Clinical Trials /

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

NCT02890368

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
  • Melanoma
  • Multiple Myeloma
  • Mycosis Fungoides
  • Plasmacytoma
Recruiting Status:

Terminated

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT02890368

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: TTI-621-02
  • NCT ID: NCT02890368

Conditions

  • Solid Tumors
  • Mycosis Fungoides
  • Melanoma
  • Merkel-cell Carcinoma
  • Squamous Cell Carcinoma
  • Breast Carcinoma
  • Human Papillomavirus-Related Malignant Neoplasm
  • Soft Tissue Sarcoma

Interventions

DrugSynonymsArms
TTI-621 MonotherapySIRPα-IgG1 FcTTI-621 Monotherapy (Multiple Lesions)
TTI-621 + PD-1/PD-L1 InhibitorSIRPα-IgG1 Fc + PD-1/PD-L1 InhibitorTTI-621 + PD-1/PD-L1 Inhibitor
TTI-621 + pegylated interferon-α2aSIRPα-IgG1 Fc + pegylated interferon-α2aTTI-621 + Pegylated Interferon-α2a

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
TTI-621 Monotherapy EscalationExperimentalTTI-621 Escalation phase of single or multiple doses of TTI-621 delivered by intratumoral injections (various dose cohorts).
  • TTI-621 Monotherapy
TTI-621 Monotherapy (Single Lesion)ExperimentalTTI-621 Single Lesion Injection Expansion Cohort
  • TTI-621 Monotherapy
TTI-621 Monotherapy (Multiple Lesions)ExperimentalTTI-621 Multiple Lesion Injections Expansion Cohort
  • TTI-621 Monotherapy
TTI-621 + PD-1/PD-L1 InhibitorExperimentalCombination Therapy Expansion Cohort of TTI-621 plus PD-1/PD-L1 Inhibitor
  • TTI-621 + PD-1/PD-L1 Inhibitor
TTI-621 + Pegylated Interferon-α2aExperimentalCombination Therapy Expansion Cohort of TTI-621 plus Pegylated Interferon-α2a
  • TTI-621 + pegylated interferon-α2a
TTI-621 + T-VecExperimentalCombination Therapy Expansion Cohort of TTI-621 plus T-Vec
    TTI-621 + RadiationExperimentalCombination Therapy Expansion Cohort of TTI-621 plus Radiation Therapy

      Eligibility 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
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Optimal TTI-621 delivery regimen
      Time Frame:10 months
      Safety Issue:
      Description:Defining the optimal TTI-621 delivery regimen in subjects with advanced percutaneously-accessible cancer

      Secondary Outcome Measures

      Measure:Frequency and severity of adverse events
      Time Frame:15 months
      Safety Issue:
      Description: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
      Measure:Preliminary evidence of anti-tumor activity of TTI-621
      Time Frame:15 months
      Safety Issue:
      Description: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

      Details

      Phase:Phase 1
      Primary Purpose:Interventional
      Overall Status:Terminated
      Lead Sponsor:Trillium Therapeutics Inc.

      Trial Keywords

      • CD47
      • SIRPa
      • Immunotherapy
      • Checkpoint inhibitor

      Last Updated

      May 15, 2020