NCT03854032 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: TERMINATED
Registry last update: 2026-10-19

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Objective Response

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outcome · POSTED

Objective Pathologic Response at Time of Surgery

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outcome · POSTED

Change in Immune Cell Polarization (Th1/Th2; M1/M2) in Peripheral Blood and Tumor Specimens

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outcome · POSTED

Change in Inflammatory Markers

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outcome · POSTED

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

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outcome · POSTED

Localization of Immune Cells Within the Tumor

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outcome · POSTED

Multiplex Colocalization of Resident Immune Cells

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outcome · POSTED

Ratio of Tryptophan to Kynurenine

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outcome · POSTED

Intratumoral Immune Cell Populations, Immune Polarization Data, Exosome Composition, and Exosome Function in Human Papilloma Virus (HPV) + and HPV- Tumors

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outcome · POSTED

Intratumoral Immune Cell Populations, Immune Polarization Data, Exosome Composition, and Exosome Function Relative to PD-L1 Expression Levels

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outcome · POSTED

Number of Immune Related Adverse Events

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outcome · POSTED

Intratumoral T-cell Receptor (TCR) Repertoire and Diversity

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outcome · POSTED

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

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outcome · POSTED

Number of Participants With Wound Dehiscence

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outcome · POSTED

Changes in Tumor Volume and Rates of Radiographic Response

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outcome · POSTED

Patient-reported Outcomes

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * 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. * Investigators shall counsel WOCBP, and male participants who are sexually active with WOCBP, on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise on the use of highly effective methods of contraception, which have a failure rate of \< 1% when used consistently and correctly. Hormonal contraceptives are prohibited methods of contraception for participants receiving BMS-986205 this study who are WOCBP. * All subjects must be able to comprehend and sign a written informed consent document. Exclusion Criteria: * 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. * Patients that have 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 (\> 10 mg daily prednisone equivalents) or immunosuppressive agents. Subjects with vitiligo, type I diabetes mellitus, or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study. * Patients must not be receiving any other investigational agents. * Patients with uncontrolled intercurrent illnesses including, but not limited to an active infection requiring systemic therapy or a known psychiatric or substance abuse disorder(s) that would interfere with cooperation with the requirements of the trial. * Patients must not be pregnant or breastfeeding. * Patients with a known human immunodeficiency virus infection (HIV 1/2 antibodies) or acquired immunodeficiency syndrome (HIV/AIDS), active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected). * Patients with any evidence of current interstitial lung disease (ILD) or pneumonitis. * Patients with prior history of ILD or non-infectious pneumonitis that required steroids. * Patients who have received a live vaccine within 30 days of the planned start of study therapy.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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. Nivolumab is administered as a 480mg intravenous (IV) infusion once every 4 weeks. BMS986205 is administered orally at a dose of 100 mg once daily.
intervention Names
Biological: Nivolumab
Biological: IDO1 Inhibitor BMS-986205
Procedure: Therapeutic Conventional Surgery
Other: Questionnaire Administration
label
Arm A: BMS986205 + Nivolumab
type
EXPERIMENTAL
description
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. Nivolumab is administered as a 480mg intravenous (IV) infusion once every 4 weeks.
intervention Names
Biological: Nivolumab
Procedure: Therapeutic Conventional Surgery
Other: Questionnaire Administration
label
Arm B: Group I - Nivolumab Only
type
EXPERIMENTAL
description
Data from Contemporaneous Study 10237 (NCT03238365) participants who received Nivolumab alone prior to surgery is used as a historical controls under the current window of treatment (WOT), to bolster the control group. Nivolumab was administered as a 240mg intravenous (IV) infusion every 2 weeks for 2 doses over a 4-week treatment period prior to surgical resection.
label
Arm C: Group II - Nivolumab Only
type
NO_INTERVENTION

interventions

arm Group Labels
Arm A: BMS986205 + Nivolumab
Arm B: Group I - Nivolumab Only
description
Given IV
name
Nivolumab
other Names
946414-94-4
BMS-936558
MDX-1106
NIVO
ONO-4538
Opdivo
type
BIOLOGICAL
arm Group Labels
Arm A: BMS986205 + Nivolumab
description
Given PO
name
IDO1 Inhibitor BMS-986205
other Names
(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
type
BIOLOGICAL
arm Group Labels
Arm A: BMS986205 + Nivolumab
Arm B: Group I - Nivolumab Only
description
Undergo Surgery
name
Therapeutic Conventional Surgery
type
PROCEDURE
arm Group Labels
Arm A: BMS986205 + Nivolumab
Arm B: Group I - Nivolumab Only
description
Ancillary studies
name
Questionnaire Administration
type
OTHER

