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MelanomaPhase 1NCT02983006

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

A Phase 1 study testing DS-8273a and Nivolumab in people with Melanoma, run by NYU Langone Health at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma
What is being tested?
DS-8273a and Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteUnited States
Study dates
Oct 2016to 1 Jan 2021
Phase
Phase 1
Are there results?
None posted in the registry

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

  • 1) 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.
  • 2) 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
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  • 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
  • 72 x serum creatinine in mg/dL
  • Male CrCl = (140 - age in years) x weight in kg x 1.00
  • 72 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)
  • 3) Age and Reproductive Status Men and women ≥ 18 years old
  • <!-- -->
  • Men and women of childbearing potential (WOCBP) must be using an acceptable method of contraception to avoid pregnancy throughout the study, and for women at least 23 weeks after the last dose of investigational product and for men at least 31 weeks after the last dose of investigational product in such a manner that the risk of pregnancy is minimized. See Section 3.3.3 for the definition of WOCBP.
  • Women must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of investigational product.

Who cannot join

  • 1) Target Disease Exceptions
  • Subjects with known or suspected brain metastasis, or brain as the only site of disease are excluded with the following exceptions.
  • 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.
  • 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.
  • 2) Medical History and Concurrent Diseases
  • 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.
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  • Known human immunodeficiency virus (HIV), active hepatitis A, or hepatitis B or C infection.
  • Evidence of active infection that requires anti-bacterial, anti-viral, or anti-fungal therapy ≤ 7 days prior to initiation of study drug therapy d) History of acute diverticulitis within the last 6 months, or current chronic diarrhea e) Active peptic ulcer disease even if asymptomatic f) Prior organ allograft or allogenic bone marrow transplantation g) Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following: i) Myocardial infarction within the past 6 months ii) Uncontrolled angina within the past 6 months iii) Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation or Torsades de pointes). Controlled atrial fibrillation by itself is not an exclusion criterion.
  • 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.
  • 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.
  • 3) Allergies and Adverse Drug Reaction
  • History of allergy to components of nivolumab or DS-8273A, or known allergy to other antibody therapies.
  • 4) 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.
  • Sexually active fertile men not using effective birth control if their partners are WOCBP.
  • 5) Prohibited Prior Treatments and/or Therapies
  • Exposure to any investigational drug within 4 weeks of study drug administration.
  • Any anti-cancer therapy (eg, chemotherapy, biologics, radiotherapy, or hormonal treatment) within 4 weeks or at least 5 half-lives (whichever is longer) of study drug administration.
  • Prior therapy with an anti-PD-1/PD-L1 antibody or a TRAIL-DR5 antibody d) Concurrent chemotherapy, hormonal therapy, immunotherapy regimens, or radiation therapy, standard or investigational.
  • 6) Other Exclusion Criteria
  • Prisoners or subjects who are involuntarily incarcerated
  • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Laura and Isaac Perlmutter Cancer Center

    New York, New York, 10016

Other trials in United States

About this study

Official title: A Phase 1 Study of TRAIL-DR5 Antibody DS-8273a Administered in Combination With Nivolumab in Subjects With Unresectable Stage III or Stage IV Melanoma

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.

Read the detailed description

Principal investigator hypothesize that TRAIL D5 antibody DS-8273a administered in combination with nivolumab will be well tolerated and that the addition of DS-8273a will augment the clinical efficacy of nivolumab.

Conditions
Melanoma
Being tested
DS-8273a, Nivolumab
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)
Medical subject headings
Melanoma, Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DS-8273aBiological

    • 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)

  • NivolumabBiological

    Also called Opdivo

    5 mg/kg IV Q 3 weeks

Study groups in NCT02983006
Study groupRoleWhat they receive
DS-8273a & NivolumabExperimentalPatient groups (cohorts) will receive a single dose level of DS 8273a \& Nivolumab; DS 8273a will be increased in subsequent cohorts.
Receives: Biological: DS-8273a; Biological: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Up to 2 years

Secondary outcomes (1)

  1. Anti-tumor activity of the protocol therapy

    Tumor response will be determined for all subjects by RECIST 1.1 as well as by immune-related response criteria

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Dec 2016 (estimated)
  2. Study startOct 2016
  3. Primary completion23 Dec 2019
  4. Study completion1 Jan 2021

Resources

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02983006
Sponsor's protocol ID
15-00906
Status last verified
Oct 2021
First submitted
2 Dec 2016
Last updated
18 Oct 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 32303612

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing DS-8273a and Nivolumab in people with Melanoma, run by NYU Langone Health at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety (adverse events) of the protocol therapy (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02983006, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2021.

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