and tumor-associated macrophages [TAM] in patients treated with Nivolumab and BMS986205 as compared to patients treated with Nivolumab alone

  Baseline up to 12 months

• Localization of immune cells within the tumor

  Up to 12 months

Other Outcomes (5)

• Intratumoral T-cell receptor (TCR) repertoire and diversity

  Up to 12 months

• Change in exosome abundance and composition in the peripheral blood of patients both before and after exposure to both nivolumab and BMS986205 and nivolumab alone

  Baseline up to 12 months

• Rates of wound dehiscence, postop wound infection (requiring antibiotics), and fistula formation

  Up to 12 months

Study Arms (2)

Arm I (BMS986205, nivolumab)

EXPERIMENTAL

Patients receive IDO1 inhibitor BMS-986205 PO QD. Beginning week 2, patients also receive nivolumab IV over 30 minutes on day 1. Treatment repeats for up to 5 weeks in the absence of disease progression or unacceptable toxicity. Patients showing a treatment response receive IDO1 inhibitor BMS-986205 PO QD for 4 additional weeks and receive nivolumab IV over 30 minutes on day 1, then undergo surgery at week 10. Those without a treatment response after 5 weeks undergo surgery within 7 days.

Biological: Nivolumab; Biological: IDO1 Inhibitor BMS-986205; Procedure: Therapeutic Conventional Surgery; Other: Questionnaire Administration

Arm II (nivolumab)

ACTIVE COMPARATOR

Patients receive nivolumab IV over 30 minutes on day 1 in the absence of disease progression or unacceptable toxicity. Patients showing treatment response after 4 weeks receive nivolumab IV over 30 minutes on day 1, then undergo surgery at week 9. Those without a treatment response after 4 weeks undergo surgery within 7 days.

Biological: Nivolumab; Procedure: Therapeutic Conventional Surgery; Other: Questionnaire Administration

Interventions

Nivolumab BIOLOGICAL

Given IV

Also known as: 946414-94-4, BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Arm I (BMS986205, nivolumab); Arm II (nivolumab)

IDO1 Inhibitor BMS-986205 BIOLOGICAL

Given PO

Also known as: (R)-N-(4-chlorophenyl)-2-((1S,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)propenamide, BMS 986205, BMS-986205, BMS986205, IDO-1 Inhibitor BMS-986205, Indoleamine-pyrrole 2,3-Dioxygenase Inhibitor BMS-986205, ONO-7701

Arm I (BMS986205, nivolumab)

Therapeutic Conventional Surgery PROCEDURE

Undergo Surgery

Arm I (BMS986205, nivolumab); Arm II (nivolumab)

Questionnaire Administration OTHER

Ancillary studies

Arm I (BMS986205, nivolumab); Arm II (nivolumab)

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed head and neck squamous cell carcinoma (HNSC).
• Any stage 2 or greater HNSCC (American Joint Committee on Cancer \[AJCC\] 8th edition) of the 1) oral cavity, 2) larynx, 3) hypopharynx, 4) nasal cavity/paranasal sinuses or 5) stage 1 oropharyngeal with lymphadenopathy. Patients with resectable disease that is amenable to surgery are eligible. Patient must have been determined to be candidates for surgical resection by a multi-disciplinary team including a surgeon, a medical oncologist
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• White blood cells 2000/ul or more.
• Absolute neutrophil count 1500/ul or more.
• Platelets 100,000/ul or more.
• Hemoglobin 9 g/dl or more.
• Bilirubin less than or equal to 1.5 x the upper limit of normal (except subjects with Gilbert syndrome, who can have total bilirubin \< 3 mg/dl).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 x the upper limit of normal.
• Glomerular filtration rate (GFR) greater than or equal to 40 ml/min using the Cockcroft-Gault formula or serum creatinine less than or equal to 1.5 x ULN.
• Women of child bearing potential (WOCBP) should have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 21 days of study enrollment.
• WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatment(s) plus 5 months post-treatment completion.
• Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatment(s) plus 7 months post-treatment completion. In addition, male participants must be willing to refrain from sperm donation during this time.
• Males who are sexually active with WOCBP must agree to use a condom during any sexual activity for the duration of treatment with study treatment plus 7 months after the last dose of the study treatment (i.e., 90 days \[duration of sperm turnover\] plus the time required for nivolumab to undergo approximately 5 half-lives). This criterion applies to azoospermic males as well. In addition, male participants must be willing to refrain from sperm donation during this time.
• Male mandatory condom use is regardless of whether the participant has undergone a successful vasectomy or if the female partner is pregnant.

You may not qualify if:

• Patients with nasopharyngeal carcinoma, salivary gland or skin primaries.
• Patients with recurrent head and neck cancer treated previously with chemotherapy, radiation or immunotherapy.
• Any history of a severe hypersensitivity reaction to any monoclonal antibody.
• Any history of allergy to the study drug components.
• Participants with a personal or family (i.e., in a first-degree relative) history or presence of cytochrome b5 reductase deficiency (previously called methemoglobin reductase deficiency) or other diseases that puts them at risk of methemoglobinemia. All participants will be screened for methemoglobin levels prior to randomization.
• Participants with a history of G6PD deficiency or other congenital or autoimmune hemolytic disorders. All participants will be screened for G6PD deficiency prior to randomization.
• Participants with history of serotonin syndrome.
• Participants with active interstitial lung disease (ILD)/pneumonitis or history of ILD/ pneumonitis requiring steroids.
• Prior treatment with BMS-986205 or any other IDO1 inhibitors.
• Quantitative or qualitative G6PD assay results suggesting underlying G6PD deficiency.
• Blood methemoglobin \> upper limit of normal (ULN), assessed in an arterial or venous blood sample or by co-oximetry.
• History or presence of hypersensitivity or idiosyncratic reaction to methylene blue.
• History of allergy or hypersensitivity to any study treatment components, specifically to that of BMS-986205.
• Any concurrent malignancies; exceptions include- basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer or in situ cervical cancer that has undergone potentially curative therapy. Patients with a history of other prior malignancy must have been treated with curative intent and must have remained disease-free for 2 years post-diagnosis.
• Any diagnosis of immunodeficiency or receiving systemic steroid therapy (\> 10 mg daily prednisone equivalents) or any other form of immunosuppressive therapy within 14 days of initiation of therapy.

Sponsors & Collaborators

• Thomas Jefferson University: lead
• Bristol-Myers Squibb: collaborator

Study Sites (2)

Ohio State University

Columbus, Ohio, 43210, United States

Location

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

• Sidney Kimmel Cancer Center
• Thomas Jefferson University Hospital

MeSH Terms

Conditions

Lymphoid Interstitial Pneumonia; Squamous Cell Carcinoma of Head and Neck; Laryngeal Diseases; Carcinoma, Squamous Cell

Interventions

Nivolumab; linrodostat

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

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

Study Officials

• Adam Luginbuhl, MD

  Sidney Kimmel Cancer Center at Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 21, 2019
• First Posted: February 26, 2019
• Study Start: April 9, 2019
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: June 6, 2025

Record last verified: 2025-06

Locations

US (2)