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

March 31, 2023 updated by: Pfizer

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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

Enrollment (Actual)

56

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope National Medical Center
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10016
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone Health
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15237
        • University of Pittsburgh Medical Center
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Inova Schar Cancer Institute
    • Washington
      • Seattle, Washington, United States, 98109
        • University of Washington - Seattle Cancer Care Alliance

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • SIRPα-IgG1 Fc + radiation

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
15 months
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
15 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2016

Primary Completion (Actual)

March 31, 2020

Study Completion (Actual)

March 31, 2020

Study Registration Dates

First Submitted

August 26, 2016

First Submitted That Met QC Criteria

August 31, 2016

First Posted (Estimate)

September 7, 2016

Study Record Updates

Last Update Posted (Actual)

April 5, 2023

Last Update Submitted That Met QC Criteria

March 31, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TTI-621-02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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