A-dmDT390-bisFv(UCHT1) Fusion Protein With Ionizing Radiation and Pembrolizumab for the Treatment of Stage IV Melanoma

NCT02990416 | Unknown Phase 1 DMC

• 1 other identifier: FDA IND 118558
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the effectiveness of adding a single four-day treatment of the fusion protein A-dmDT390-bisFv(UCHT1) - plus single palliative tumor radiation - with standard of care KEYTRUDA (Pembrolizumab) therapy for the treatment of metastatic melanoma. The results will be measured by comparing the combined therapy to historical data of KEYTRUDA alone.

Conditions

Stage IV Melanoma

Outcome Measures

Primary Outcomes (1)

• Clinical Response primary outcome measure is the change in Progression Free Survival time (PFS).

  The PFS time will be determined as the time from enrollment until the first adverse event (i.e., disease progression or death due to any cause).

  2 months, then at least every 3 months post treatment or until disease progression (maximum 36 months)

Secondary Outcomes (3)

• Changes in Clinical Response Rates

  2 months, then at least every 3 months post treatment or until disease progression (maximum 36 months)

• Tolerability to Treatment

  2 months, then at least every 3 months post treatment or until disease progression (maximum 36 months)

• Overall Survival, OS

  2 months, then at least every 3 months post treatment (maximum 36 months)

Study Arms (1)

A-dmDT390-bisFv(UCHT1)/Radiation/Pembrolizumab

EXPERIMENTAL

A-dmDT390-bisFv(UCHT1): 2.5 µg/kg 2x x 4 days, Ionizing Radiation: single treatment on day five of 14-24 Gy to a tumor, Pembrolizumab: 2 mg/kg IV every 3 weeks

Biological: A-dmDT390-bisFv(UCHT1); Biological: Pembrolizumab; Radiation: Ionizing Radiation

Interventions

A-dmDT390-bisFv(UCHT1) BIOLOGICAL

anti-T cell immunotoxin (antibody targeting CD3 on T-cells tagged with diphtheria toxin without binding domain)

Also known as: Resimmune® (proposed marketing designation)

A-dmDT390-bisFv(UCHT1)/Radiation/Pembrolizumab

Pembrolizumab BIOLOGICAL

A humanized monoclonal immunoglobulin (Ig) G4 antibody directed against human cell surface receptor PD-1 (programmed death-1 or programmed cell death-1) with potential immune checkpoint inhibitory and antineoplastic activities.

Also known as: KEYTRUDA

A-dmDT390-bisFv(UCHT1)/Radiation/Pembrolizumab

Ionizing Radiation RADIATION

Electromagnetic or corpuscular radiation capable of producing ions, directly or indirectly, in its passage through matter.

A-dmDT390-bisFv(UCHT1)/Radiation/Pembrolizumab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must have histologically proven stage IV metastatic melanoma consisting of at least two lesions \>= 1.5 cm that would not occupy the same radiation field. Patients must be treatment naïve except for treatment with BRAF inhibitors. Patients with melanoma must have an anti-DT titer of \<20 μg/ml. Patients with brain metastasis and ocular and mucosal lesions can be enrolled at the discretion of the PI providing that other non-brain and non-ocular metastatic lesions are available as targets for radiation therapy
• Patients must have a performance status of \< 2 on Eastern Cooperative Oncology Group scale (see Appendix). Patients must have fully recovered from toxicity of prior therapy with BRAF inhibitors. Adequate bone marrow function will be defined as ANC \>750 uL, WBC \>1000 uL, platelets \>60,000 uL and Hb \> 9g/dL
• Patients must have:
• bilirubin \< 1.5 mg/dL,
• transaminases \< 2.5 X ULN,
• albumin \> 3 gm/dL,
• creatinine \< 2.0 mg/dL,
• adequate pulmonary function by physical exam and pulse oximetry and adequate cardiac reserve (EF \> 50% normal).
• Patients must have a normal echocardiogram without any evidence of cardiac chamber hypertrophy, dilatation or hypokinesis. The Sponsor must be provided with copies of these tests before Sponsor will approve enrollment. In addition, the sponsor must receive a list of current medications taken by the patient before Sponsor will approve enrollment.
• Patients must give written informed consent prior to registration (see Informed Consent).
• Females and males must be willing to use an approved form of birth control while on this study and for 2 weeks after completion.
• Patients of ages 18-80 are eligible provided they have stage IV melanoma and are negative for BRAF or have failed BRAF inhibitor treatment or if they have failed or are intolerant to other established therapy known to provide clinical benefit for their condition or if they have been adequately consented and agreed to forgo FDA approved clinically meaningful therapy.

You may not qualify if:

• Inability to give informed consent because of psychiatric problems, or complicated medical problems.
• Serious concurrent medical problems, uncontrolled infections, or disseminated intravascular coagulopathy (DIC).
• Congestive heart failure,
• Atrial fibrillation,
• Pulmonary hypertension,
• Anticoagulant drug therapy,
• Thromboembolic events,
• Pregnant or nursing women will be excluded from study.
• History of congestive heart failure.
• History of cirrhosis of the liver.
• Prior treatment with alemtuzumab (Campath) or similar agents or procedures that depress blood T cell counts to below 50% of the lower limit of normal.

Sponsors & Collaborators

• Angimmune LLC: lead
• James Graham Brown Cancer Center: collaborator

Study Sites (1)

James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

Related Publications (4)

• Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science. 2015 Apr 3;348(6230):69-74. doi: 10.1126/science.aaa4971.

  PMID: 25838375 BACKGROUND

• Blake SJ, Ching AL, Kenna TJ, Galea R, Large J, Yagita H, Steptoe RJ. Blockade of PD-1/PD-L1 promotes adoptive T-cell immunotherapy in a tolerogenic environment. PLoS One. 2015 Mar 5;10(3):e0119483. doi: 10.1371/journal.pone.0119483. eCollection 2015.

  PMID: 25741704 BACKGROUND

• Ahmadzadeh M, Johnson LA, Heemskerk B, Wunderlich JR, Dudley ME, White DE, Rosenberg SA. Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood. 2009 Aug 20;114(8):1537-44. doi: 10.1182/blood-2008-12-195792. Epub 2009 May 7.

  PMID: 19423728 BACKGROUND

• Frankel AE, Woo JH, Ahn C, Foss FM, Duvic M, Neville PH, Neville DM. Resimmune, an anti-CD3epsilon recombinant immunotoxin, induces durable remissions in patients with cutaneous T-cell lymphoma. Haematologica. 2015 Jun;100(6):794-800. doi: 10.3324/haematol.2015.123711. Epub 2015 Mar 20.

  PMID: 25795722 RESULT

MeSH Terms

Conditions

Melanoma

Interventions

A-dmDT390-bisFv(UCHT1) protein; pembrolizumab; Radiation, Ionizing

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)

Radiation; Physical Phenomena

Study Officials

• Jason Chesney, MD, PhD

  James Graham Brown Cancer

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brown Cancer Center Clinical Trials Office

CONTACT

502-562-3429; ctobcc@louisville.edu

Study Design

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

Study Record Dates

• First Submitted: November 28, 2016
• First Posted: December 13, 2016
• Study Start: January 1, 2017
• Primary Completion: February 1, 2018
• Study Completion: June 1, 2018
• Last Updated: December 13, 2016

Record last verified: 2016-12

Locations

US (1)