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Trial of Intratumoral Injections of TTI-621 in Subjects With Relapsed and Refractory Solid Tumors and Mycosis Fungoides

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ClinicalTrials.gov Identifier: NCT02890368
Recruitment Status : Recruiting
First Posted : September 7, 2016
Last Update Posted : April 11, 2018
Sponsor:
Information provided by (Responsible Party):
Trillium Therapeutics Inc.

Brief Summary:

This is a multicenter, open-label, phase 1 study conducted to test intratumoral injections of TTI-621 in subjects that have relapsed and refractory percutaneously accessible solid tumors or mycosis fungoides.

The study will be performed in two different parts. Part 1 is the Dose Escalation phase and Part 2 is the Dose Expansion phase.

The purpose of this study is to characterize the safety profile of TTI-621 and to determine the optimal dose and delivery schedule of TTI-621. In addition, the safety and antitumor activity of TTI-621 will be evaluated in combination with other anti-cancer agents or radiation.


Condition or disease Intervention/treatment Phase
Solid Tumors Mycosis Fungoides Melanoma Merkel-cell Carcinoma Squamous Cell Carcinoma Breast Carcinoma Human Papillomavirus-Related Malignant Neoplasm Soft Tissue Sarcoma Drug: TTI-621 Monotherapy Drug: TTI-621 + PD-1/PD-L1 Inhibitor Drug: TTI-621 + pegylated interferon-α2a Other: TTI-621 + T-Vec Other: TTI-621 + radiation Phase 1

Detailed Description:

This is a multicenter, open-label, phase 1 study conducted to test intratumoral injections of TTI-621 in patients that have relapsed and refractory percutaneously accessible solid tumors or mycosis fungoides.

TTI-621 (SIRPα-IgG1 Fc) is a soluble recombinant fusion protein created by directly linking the sequences encoding the N-terminal CD47 binding domain of human SIRPα with the Fc domain of human immunoglobulin (IgG1). TTI-621 acts by binding human CD47 and preventing it from delivering an inhibitory "do not eat" (antiphagocytic) signal to macrophages.

The study will be performed in two different parts: Dose Escalation and Dose Expansion.

During the escalation part of the study, TTI-621 was studied at 3 different dose levels and at different dosing frequencies to characterize safety, tolerability, pharmacokinetics, and to determine the maximum tolerated dose (MTD).

During the expansion part of the study, TTI-621 will be studied in an expanded group of patients at the maximum feasible dosing regimen determined in the escalation phase. After completion of their initial assigned therapy, subjects may receive continuation with TTI-621. The expansion phase will further define safety and characterize efficacy of TTI-621 alone and in combination with other anti-cancer therapies.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Dose Escalation Trial of Intratumoral Injections of TTI-621 in Subjects With Relapsed and Refractory Percutaneously-Accessible Solid Tumors and Mycosis Fungoides
Study Start Date : September 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2019


Arm Intervention/treatment
Experimental: TTI-621 Monotherapy Escalation
TTI-621 Escalation phase of single or multiple doses of TTI-621 delivered by intratumoral injections (various dose cohorts).
Drug: TTI-621 Monotherapy
TTI-621 (SIRPα-IgG1 Fc) is a soluble recombinant fusion protein created by directly linking the sequences encoding the N-terminal CD47 binding domain of human SIRPα with the Fc domain of human immunoglobulin (IgG1). TTI-621 acts by binding human CD47 and preventing it from delivering an inhibitory "do not eat" (antiphagocytic) signal to macrophages.
Other Name: SIRPα-IgG1 Fc
Experimental: TTI-621 Monotherapy (Single Lesion)
TTI-621 Single Lesion Injection Expansion Cohort
Drug: TTI-621 Monotherapy
TTI-621 (SIRPα-IgG1 Fc) is a soluble recombinant fusion protein created by directly linking the sequences encoding the N-terminal CD47 binding domain of human SIRPα with the Fc domain of human immunoglobulin (IgG1). TTI-621 acts by binding human CD47 and preventing it from delivering an inhibitory "do not eat" (antiphagocytic) signal to macrophages.
Other Name: SIRPα-IgG1 Fc
Experimental: TTI-621 Monotherapy (Multiple Lesions)
TTI-621 Multiple Lesion Injections Expansion Cohort
Drug: TTI-621 Monotherapy
TTI-621 (SIRPα-IgG1 Fc) is a soluble recombinant fusion protein created by directly linking the sequences encoding the N-terminal CD47 binding domain of human SIRPα with the Fc domain of human immunoglobulin (IgG1). TTI-621 acts by binding human CD47 and preventing it from delivering an inhibitory "do not eat" (antiphagocytic) signal to macrophages.
Other Name: SIRPα-IgG1 Fc
Experimental: TTI-621 + PD-1/PD-L1 Inhibitor
Combination Therapy Expansion Cohort of TTI-621 plus PD-1/PD-L1 Inhibitor
Drug: TTI-621 + PD-1/PD-L1 Inhibitor
TTI-621 will be given in combination with one of the following programmed death-1 (PD-1) or programmed death-ligand-1 (PD-L1) inhibitors: nivolumab, pembrolizumab, durvalumab, avelumab, or atezolizumab administered on Day 1. Subjects in this cohort must have a cancer diagnosis for which a PD-1/PD-L1 inhibitor is approved by the FDA or listed in the National Comprehensive Cancer Network (NCCN) Guidelines.
Other Name: SIRPα-IgG1 Fc + PD-1/PD-L1 Inhibitor
Experimental: TTI-621 + Pegylated Interferon-α2a
Combination Therapy Expansion Cohort of TTI-621 plus Pegylated Interferon-α2a
Drug: TTI-621 + pegylated interferon-α2a
TTI-621 will be given in combination with pegylated interferon-α2a. Subjects in this cohort must have a cancer diagnosis for which pegylated interferon-α2a is approved by the FDA or listed in the National Comprehensive Cancer Network (NCCN) Guidelines.
Other Name: SIRPα-IgG1 Fc + pegylated interferon-α2a
Experimental: TTI-621 + T-Vec
Combination Therapy Expansion Cohort of TTI-621 plus T-Vec
Other: TTI-621 + T-Vec
TTI-621 will be given in combination with talimogene laherparepvec (T-Vec). Subjects in this cohort must have unresectable melanoma.
Other Name: SIRPα-IgG1 Fc + talimogene laherparepvec
Experimental: TTI-621 + Radiation
Combination Therapy Expansion Cohort of TTI-621 plus Radiation Therapy
Other: TTI-621 + radiation
TTI-621 will be given following radiation to the target plasmacytoma. Subjects in this cohort must have relapsed multiple myeloma with bony or soft tissue plasmacytoma(s).
Other Name: SIRPα-IgG1 Fc + radiation



