Clinical trial NCT02890368: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: 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
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2016-09-07
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Optimal TTI-621 delivery regimen
timeFrame: 10 months
Secondary outcomes:
measure: Frequency and severity of adverse events
timeFrame: 15 months
measure: Preliminary evidence of anti-tumor activity of TTI-621
timeFrame: 15 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center at NYU Langone Health
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Seattle
country: United States
facility: University of Washington - Seattle Cancer Care Alliance
state: Washington
Study officials:
References:
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.
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.