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 65
type: ACTUAL

Registered outcome plans (not posted results)

other Outcomes

description
Assesses with next generation sequencing.
measure
Intratumoral T-cell Receptor (TCR) Repertoire and Diversity
time Frame
Up to 12 months
description
Will be compared between treatment arms using two-sample t-tests.
measure
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
time Frame
Baseline up to 12 months
description
Number of Participants with wound dehiscence, postop wound infection (requiring antibiotics), and fistula formation
measure
Number of Participants With Wound Dehiscence
time Frame
Up to 12 months
description
Will be summarized by treatment arm and compared using two-sample t-tests or Fisher's exact test, as appropriate.
measure
Changes in Tumor Volume and Rates of Radiographic Response
time Frame
Baseline up to 12 months
description
Data will be collected and correlated to both immune cell composition and polarization and tumor radiographic response using scores from Patient Health Questionnaire (PHQ)2/9, Functional Assessment of Cancer Therapy- General (FACT-G), and FACT-head and neck (HN). Will conduct descriptive statistics and will summarize variable of interest using standard statistics such as frequency tables, means, and standard deviations. All measures will be evaluated for reliability and factor analyses will be conducted.
measure
Patient-reported Outcomes
time Frame
Up to 12 months

primary Outcomes

description
Radiographic response was assessed at the primary site and involved lymph nodes. Participants with ≥10% volumetric reduction at either site and no progression received a second treatment cycle before surgery, while those with stable disease or progression proceeded to surgery at the 5-week evaluation. The study hypothesized that adding an IDO inhibitor to PD-1 blockade would improve radiographic response. The primary endpoint was the proportion of participants eligible for a second cycle. The 10% cutoff was based on prior publications showing that volumetric analysis is more sensitive than single-axis RECIST v1.1 and allows minor immune-related increases (0-9%) while defining \>10% growth as progression.
measure
Objective Response
time Frame
At 5 weeks

