Multiple Class I Peptides & Montanide ISA 51 VG w Escalating Doses of Anti-PD-1 ab BMS936558

NCT01176461 | Completed Phase 1

• 4 other identifiers: MCC-15400NCI-P-7997CA209-006/00710-15526-99-01
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot phase 1, open-label, single center, multi-dose, dose-escalation study of BMS-936558 in combination with or without a peptide vaccine. The purpose of this study is to test the side effects of an investigational vaccine with an immune booster. Investigators also wish to find out its effects on the patient's immune system and whether it will shrink their melanoma.

Conditions

Melanoma (Skin)

Keywords

recurrent melanoma; stage IIIA melanoma; stage IIIB melanoma; stage IIIC melanoma; stage IV melanoma

Outcome Measures

Primary Outcomes (1)

• Best Overall Response Rate (BORR)

  The primary analysis is the BORR as determined using irRC. The BORR will be summarized using descriptive statistics.

  2 years, 6 months

Secondary Outcomes (2)

• Time to Response

  2 years, 6 months

• Duration of Response

  2 years, 6 months

Study Arms (2)

A1 - Phase I Dose Escalation

EXPERIMENTAL

Cohorts 1 through 5. Each treatment cycle is comprised of 6 doses of BMS-936558 and 6 peptide vaccines administered every 2 weeks for 12 weeks (cohort 6 has no peptides) (Cycle 1: Weeks 1, 3, 5, 7, 9, and 11; Cycle 2: Weeks 13, 15, 17, 19, 21, and 23) with tumor response assessments at the end of each cycle (during Weeks 12 and 24).

Biological: MART-1; Biological: NY-ESO-1; Biological: gp100:209-217(210M); Biological: gp100:280-288(288V); Drug: Montanide ISA 51 VG; Biological: BMS-936558

A2 - BMS-936558 Without Peptide Vaccine

ACTIVE COMPARATOR

Cohort 6. Each treatment cycle is comprised of 6 doses of BMS-936558 administered every 2 weeks for 12 weeks (cohort 6 has no peptides) (Cycle 1: Weeks 1, 3, 5, 7, 9, and 11; Cycle 2: Weeks 13, 15, 17, 19, 21, and 23) with tumor response assessments at the end of each cycle (during Weeks 12 and 24).

Biological: BMS-936558

Interventions

MART-1 BIOLOGICAL

THIS PEPTIDE REMOVED FROM STUDY ON 1/1/2013. MART-1:26-35(27L) peptide vaccine

Also known as: NSC 709401, peptide vaccine

A1 - Phase I Dose Escalation

NY-ESO-1 BIOLOGICAL

NY-ESO-1 peptide vaccine

Also known as: NSC 717388, peptide vaccine

A1 - Phase I Dose Escalation

gp100:209-217(210M) BIOLOGICAL

THIS PEPTIDE REMOVED FROM STUDY ON 1/1/2013. gp100:209-217(210M) peptide vaccine

Also known as: NSC 683472, peptide vaccine

A1 - Phase I Dose Escalation

gp100:280-288(288V) BIOLOGICAL

gp100:280-288(288V) peptide vaccine

Also known as: NSC 683473, peptide vaccine

A1 - Phase I Dose Escalation

Montanide ISA 51 VG DRUG

Administer peptide vaccine emulsions prepared with Montanide® ISA 51 VG by deep subcutaneous injection.

Also known as: NSC 737063

A1 - Phase I Dose Escalation

BMS-936558 BIOLOGICAL

BMS-936558 is a fully human monoclonal antibody (HuMAb) against programmed death-1 (PD-1). Level 1: 1 mg/kg cohort; Level 2: 3 mg/kg cohort; Level 3: 10 mg/kg cohort; Level 4: 3 mg/kg prior ipi gr 0/1/2 cohort; Level 5: 3 mg/kg prior ipi gr 3 cohort; Level 6: 3 mg/kg BMS-936558 (no peptide vaccine; human leukocyte antigen \[HLA\] unrestricted)

