Window-of-Opportunity Trial of Nivolumab and BMS986205 in Patients With Squamous Cell Carcinoma of the Head and Neck (CA017-087)
Overview
- Phase
- Phase 2
- Status
- Active, not recruiting
- Sponsor
- Thomas Jefferson University
- Enrollment
- 45
- Locations
- 2
- Primary Endpoint
- Objective Response
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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-
- •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.
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.
Arms & Interventions
Arm I (BMS986205, nivolumab)
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.
Intervention: Nivolumab (Biological)
Arm I (BMS986205, nivolumab)
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.
Intervention: IDO1 Inhibitor BMS-986205 (Biological)
Arm I (BMS986205, nivolumab)
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.
Intervention: Therapeutic Conventional Surgery (Procedure)
Arm I (BMS986205, nivolumab)
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.
Intervention: Questionnaire Administration (Other)
Arm II (nivolumab)
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.
Intervention: Nivolumab (Biological)
Arm II (nivolumab)
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.
Intervention: Therapeutic Conventional Surgery (Procedure)
Arm II (nivolumab)
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.
Intervention: Questionnaire Administration (Other)
Outcomes
Primary Outcomes
Objective Response
Time Frame: At 5 weeks
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.
Secondary Outcomes
- Objective pathologic response at time of surgery(At time of surgery)
- 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)
- Multiplex colocalization of resident immune cells(Up to 12 months)
- Kynurenine levels (blood and tumor)(Up to 12 months)
- Intratumoral immune cell populations, immune polarization data, exosome composition, and exosome function in human papilloma virus (HPV) + and HPV- tumors(Up to 12 months)
- Change in immune cell polarization (Th1/Th2; M1/M2) in peripheral blood and tumor specimens(Baseline up to 12 months)
- Localization of immune cells within the tumor(Up to 12 months)
- Incidence of adverse events(Up to 100 days)
- Change in inflammatory markers(Baseline up to 12 months)
- Intratumoral immune cell populations, immune polarization data, exosome composition, and exosome function relative to PD-L1 expression levels(Up to 12 months)