Trial of Intratumoral Injections of TTI-621 in Subjects With Relapsed and Refractory Solid Tumors and Mycosis Fungoides
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
1 other identifier
interventional
56
1 country
7
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Sep 2016
Typical duration for phase_1
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 26, 2016
CompletedStudy Start
First participant enrolled
September 1, 2016
CompletedFirst Posted
Study publicly available on registry
September 7, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
March 31, 2020
CompletedApril 5, 2023
March 1, 2023
3.6 years
August 26, 2016
March 31, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Optimal TTI-621 delivery regimen
Defining the optimal TTI-621 delivery regimen in subjects with advanced percutaneously-accessible cancer
10 months
Secondary Outcomes (2)
Frequency and severity of adverse events
15 months
Preliminary evidence of anti-tumor activity of TTI-621
15 months
Study Arms (7)
TTI-621 Monotherapy Escalation
EXPERIMENTALTTI-621 Escalation phase of single or multiple doses of TTI-621 delivered by intratumoral injections (various dose cohorts).
TTI-621 Monotherapy (Single Lesion)
EXPERIMENTALTTI-621 Single Lesion Injection Expansion Cohort
TTI-621 Monotherapy (Multiple Lesions)
EXPERIMENTALTTI-621 Multiple Lesion Injections Expansion Cohort
TTI-621 + PD-1/PD-L1 Inhibitor
EXPERIMENTALCombination Therapy Expansion Cohort of TTI-621 plus PD-1/PD-L1 Inhibitor
TTI-621 + Pegylated Interferon-α2a
EXPERIMENTALCombination Therapy Expansion Cohort of TTI-621 plus Pegylated Interferon-α2a
TTI-621 + T-Vec
EXPERIMENTALCombination Therapy Expansion Cohort of TTI-621 plus T-Vec
TTI-621 + Radiation
EXPERIMENTALCombination Therapy Expansion Cohort of TTI-621 plus Radiation Therapy
Interventions
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.
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.
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.
TTI-621 will be given in combination with talimogene laherparepvec (T-Vec). Subjects in this cohort must have unresectable melanoma.
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).
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
Study Sites (7)
City of Hope National Medical Center
Duarte, California, 91010, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York, 10016, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Oregon Health & Science University
Portland, Oregon, 97239, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15237, United States
Inova Schar Cancer Institute
Fairfax, Virginia, 22031, United States
University of Washington - Seattle Cancer Care Alliance
Seattle, Washington, 98109, United States
Related Publications (2)
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.
PMID: 34627593DERIVEDKruglov 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.
PMID: 34519839DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 26, 2016
First Posted
September 7, 2016
Study Start
September 1, 2016
Primary Completion
March 31, 2020
Study Completion
March 31, 2020
Last Updated
April 5, 2023
Record last verified: 2023-03
Data Sharing
- IPD Sharing
- Will not share