Also known as: NSC 748726, Anti PD-1, antibody, MDX-1106, Immunotherapy

A1 - Phase I Dose Escalation; A2 - BMS-936558 Without Peptide Vaccine

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologic diagnosis of unresectable Stage III or IV melanoma. All melanomas regardless of primary site of disease will be allowed
• Measurable unresectable melanoma at least 1 measurable lesion based on Immune-related Response Criteria (irRC)
• Have failed at least 1 chemotherapy regimen for metastatic disease, and have been treated with up to 2 prior chemotherapy regimens
• HLA-A\*0201 positive as determined by deoxyribonucleic (DNA) allele-specific polymerase chain reaction (PCR) assay; for cohort 5 after amendment 9 and cohort 6, there is no HLA restriction
• Positive staining of tumor tissue with antibodies to 1 or more of the following: human melanoma black 45 (HMB 45) for gp100, NY-ESO-1, and/or MART-1
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Prior chemotherapy or immunotherapy must have been completed at least 4 weeks before study drug administration, and all adverse events have either returned to baseline or stabilized
• Prior treated brain or meningeal metastases must be without magnetic resonance imaging (MRI) evidence of progression for at least 8 weeks and off immunosuppressive doses of systemic steroids (\> 10 mg/day prednisone or equivalent) for at least 2 weeks before study drug administration
• Prior systemic radiation therapy must have been completed at least 4 weeks before study drug administration. Prior focal radiotherapy completed at least 2 weeks before study drug administration. No radiopharmaceuticals (strontium, samarium) within 8 weeks before study drug administration
• Immunosuppressive doses of systemic medications, such as steroids or absorbed topical steroids (doses \> 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks before study drug administration
• Completed nitrosourea treatment at least 6 weeks before administration of any study drug
• Prior surgery that required general anesthesia must be completed at least 2 weeks before study drug administration. Surgery requiring local/epidural anesthesia must be completed at least 72 hours before study drug administration and patients should be recovered.
• Screening laboratory values must meet the following criteria:
• white blood cells (WBCs) ≥ 2000 cells/ µL
• neutrophils ≥ 1500 cells/ µL

You may not qualify if:

• History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs)
• Systemic hypersensitivity to Montanide ISA 51 VG or any vaccine component
• Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or breast
• Patients with any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for patients with vitiligo or resolved childhood asthma/atopy
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Positive tests for hepatitis B virus surface antigen (HBV SAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating active or chronic infection
• Prior therapy with an anti-PD-1, anti-PD-L1, anti-programmed death-ligand-2 (PDL-2), or anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody (or any other antibody targeting T cell co-stimulation pathways)
• Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids
• Underlying medical condition (eg, a condition associated with diarrhea) that, in the Investigator's opinion, would make the administration of either study drug or both study drugs hazardous to the patient or obscure the interpretation of toxicity determination or adverse events
• Pregnant or nursing
• Current participation in another clinical study involving treatment with medications, radiation or surgery, or prior participation in this study

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• National Cancer Institute (NCI): collaborator
• Bristol-Myers Squibb: collaborator
• Medarex: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612-9497, United States

Location

Related Publications (1)

• Weber JS, Kudchadkar RR, Yu B, Gallenstein D, Horak CE, Inzunza HD, Zhao X, Martinez AJ, Wang W, Gibney G, Kroeger J, Eysmans C, Sarnaik AA, Chen YA. Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma. J Clin Oncol. 2013 Dec 1;31(34):4311-8. doi: 10.1200/JCO.2013.51.4802. Epub 2013 Oct 21.

  PMID: 24145345 DERIVED

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Melanoma

Interventions

MART-1 Antigen; Protein Subunit Vaccines; CTAG1B protein, human; montanide ISA 51; Nivolumab; spartalizumab; Antibodies; Immunotherapy

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)

Melanoma-Specific Antigens; Neoplasm Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antigens, Neoplasm; Antigens; Biological Factors; Vaccines, Acellular; Vaccines, Subunit; Vaccines; Biological Products; Complex Mixtures; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Immunomodulation; Biological Therapy; Therapeutics

Study Officials

• Nikhil I. Khushalani, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2010
• First Posted: August 6, 2010
• Study Start: August 4, 2010
• Primary Completion: December 12, 2016
• Study Completion: December 12, 2016
• Last Updated: January 18, 2023

Record last verified: 2023-01

Locations

US (1)