secondary Outcomes

description
Pathologic specimens were independently graded by two pathologists as outlined in our previous publication (2). The entire mass or surgical specimen (in the event of a partial/ complete response) was sectioned to calculate the pTR. Criteria for response included evidence of macrophage reaction, multinucleated giant cells and granulomas, fibrosis adjacent to residual tumor nests. In complete responders where no more viable tumor was identified, alteration of the normal tissue architecture by fibrosis and macrophage reaction was used to identify areas of previously viable malignancy. Tumors with pTR of ≥20% were defined as responders (R), while those with pTR \<20% were defined as minimal or non-responders (NR) at the primary site and Lymph Nodes (LNs).
measure
Objective Pathologic Response at Time of Surgery
time Frame
At time of surgery
description
Will be analyzed and compared using multiplex cytokine analysis collected before and after exposure to nivolumab +/- IDO1 inhibitor BMS-986205 (BMS986205). If there is at least one significant difference between groups among the primary outcomes, the two randomization arms will be compared with respect to each secondary outcome using two-sample t-tests. P-values for comparisons of changes in secondary outcomes will be adjusted using the method of Benjamini and Hochberg to control the FDR among the secondary outcomes at 5%.
measure
Change in Immune Cell Polarization (Th1/Th2; M1/M2) in Peripheral Blood and Tumor Specimens
time Frame
Baseline up to 12 months
description
These include soluble (s)CD40 ligand (L), EGF, eotaxin, FGF-2, Flt-3 ligand, fractalkine, granulocyte colony-stimulating factor (G-CSF), granulocyte colony-macrophage (GM)-CSF, GRO, IFN-alpha2, IL-1alpha, IL-1beta, IL-1ra, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-12 (p40), IL-13, IL-15, IL-17A, IP-10, MCP-1, MCP-3, MDC (CCL22), MIP-1alpha, MIP-1beta, PDGF-AA, PDGF-AB/BB, RANTES, TGF-alpha, TNF-alpha, VEGF. If there is at least one significant difference between groups among the primary outcomes, the two randomization arms will be compared with respect to each secondary outcome using two-sample t-tests. P-values for comparisons of changes in secondary outcomes will be adjusted using the method of Benjamini and Hochberg to control the FDR among the secondary outcomes at 5%
measure
Change in Inflammatory Markers
time Frame
Baseline up to 12 months
description
Assessed by immunohistochemistry (IHC). If there is at least one significant difference between groups among the primary outcomes, the two randomization arms will be compared with respect to each secondary outcome using two-sample t-tests. P-values for comparisons of changes in secondary outcomes will be adjusted using the method of Benjamini and Hochberg to control the FDR among the secondary outcomes at 5%.
measure
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
time Frame
Baseline up to 12 months
description
Will be analyzed using confocal microscopy.
measure
Localization of Immune Cells Within the Tumor
time Frame
Up to 12 months
description
Will utilize 5-6 markers per section.
measure
Multiplex Colocalization of Resident Immune Cells
time Frame
Up to 12 months
description
Tryptophan and kynurenine concentrations were measured in plasma samples using validated assays. The outcome is expressed as the ratio of tryptophan to kynurenine, a marker of IDO1 activity. Results are reported as median values with full range (minimum to maximum) across participants
measure
Ratio of Tryptophan to Kynurenine
time Frame
Up to 12 months
description
Baseline IHC staining for P16 will be performed as a surrogate for HPV status. If there is at least one significant difference between groups among the primary outcomes, the two randomization arms will be compared with respect to each secondary outcome using two-sample t-tests. P-values for comparisons of changes in secondary outcomes will be adjusted using the method of Benjamini and Hochberg to control the FDR among the secondary outcomes at 5%.
measure
Intratumoral Immune Cell Populations, Immune Polarization Data, Exosome Composition, and Exosome Function in Human Papilloma Virus (HPV) + and HPV- Tumors
time Frame
Up to 12 months
description
Assessed by IHC. If there is at least one significant difference between groups among the primary outcomes, the two randomization arms will be compared with respect to each secondary outcome using two-sample t-tests. P-values for comparisons of changes in secondary outcomes will be adjusted using the method of Benjamini and Hochberg to control the FDR among the secondary outcomes at 5%.
measure
Intratumoral Immune Cell Populations, Immune Polarization Data, Exosome Composition, and Exosome Function Relative to PD-L1 Expression Levels
time Frame
Up to 12 months
description
Number of immune related adverse events. Adverse Events will be graded by Common Terminology Criteria for Adverse Events version 5.0.
measure
Number of Immune Related Adverse Events
time Frame
Up to 100 days

Full study description

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.
detailed Description: PRIMARY OBJECTIVES: I. To assess the impact of IDO1 inhibitor BMS-986205 (BMS986205) and nivolumab versus nivolumab alone on tumor radiographic response both at the primary tumor site and in regional lymph nodes by investigator assessment at 5 weeks. SECONDARY OBJECTIVES: I. To investigate whether adding the IDO1 - inhibitor, BMS986205, to nivolumab therapy affects intratumoral and systemic anti-tumor immunity. II. To assess the impact of BMS986205 and nivolumab verses nivolumab alone on pathologic treatment effect bother at the primary and regional lymph nodes. III. To determine the effect of BMS986205 and nivolumab versus nivolumab alone on immune cell composition within the tumor microenvironment including the presence of effector T cells (Teff), regulatory T cells (Treg), and tumor-associated macrophages (TAM). IV. To further characterize the effect of BMS986205 when combined with nivolumab on kynurenine production and correlate these levels with effects on immune cell composition and polarization. V. To review the relationship of p16 status by immunohistochemistry with immune cell polarization, tumor radiographic response, and immune cell composition. VI. To review the relationship of PD-L1 status by immunohistochemistry with immune cell polarization, tumor radiographic response, and immune cell composition. VII. To assess the safety and tolerability of BMS986205 and nivolumab. VIII. Evaluate surgical wound healing post treatment. EXPLORATORY OBJECTIVES: I. To further characterize the effect of BMS986205 and nivolumab versus nivolumab alone through analysis of T cell repertoire. II. To assess the interactions between the immune and metabolic microenvironment through analysis of alterations in exosome composition in peripheral blood as it related to immune, cytokine and metabolic alterations before, during and after treatment. III. To identify risks for poor physical and mental health outcomes; examine bio-behavioral factors associated with cancer treatment outcomes; and evaluate the physical and psychosocial needs of cancer survivors through patient reported outcomes. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive IDO1 inhibitor BMS-986205 orally (PO) once daily (QD). Beginning week 2, patients also receive nivolumab intravenously (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. ARM II: 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. After completion of study treatment, patients are followed up periodically for 12 months.

Source references