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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02890368
Recruitment Status : Terminated
First Posted : September 7, 2016
Last Update Posted : May 15, 2020
Sponsor:
Information provided by (Responsible Party):
Trillium Therapeutics Inc.

Tracking Information
First Submitted Date  ICMJE August 26, 2016
First Posted Date  ICMJE September 7, 2016
Last Update Posted Date May 15, 2020
Study Start Date  ICMJE September 2016
Actual Primary Completion Date March 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 25, 2018)
Optimal TTI-621 delivery regimen [ Time Frame: 10 months ]
Defining the optimal TTI-621 delivery regimen in subjects with advanced percutaneously-accessible cancer
Original Primary Outcome Measures  ICMJE
 (submitted: August 31, 2016)
Dose Limiting Toxicity (DLT) [ Time Frame: 1 month ]
Number of participants with a DLT
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 25, 2018)
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial of Intratumoral Injections of TTI-621 in Subjects With Relapsed and Refractory Solid Tumors and Mycosis Fungoides
Official Title  ICMJE 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
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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Solid Tumors
  • Mycosis Fungoides
  • Melanoma
  • Merkel-cell Carcinoma
  • Squamous Cell Carcinoma
  • Breast Carcinoma
  • Human Papillomavirus-Related Malignant Neoplasm
  • Soft Tissue Sarcoma
Intervention  ICMJE
  • 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
  • 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
  • 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
  • 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
  • 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
Study Arms  ICMJE
  • Experimental: TTI-621 Monotherapy Escalation
    TTI-621 Escalation phase of single or multiple doses of TTI-621 delivered by intratumoral injections (various dose cohorts).
    Intervention: Drug: TTI-621 Monotherapy
  • Experimental: TTI-621 Monotherapy (Single Lesion)
    TTI-621 Single Lesion Injection Expansion Cohort
    Intervention: Drug: TTI-621 Monotherapy
  • Experimental: TTI-621 Monotherapy (Multiple Lesions)
    TTI-621 Multiple Lesion Injections Expansion Cohort
    Intervention: Drug: TTI-621 Monotherapy
  • Experimental: TTI-621 + PD-1/PD-L1 Inhibitor
    Combination Therapy Expansion Cohort of TTI-621 plus PD-1/PD-L1 Inhibitor
    Intervention: Drug: TTI-621 + PD-1/PD-L1 Inhibitor
  • Experimental: TTI-621 + Pegylated Interferon-α2a
    Combination Therapy Expansion Cohort of TTI-621 plus Pegylated Interferon-α2a
    Intervention: Drug: TTI-621 + pegylated interferon-α2a
  • Experimental: TTI-621 + T-Vec
    Combination Therapy Expansion Cohort of TTI-621 plus T-Vec
    Intervention: Other: TTI-621 + T-Vec
  • Experimental: TTI-621 + Radiation
    Combination Therapy Expansion Cohort of TTI-621 plus Radiation Therapy
    Intervention: Other: TTI-621 + radiation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: May 13, 2020)
56
Original Estimated Enrollment  ICMJE
 (submitted: August 31, 2016)
54
Actual Study Completion Date  ICMJE March 31, 2020
Actual Primary Completion Date March 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02890368
Other Study ID Numbers  ICMJE TTI-621-02
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Trillium Therapeutics Inc.
Study Sponsor  ICMJE Trillium Therapeutics Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Trillium Therapeutics Inc.
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP