Solid TumorsPhase 1NCT02890368
Trial of Intratumoral Injections of TTI-621 in Subjects With Relapsed and Refractory Solid Tumors and Mycosis Fungoides
A Phase 1 study testing TTI-621 Monotherapy, TTI-621 + PD-1/PD-L1 Inhibitor and TTI-621 + pegylated interferon-α2a in people with Solid Tumors and Mycosis Fungoides, run by Pfizer at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors, Mycosis Fungoides, Melanoma
- What is being tested?
- TTI-621 Monotherapy, TTI-621 + PD-1/PD-L1 Inhibitor and TTI-621 + pegylated interferon-α2a
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 7 sitesUnited States
- Study dates
- Sep 2016to 31 Mar 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
City of Hope National Medical Center
Duarte, California, 91010
Inova Schar Cancer Institute
Fairfax, Virginia, 22031
Laura and Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York, 10016
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15237
Oregon Health & Science University
Portland, Oregon, 97239
University of Washington - Seattle Cancer Care Alliance
Seattle, Washington, 98109
About this study
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
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.
Read the 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.
- Conditions
- Solid Tumors, Mycosis Fungoides, Melanoma, Merkel-cell Carcinoma, Squamous Cell Carcinoma, Breast Carcinoma
- Being tested
- TTI-621 Monotherapy, TTI-621 + PD-1/PD-L1 Inhibitor, TTI-621 + pegylated interferon-α2a, TTI-621 + T-Vec, TTI-621 + radiation
- Keywords
- CD47, SIRPa, Immunotherapy, Checkpoint inhibitor
- Medical subject headings
- Mycosis Fungoides, Melanoma, Carcinoma, Merkel Cell, Carcinoma, Squamous Cell, Breast Neoplasms, Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TTI-621 MonotherapyDrug
Also called SIRPα-IgG1 Fc
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 + PD-1/PD-L1 InhibitorDrug
Also called SIRPα-IgG1 Fc + 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.
TTI-621 + pegylated interferon-α2aDrug
Also called SIRPα-IgG1 Fc + 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.
TTI-621 + T-VecOther
Also called SIRPα-IgG1 Fc + talimogene laherparepvec
TTI-621 will be given in combination with talimogene laherparepvec (T-Vec). Subjects in this cohort must have unresectable melanoma.
TTI-621 + radiationOther
Also called SIRPα-IgG1 Fc + 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).
| Study group | Role | What they receive |
|---|---|---|
| TTI-621 Monotherapy Escalation | Experimental | TTI-621 Escalation phase of single or multiple doses of TTI-621 delivered by intratumoral injections (various dose cohorts). Receives: Drug: TTI-621 Monotherapy |
| TTI-621 Monotherapy (Single Lesion) | Experimental | TTI-621 Single Lesion Injection Expansion Cohort Receives: Drug: TTI-621 Monotherapy |
| TTI-621 Monotherapy (Multiple Lesions) | Experimental | TTI-621 Multiple Lesion Injections Expansion Cohort Receives: Drug: TTI-621 Monotherapy |
| TTI-621 + PD-1/PD-L1 Inhibitor | Experimental | Combination Therapy Expansion Cohort of TTI-621 plus PD-1/PD-L1 Inhibitor Receives: Drug: TTI-621 + PD-1/PD-L1 Inhibitor |
| TTI-621 + Pegylated Interferon-α2a | Experimental | Combination Therapy Expansion Cohort of TTI-621 plus Pegylated Interferon-α2a Receives: Drug: TTI-621 + pegylated interferon-α2a |
| TTI-621 + T-Vec | Experimental | Combination Therapy Expansion Cohort of TTI-621 plus T-Vec Receives: Other: TTI-621 + T-Vec |
| TTI-621 + Radiation | Experimental | Combination Therapy Expansion Cohort of TTI-621 plus Radiation Therapy Receives: Other: TTI-621 + radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Optimal TTI-621 delivery regimen
Defining the optimal TTI-621 delivery regimen in subjects with advanced percutaneously-accessible cancer
Measured: 10 months
Secondary outcomes (2)
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
Measured: 15 months
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
Measured: 15 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2016 (estimated)
- Study startSep 2016
- Primary completion31 Mar 2020
- Study completion31 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02890368
- Sponsor's protocol ID
- TTI-621-02
- Status last verified
- Mar 2023
- First submitted
- 26 Aug 2016
- Last updated
- 5 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 34627593Kruglov 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.
PubMed 34519839
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02890368
- Acronym / sponsor ID
- TTI-621-02
- Conditions
- Solid Tumors, Mycosis Fungoides, Melanoma, Merkel-cell Carcinoma, Squamous Cell Carcinoma, Breast Carcinoma
- Keywords
- CD47, SIRPa, Immunotherapy, Checkpoint inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 56 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- Sep 2016
- Primary completion
- 31 Mar 2020 (actual)
- Study completion
- 31 Mar 2020 (actual)
- First posted
- 7 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| TTI-621 Monotherapy Escalation | Experimental | Drug: TTI-621 MonotherapyTTI-621 Escalation phase of single or multiple doses of TTI-621 delivered by intratumoral injections (various dose cohorts). |
| TTI-621 Monotherapy (Single Lesion) | Experimental | Drug: TTI-621 MonotherapyTTI-621 Single Lesion Injection Expansion Cohort |
| TTI-621 Monotherapy (Multiple Lesions) | Experimental | Drug: TTI-621 MonotherapyTTI-621 Multiple Lesion Injections Expansion Cohort |
| TTI-621 + PD-1/PD-L1 Inhibitor | Experimental | Drug: TTI-621 + PD-1/PD-L1 InhibitorCombination Therapy Expansion Cohort of TTI-621 plus PD-1/PD-L1 Inhibitor |
| TTI-621 + Pegylated Interferon-α2a | Experimental | Drug: TTI-621 + pegylated interferon-α2aCombination Therapy Expansion Cohort of TTI-621 plus Pegylated Interferon-α2a |
| TTI-621 + T-Vec | Experimental | Other: TTI-621 + T-VecCombination Therapy Expansion Cohort of TTI-621 plus T-Vec |
| TTI-621 + Radiation | Experimental | Other: TTI-621 + radiationCombination Therapy Expansion Cohort of TTI-621 plus Radiation Therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- Central nervous system involvement
- Significant cardiovascular disease
- Active autoimmune disease
- Active hepatitis B or C or a history of HIV infection
- Uncontrolled infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TTI-621 MonotherapyAlso: SIRPα-IgG1 FcTTI-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. | Drug | TTI-621 Monotherapy (Multiple Lesions), TTI-621 Monotherapy (Single Lesion), TTI-621 Monotherapy Escalation |
| TTI-621 + PD-1/PD-L1 InhibitorAlso: SIRPα-IgG1 Fc + PD-1/PD-L1 InhibitorTTI-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. | Drug | TTI-621 + PD-1/PD-L1 Inhibitor |
| TTI-621 + pegylated interferon-α2aAlso: SIRPα-IgG1 Fc + pegylated interferon-α2aTTI-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. | Drug | TTI-621 + Pegylated Interferon-α2a |
| TTI-621 + T-VecAlso: SIRPα-IgG1 Fc + talimogene laherparepvecTTI-621 will be given in combination with talimogene laherparepvec (T-Vec). Subjects in this cohort must have unresectable melanoma. | Other | TTI-621 + T-Vec |
| TTI-621 + radiationAlso: SIRPα-IgG1 Fc + radiationTTI-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 | TTI-621 + Radiation |
Primary outcome
Optimal TTI-621 delivery regimen
Time frame: 10 months
Defining the optimal TTI-621 delivery regimen in subjects with advanced percutaneously-accessible cancer
2 secondary outcomes
Frequency and severity of adverse events
Time frame: 15 months
Preliminary evidence of anti-tumor activity of TTI-621
Time frame: 15 months
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2023.
- Derived from this study: PubMed 34627593Querfeld 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.
- Derived from this study: PubMed 34519839Kruglov 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TTI-621 Monotherapy, TTI-621 + PD-1/PD-L1 Inhibitor and TTI-621 + pegylated interferon-α2a in people with Solid Tumors and Mycosis Fungoides, run by Pfizer at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Optimal TTI-621 delivery regimen (time frame: 10 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02890368, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2023.