A Phase II Trial of Neoadjuvant Treatment With PD-1 Inhibition (Nivolumab) With or Without IDO Inhibition (BMS-986205) and With or Without CTLA-4 Inhibition (Ipilimumab) in Resectable Stage III or IV Melanoma

NCT04007588 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 19-043
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is studying different immunotherapy regimens as a possible treatment for stage III or IV resectable melanoma.

Conditions

Melanoma Stage III; Melanoma Stage IV

Keywords

Melanoma

Outcome Measures

Primary Outcomes (1)

• Major Pathologic Response Rate

  Complete Pathological response rate or near pathological complete response rate on each treatment arm

  2 years

Secondary Outcomes (4)

• Recurrence free survival

  2 years

• Overall Survival Rate

  2 years

• Changes In Infiltrating immune cells From Pre-Treatment To Time Of Excision

  2 Years

• Rates of adverse events and serious adverse events on the different treatment arms.

  2 years

Study Arms (3)

Nivolumab+BMS-986205

EXPERIMENTAL

* Nivolumab will be administered intravenously Day 1 of each 28 day cycle. * BMS-986205 will be administered orally on a daily basis

Drug: Nivolumab; Drug: BMS-986205

Nivolumab

EXPERIMENTAL

-Nivolumab will be administered intravenously Day 1 of each 28 day cycle.

Drug: Nivolumab

Nivolumab+Ipilimumab

EXPERIMENTAL

* Nivolumab will be administered intravenously Day 1 of each 28 day cycle. * Ipilimumab will be administered intravenously every 6 weeks

Drug: Nivolumab; Drug: Ipilimumab

Interventions

Nivolumab DRUG

Nivolumab is a types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack the cancer cells. Nivolumab work by stopping various molecules on cancer cells and body cells from working against the immune system's natural fight against cancer

Also known as: OPDIVO

Nivolumab; Nivolumab+BMS-986205; Nivolumab+Ipilimumab

BMS-986205 DRUG

BMS-986205 is a types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack the cancer cells. BMS-986205 work by stopping various molecules on cancer cells and body cells from working against the immune system's natural fight against cancer

Nivolumab+BMS-986205

Ipilimumab DRUG

Ipilimumab is a types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack the cancer cells. Ipilimumab work by stopping various molecules on cancer cells and body cells from working against the immune system's natural fight against cancer

Also known as: YERVOY

Nivolumab+Ipilimumab

Eligibility Criteria

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

You may qualify if:

• Histologic or cytologic diagnosis of resectable stage III or IV cutaneous melanoma. Patients with melanoma of mucosal origin are not eligible. Patients with acral melanoma that fit criteria are eligible. Patients must have clinically detectable stage III (clinically detectable N1b, N1c, N2b, N2c, N3b or N3c) or stage IV resectable melanoma.
• Age ≥ 18 years.
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
• Participants must have normal organ and marrow function as defined below:
• leukocytes ≥2,000/mcL
• absolute neutrophil count ≥1,500/mcL
• platelets ≥100,000/mcL
• hemoglobin ≥9.0g/dL
• total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
• creatinine within normal institutional limits OR
• creatinine clearance ≥40 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
• C-Reactive Protein \< institutional ULN
• Quantitative or qualitative G6PD assay results must not suggest underlying G6PD deficiency
• Measurable disease (by CT, PET/CT or MRI)

You may not qualify if:

• A history of prior treatment with PD-1 inhibitor, CTLA-4 inhibitor or IDO inhibition. Prior therapy with ipilimumab or Interferon-α-2b in the adjuvant setting is permitted. Participants may not have received live/attenuated vaccines within 30 days of first treatment.
• Participants with uveal or mucosal melanoma
• Participants with known brain metastases must have documented stability for at least 30 days directly prior to study enrollment and not be requiring active treatment for these. Prior radiation, surgery and stereotactic radiosurgery are allowed but must be completed four weeks prior to initiating therapy.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab, ipilimumab, methylene blue or BMS-986205. History or presence of hypersensitivity or idiosyncratic reaction to methylene blue.
• Need for systemic steroids at the time of enrollment. Physiologic replacements at a dose of less than 10 mg daily prednisone equivalent is allowed.
• Blood Methemoglobin \> ULN, assessed in an arterial or venous blood sample or by co-oximetry
• Participants with active ILD/pneumonitis or history of ILD/ pneumonitis requiring steroids.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with nivolumab or BMS-986205, breastfeeding should be discontinued if the mother is treated with nivolumab or BMS-986205. These potential risks may also apply to other agents used in this study.
• Known active HIV, Hepatitis B or Hepatitis C patients. HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for an immunologic effect with the therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
• Autoimmune disease that requires treatment at the time of enrollment. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Participant with a personal or family (ie, in a first-degree relative) history of cytochrome b5 reductase deficiency (previously called methemoglobin reductase deficiency) or other diseases that put them at risk of methemoglobinemia. All participants will be screened for methemoglobin levels prior to randomization.
• Participant with a history of G6PD deficiency or other congenital or autoimmune hemolytic disorders. All participants will be screened for G6PD levels prior to randomization.
• Participants must not have a history of life-threatening toxicity related to prior immune therapy (eg. anti-CTLA-4 or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) except those that are unlikely to re-occur with standard countermeasures (eg. hormone replacement after adrenal crisis).
• Treatment with botanical preparations (eg, herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to randomization.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Bristol-Myers Squibb: collaborator

Study Sites (2)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Nivolumab; linrodostat; Ipilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Elizabeth I Buchbinder, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 1, 2019
• First Posted: July 5, 2019
• Study Start: September 6, 2019
• Primary Completion: December 19, 2019
• Study Completion: December 19, 2019
• Last Updated: February 5, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: BCH - Contact the Technology \& Innovation Development Office at www.childrensinnovations.org or email TIDO@childrens.harvard.edu BIDMC - Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu BWH - Contact the Partners Innovations team at http://www.partners.org/innovation DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu MGH - Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (2)