search
Back to results

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

Primary Purpose

Solid Tumors, Mycosis Fungoides, Melanoma

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
TTI-621 Monotherapy
TTI-621 + PD-1/PD-L1 Inhibitor
TTI-621 + pegylated interferon-α2a
TTI-621 + T-Vec
TTI-621 + radiation
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Solid Tumors focused on measuring CD47, SIRPa, Immunotherapy, Checkpoint inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • City of Hope National Medical Center
  • Laura and Isaac Perlmutter Cancer Center at NYU Langone Health
  • Memorial Sloan Kettering Cancer Center
  • Oregon Health & Science University
  • University of Pittsburgh Medical Center
  • Inova Schar Cancer Institute
  • University of Washington - Seattle Cancer Care Alliance

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

TTI-621 Monotherapy Escalation

TTI-621 Monotherapy (Single Lesion)

TTI-621 Monotherapy (Multiple Lesions)

TTI-621 + PD-1/PD-L1 Inhibitor

TTI-621 + Pegylated Interferon-α2a

TTI-621 + T-Vec

TTI-621 + Radiation

Arm Description

TTI-621 Escalation phase of single or multiple doses of TTI-621 delivered by intratumoral injections (various dose cohorts).

TTI-621 Single Lesion Injection Expansion Cohort

TTI-621 Multiple Lesion Injections Expansion Cohort

Combination Therapy Expansion Cohort of TTI-621 plus PD-1/PD-L1 Inhibitor

Combination Therapy Expansion Cohort of TTI-621 plus Pegylated Interferon-α2a

Combination Therapy Expansion Cohort of TTI-621 plus T-Vec

Combination Therapy Expansion Cohort of TTI-621 plus Radiation Therapy

Outcomes

Primary Outcome Measures

Optimal TTI-621 delivery regimen
Defining the optimal TTI-621 delivery regimen in subjects with advanced percutaneously-accessible cancer

Secondary Outcome Measures

Frequency and severity of adverse events
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
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

Full Information

First Posted
August 26, 2016
Last Updated
March 31, 2023
Sponsor
Pfizer
search

1. Study Identification

Unique Protocol Identification Number
NCT02890368
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Terminated
Study Start Date
September 2016 (undefined)
Primary Completion Date
March 31, 2020 (Actual)
Study Completion Date
March 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Tumors, Mycosis Fungoides, Melanoma, Merkel-cell Carcinoma, Squamous Cell Carcinoma, Breast Carcinoma, Human Papillomavirus-Related Malignant Neoplasm, Soft Tissue Sarcoma
Keywords
CD47, SIRPa, Immunotherapy, Checkpoint inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
56 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TTI-621 Monotherapy Escalation
Arm Type
Experimental
Arm Description
TTI-621 Escalation phase of single or multiple doses of TTI-621 delivered by intratumoral injections (various dose cohorts).
Arm Title
TTI-621 Monotherapy (Single Lesion)
Arm Type
Experimental
Arm Description
TTI-621 Single Lesion Injection Expansion Cohort
Arm Title
TTI-621 Monotherapy (Multiple Lesions)
Arm Type
Experimental
Arm Description
TTI-621 Multiple Lesion Injections Expansion Cohort
Arm Title
TTI-621 + PD-1/PD-L1 Inhibitor
Arm Type
Experimental
Arm Description
Combination Therapy Expansion Cohort of TTI-621 plus PD-1/PD-L1 Inhibitor
Arm Title
TTI-621 + Pegylated Interferon-α2a
Arm Type
Experimental
Arm Description
Combination Therapy Expansion Cohort of TTI-621 plus Pegylated Interferon-α2a
Arm Title
TTI-621 + T-Vec
Arm Type
Experimental
Arm Description
Combination Therapy Expansion Cohort of TTI-621 plus T-Vec
Arm Title
TTI-621 + Radiation
Arm Type
Experimental
Arm Description
Combination Therapy Expansion Cohort of TTI-621 plus Radiation Therapy
Intervention Type
Drug
Intervention Name(s)
TTI-621 Monotherapy
Other Intervention Name(s)
SIRPα-IgG1 Fc
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
TTI-621 + PD-1/PD-L1 Inhibitor
Other Intervention Name(s)
SIRPα-IgG1 Fc + PD-1/PD-L1 Inhibitor
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
TTI-621 + pegylated interferon-α2a
Other Intervention Name(s)
SIRPα-IgG1 Fc + pegylated interferon-α2a
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
TTI-621 + T-Vec
Other Intervention Name(s)
SIRPα-IgG1 Fc + talimogene laherparepvec
Intervention Description
TTI-621 will be given in combination with talimogene laherparepvec (T-Vec). Subjects in this cohort must have unresectable melanoma.
Intervention Type
Other
Intervention Name(s)
TTI-621 + radiation
Other Intervention Name(s)
SIRPα-IgG1 Fc + radiation
Intervention Description
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).
Primary Outcome Measure Information:
Title
Optimal TTI-621 delivery regimen
Description
Defining the optimal TTI-621 delivery regimen in subjects with advanced percutaneously-accessible cancer
Time Frame
10 months
Secondary Outcome Measure Information:
Title
Frequency and severity of adverse events
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
Time Frame
15 months
Title
Preliminary evidence of anti-tumor activity of TTI-621
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
Time Frame
15 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Laura and Isaac Perlmutter Cancer Center at NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15237
Country
United States
Facility Name
Inova Schar Cancer Institute
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
University of Washington - Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34627593
Citation
Querfeld C, Thompson JA, Taylor MH, DeSimone JA, Zain JM, Shustov AR, Johns C, McCann S, Lin GHY, Petrova PS, Uger RA, Molloy N, Shou Y, Akilov OE. Intralesional TTI-621, a novel biologic targeting the innate immune checkpoint CD47, in patients with relapsed or refractory mycosis fungoides or Sezary syndrome: a multicentre, phase 1 study. Lancet Haematol. 2021 Nov;8(11):e808-e817. doi: 10.1016/S2352-3026(21)00271-4. Epub 2021 Oct 7.
Results Reference
derived
PubMed Identifier
34519839
Citation
Kruglov O, Johnson LDS, Minic A, Jordan K, Uger RA, Wong M, Sievers EL, Shou Y, Akilov OE. The pivotal role of cytotoxic NK cells in mediating the therapeutic effect of anti-CD47 therapy in mycosis fungoides. Cancer Immunol Immunother. 2022 Apr;71(4):919-932. doi: 10.1007/s00262-021-03051-x. Epub 2021 Sep 14.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs