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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Solid Tumors, Mycosis Fungoides, Melanoma, Merkel-cell Carcinoma, Squamous Cell Carcinoma, Breast Carcinoma, Human Papillomavirus-Related Malignant Neoplasm, Soft Tissue Sarcoma

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TTI-621 Monotherapy Escalation<br>TTI-621 Escalation phase of single or multiple doses of TTI-621 delivered by intratumoral injections (various dose cohorts). | Drug: TTI-621 Monotherapy<br>* 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.<br>* Other names: SIRPα-IgG1 Fc;|
| Experimental: TTI-621 Monotherapy (Single Lesion)<br>TTI-621 Single Lesion Injection Expansion Cohort | Drug: TTI-621 Monotherapy<br>* 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.<br>* Other names: SIRPα-IgG1 Fc;|
| Experimental: TTI-621 Monotherapy (Multiple Lesions)<br>TTI-621 Multiple Lesion Injections Expansion Cohort | Drug: TTI-621 Monotherapy<br>* 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.<br>* Other names: SIRPα-IgG1 Fc;|
| Experimental: TTI-621 + PD-1/PD-L1 Inhibitor<br>Combination Therapy Expansion Cohort of TTI-621 plus PD-1/PD-L1 Inhibitor | Drug: TTI-621 + PD-1/PD-L1 Inhibitor<br>* 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.<br>* Other names: SIRPα-IgG1 Fc + PD-1/PD-L1 Inhibitor;|
| Experimental: TTI-621 + Pegylated Interferon-α2a<br>Combination Therapy Expansion Cohort of TTI-621 plus Pegylated Interferon-α2a | Drug: TTI-621 + pegylated interferon-α2a<br>* 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.<br>* Other names: SIRPα-IgG1 Fc + pegylated interferon-α2a;|
| Experimental: TTI-621 + T-Vec<br>Combination Therapy Expansion Cohort of TTI-621 plus T-Vec | Other: TTI-621 + T-Vec<br>* TTI-621 will be given in combination with talimogene laherparepvec (T-Vec). Subjects in this cohort must have unresectable melanoma.<br>* Other names: SIRPα-IgG1 Fc + talimogene laherparepvec;|
| Experimental: TTI-621 + Radiation<br>Combination Therapy Expansion Cohort of TTI-621 plus Radiation Therapy | Other: TTI-621 + radiation<br>* 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).<br>* Other names: SIRPα-IgG1 Fc + radiation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optimal TTI-621 delivery regimen | Defining the optimal TTI-621 delivery regimen in subjects with advanced percutaneously-accessible cancer | 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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 | 15 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD47, SIRPa, Immunotherapy, Checkpoint inhibitor