Study of DS-8273a With Nivolumab in Unresectable Stage III or Stage IV Melanoma

NCT02983006 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 15-00906
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety profile, tolerability, and immunoregulatory (pharmacodynamic; PD) activity of DS-8273a administered in combination with nivolumab (anti-PD-1 antibody) to subjects with unresectable Stage III or Stage IV melanoma.

Conditions

Melanoma

Keywords

TRAIL-DR5; DS-8273a; Immunoglobulin gamma-1 (IgG1); Cell mediated cytotoxicity (ADCC); Complement dependent cytotoxicity (CDC); DR5; Immunoglobulin G4 (IgG4); Monoclonal antibody; Programmed Cell Death 1 (PD-1)

Outcome Measures

Primary Outcomes (1)

• Safety (adverse events) of the protocol therapy

  Safety will be evaluated for all treated subjects using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  Up to 2 years

Secondary Outcomes (1)

• Anti-tumor activity of the protocol therapy

  Up to 2 years

Study Arms (1)

DS-8273a & Nivolumab

EXPERIMENTAL

Patient groups (cohorts) will receive a single dose level of DS 8273a \& Nivolumab; DS 8273a will be increased in subsequent cohorts.

Biological: DS-8273a; Biological: Nivolumab

Interventions

DS-8273a BIOLOGICAL

* Starting Dose: 4 mg/ kg IVQ 3 weeks (Cohort 1) * Dose Escalation: 8 mg/kg IV Q 3 weeks (Cohort 2), 16 mg/kg IV Q 3 weeks (Cohort 3), 24 mg/kg IV Q 3 weeks (Cohort 4), 2 mg/kg IV Q 3 weeks (Cohort -1), 4 mg/kg IV Q 3 weeks (Cohort -2)

DS-8273a & Nivolumab

Nivolumab BIOLOGICAL

5 mg/kg IV Q 3 weeks

Also known as: Opdivo

DS-8273a & Nivolumab

Eligibility Criteria

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

You may qualify if:

• \) Signed Written Informed Consent The signed informed consent form prior to the performance of any study related procedures that are not considered part of standard of care.
• \) Target Population
• Subjects who are ipilimumab naïve with progressive unresectable Stage III or Stage IV melanoma; eligible patients may have had prior adjuvant therapy, but not including ipilimumab, and been treated with up to 3 prior treatments for metastatic melanoma \[eg, chemotherapy, other biologic or targeted therapy or Interleukin-2 (IL-2)\].
• Histologic or cytologic confirmation of stage III or stage IV melanoma
• Measurable disease at baseline as assessed by CT and/or MRI
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Screening laboratory values must meet the following criteria and should be obtained within 7 days prior to registration • White blood cell (WBC) ≥ 2000/μL • Neutrophils ≥ 1500/μL
• Platelets ≥ 100 x103/μL
• Hemoglobin \> 9.0 g/dL
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below):
• Female CrCl = (140 - age in years) x weight in kg x 0.85
• x serum creatinine in mg/dL
• Male CrCl = (140 - age in years) x weight in kg x 1.00
• x serum creatinine in mg/dL
• Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) ≤ 3 x ULN Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)

You may not qualify if:

• \) Target Disease Exceptions
• a) Subjects with known or suspected brain metastasis, or brain as the only site of disease are excluded with the following exceptions.
• i) Subjects with controlled brain metastasis (no radiographic progression at least 4 weeks following radiation and/or surgical treatment, off steroids for at least 4 weeks, and have no new or progressing neurological signs or symptoms) will be allowed.
• b) Subjects with a history of prior malignancy with the exception of carcinoma in situ of the cervix or other malignancy diagnosed \> 2 years ago that has undergone potentially curative therapy with no evidence of disease for the last ≥ 2 years and that is deemed by the investigator to be at a low risk of recurrence.
• \) Medical History and Concurrent Diseases
• a) Active autoimmune disease or a history of known or suspected autoimmune disease with the exception of subjects with isolated vitiligo, treated thyroiditis or resolved childhood asthma/atopy.
• b) Known human immunodeficiency virus (HIV), active hepatitis A, or hepatitis B or C infection.
• h) Baseline toxicities from prior anti-cancer treatments \> Grade 1. i) Inability to be venipunctured and/or tolerate venous access. j) Any major surgery within 4 weeks or a diagnostic procedure (eg incision, needle biopsy) within 1 day of study drug administration.
• k) Known drug or alcohol abuse. l) Presence of underlying medical condition that in the opinion of the Investigator or Sponsor could adversely affect the ability of the subject to comply with or tolerate study procedures and/or study therapy, or confound the ability to interpret the tolerability of combined administration of DS-8273A and nivolumab in treated subjects.
• \) Allergies and Adverse Drug Reaction
• a) History of allergy to components of nivolumab or DS-8273A, or known allergy to other antibody therapies.
• \) Sex and Reproductive Status
• WOCBP who are unwilling or unable to use an acceptable method to minimize the risk of pregnancy for the entire study period and for at least 23 weeks after the last dose of investigational product.
• Women who are pregnant or breastfeeding.
• Women with a positive pregnancy test on enrollment or prior to investigational product administration.

Sponsors & Collaborators

• NYU Langone Health: lead
• Bristol-Myers Squibb: collaborator
• Daiichi Sankyo: collaborator

Study Sites (1)

Laura and Isaac Perlmutter Cancer Center

New York, New York, 10016, United States

Location

Related Publications (1)

• Yoshida T, Ichikawa J, Giuroiu I, Laino AS, Hao Y, Krogsgaard M, Vassallo M, Woods DM, Stephen Hodi F, Weber J. C reactive protein impairs adaptive immunity in immune cells of patients with melanoma. J Immunother Cancer. 2020 Apr;8(1):e000234. doi: 10.1136/jitc-2019-000234.

  PMID: 32303612 DERIVED

MeSH Terms

Conditions

Melanoma; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

DS-8273a; Nivolumab

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

• Jeffrey Weber, MD, PhD

  NYU Perlmutter Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2016
• First Posted: December 6, 2016
• Study Start: October 1, 2016
• Primary Completion: December 23, 2019
• Study Completion: January 1, 2021
• Last Updated: October 18, 2021

Record last verified: 2021-10

Locations

US (1)