LipPhase 2NCT03854032
Nivolumab and BMS986205 in Treating Patients With Stage II-IV Squamous Cell Cancer of the Head and Neck
A Phase 2 study testing Nivolumab, IDO1 Inhibitor BMS-986205 and Therapeutic Conventional Surgery in people with Lip and Oral Cavity Squamous Cell Carcinoma, run by Thomas Jefferson University at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lip, Oral Cavity Squamous Cell Carcinoma, Pharynx
- What is being tested?
- Nivolumab, IDO1 Inhibitor BMS-986205 and Therapeutic Conventional Surgery
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 2 sitesUnited States
- Study dates
- 9 Apr 2019to 14 Mar 2023
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Ohio State University
Columbus, Ohio, 43210
Sidney Kimmel Cancer Center at Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
About this study
Official title: Window-of-opportunity Trial of Nivolumab and BMS-986205 in Patients With Squamous Cell Carcinoma of the Head and Neck (HNSCC)
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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:
- 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.
- Being tested
- Nivolumab, IDO1 Inhibitor BMS-986205, Therapeutic Conventional Surgery, Questionnaire Administration
- Medical subject headings
- Lymphoid Interstitial Pneumonia, Squamous Cell Carcinoma of Head and Neck, Laryngeal Diseases, Carcinoma, Squamous Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabBiological
Also called 946414-94-4, BMS-936558, MDX-1106, NIVO
Given IV
IDO1 Inhibitor BMS-986205Biological
Also called (R)-N-(4-chlorophenyl)-2-((1S,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)propenamide, BMS 986205, BMS-986205, BMS986205
Given PO
Therapeutic Conventional SurgeryProcedure or surgery
Undergo Surgery
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Arm A: 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. 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. Receives: Biological: Nivolumab; Biological: IDO1 Inhibitor BMS-986205; Procedure: Therapeutic Conventional Surgery; Other: Questionnaire Administration |
| Arm B: Group I - Nivolumab Only | Experimental | 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. Receives: Biological: Nivolumab; Procedure: Therapeutic Conventional Surgery; Other: Questionnaire Administration |
| Arm C: Group II - Nivolumab Only | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response
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.
Measured: At 5 weeks
Secondary outcomes (10)
Objective Pathologic Response at Time of Surgery
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).
Measured: At time of surgery
Change in Immune Cell Polarization (Th1/Th2; M1/M2) in Peripheral Blood and Tumor Specimens
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%.
Measured: Baseline up to 12 months
Change in Inflammatory Markers
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%
Measured: 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
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%.
Measured: Baseline up to 12 months
Localization of Immune Cells Within the Tumor
Will be analyzed using confocal microscopy.
Measured: Up to 12 months
Multiplex Colocalization of Resident Immune Cells
Will utilize 5-6 markers per section.
Measured: Up to 12 months
Ratio of Tryptophan to Kynurenine
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
Measured: Up to 12 months
Intratumoral Immune Cell Populations, Immune Polarization Data, Exosome Composition, and Exosome Function in Human Papilloma Virus (HPV) + and HPV- Tumors
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%.
Measured: Up to 12 months
Intratumoral Immune Cell Populations, Immune Polarization Data, Exosome Composition, and Exosome Function Relative to PD-L1 Expression Levels
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%.
Measured: Up to 12 months
Number of Immune Related Adverse Events
Number of immune related adverse events. Adverse Events will be graded by Common Terminology Criteria for Adverse Events version 5.0.
Measured: Up to 100 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2019
- Study start9 Apr 2019
- Primary completion10 Feb 2022
- Study completion14 Mar 2023
Why it stopped: Study was terminated early due to toxicity concerns by the Sponsor.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LipStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- Thomas Jefferson University
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Adam Luginbuhl, MD, Principal investigator, Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03854032
- Sponsor's protocol ID
- 18P.771
- Other IDs
- JT 13241
- Status last verified
- Sep 2026
- First submitted
- 21 Feb 2019
- Last updated
- 19 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No