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

Sponsor

Trillium Therapeutics Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT02890368

Collaborator

(none)

Enrollment

Locations

Arms

42.9

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors Mycosis Fungoides Melanoma Merkel-cell Carcinoma Squamous Cell Carcinoma Breast Carcinoma Human Papillomavirus-Related Malignant Neoplasm Soft Tissue Sarcoma	Drug: TTI-621 Monotherapy Drug: TTI-621 + PD-1/PD-L1 Inhibitor Drug: TTI-621 + pegylated interferon-α2a Other: TTI-621 + T-Vec Other: TTI-621 + radiation	Phase 1

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

Study Type:

Interventional

Actual Enrollment :

56 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Sep 1, 2016

Actual Primary Completion Date :

Mar 31, 2020

Actual Study Completion Date :

Mar 31, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Optimal TTI-621 delivery regimen [10 months]
Defining the optimal TTI-621 delivery regimen in subjects with advanced percutaneously-accessible cancer

Secondary Outcome Measures

Frequency and severity of adverse events [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
Preliminary evidence of anti-tumor activity of TTI-621 [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope National Medical Center	Duarte	California	United States	91010
2	Laura and Isaac Perlmutter Cancer Center at NYU Langone Health	New York	New York	United States	10016
3	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
4	Oregon Health & Science University	Portland	Oregon	United States	97239
5	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15237
6	Inova Schar Cancer Institute	Fairfax	Virginia	United States	22031
7	University of Washington - Seattle Cancer Care Alliance	Seattle	Washington	United States	98109