Primary Outcome Measures :
  1. Optimal TTI-621 delivery regimen [ Time Frame: 10 months ]
    Defining the optimal TTI-621 delivery regimen in subjects with advanced percutaneously-accessible cancer


Secondary Outcome Measures :
  1. Frequency and severity of adverse events [ Time Frame: 15 months ]
    Safety of TTI-621 when given to subjects with relapsed and refractory percutaneously-accessible solid tumors and Mycosis Fungoides alone and in combination with other anti-cancer drugs or radiation

  2. Preliminary evidence of anti-tumor activity of TTI-621 [ Time Frame: 15 months ]
    Preliminary evidence of anti-tumor activity of TTI-621 when given to subjects with relapsed and refractory percutaneously-accessible solid tumors and Mycosis Fungoides alone and in combination with other anti-cancer drugs or radiation



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically documented, injectable cancer lesion (limited to solid tumors and mycosis fungoides)
  • Adequate renal function
  • Adequate coagulation function
  • Adequate hepatic function
  • Disease that has progressed on standard therapy or for whom there is no other therapy option available

Exclusion Criteria:

  • Central nervous system involvement
  • Significant cardiovascular disease
  • Active autoimmune disease
  • Active hepatitis B or C or a history of HIV infection
  • Uncontrolled infection
  • History of hemolytic anemia or bleeding diathesis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02890368


Contacts
Contact: Theresa Thompson theresa2@trilliumtherapeutics.com
Contact: Penka Petrova, PhD 416-595-0627 ext 234 Penka@trilliumtherapeutics.com

Locations
United States, California
City of Hope National Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Jaemee Bautista    626-218-3033    jbautista@coh.org   
Contact: Linda Lee    626-256-4673 ext 89165    Linlee@coh.org   
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Knight Clinical Trials Information Line    503-494-1080      
United States, Pennsylvania
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15237
Contact: Sue McCann    412-864-3681    mccannsa@upmc.edu   
United States, Washington
University of Washington - Seattle Cancer Care Alliance Recruiting
Seattle, Washington, United States, 98109
Contact: Shahaan Smith    206-606-6448    sjsmith@seattlecca.org   
Sponsors and Collaborators
Trillium Therapeutics Inc.
Investigators
Study Director: Penka Petrova, PhD Trillium Therapeutics Inc.

Additional Information:
Responsible Party: Trillium Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT02890368     History of Changes
Other Study ID Numbers: TTI-621-02
First Posted: September 7, 2016    Key Record Dates
Last Update Posted: April 11, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Trillium Therapeutics Inc.:
CD47
SIRPa
Immunotherapy
Checkpoint inhibitor

Additional relevant MeSH terms:
Mycoses
Mycosis Fungoides
Carcinoma
Carcinoma, Squamous Cell
Sarcoma
Neoplasms
Breast Neoplasms
Carcinoma, Merkel Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Neoplasms, Connective and Soft Tissue
Lymphoma, T-Cell, Cutaneous
Lymphoma, T-Cell
Lymphoma, Non-Hodgkin
Lymphoma
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site
Breast Diseases
Skin Diseases
Polyomavirus Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Carcinoma, Neuroendocrine
Neuroendocrine Tumors
Neuroectodermal Tumors