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

Phase 1

Terminated

• Conditions: Melanoma; Merkel-cell Carcinoma; Breast Carcinoma; Squamous Cell Carcinoma; Solid Tumors; Mycosis Fungoides; Human Papillomavirus-Related Malignant Neoplasm; Soft Tissue Sarcoma
• Interventions: Other: TTI-621 + T-Vec; Drug: TTI-621 Monotherapy; Other: TTI-621 + radiation; Drug: TTI-621 + PD-1/PD-L1 Inhibitor; Drug: TTI-621 + pegylated interferon-α2a

• Registration Number: NCT02890368
• Lead Sponsor: Pfizer

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.

Study Timeline

• Study First Submitted: 2016-08-26
• Study First Submitted QC: 2016-08-31
• Study Start: 2016-09
• Study First Posted: 2016-09-07
• Primary Completion: 2020-03-31
• Study Completion: 2020-03-31
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-31
• Last Update Posted: 2023-04-05

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 56

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TTI-621 + T-Vec	TTI-621 + T-Vec	Combination Therapy Expansion Cohort of TTI-621 plus T-Vec
TTI-621 Monotherapy Escalation	TTI-621 Monotherapy	TTI-621 Escalation phase of single or multiple doses of TTI-621 delivered by intratumoral injections (various dose cohorts).
TTI-621 + Radiation	TTI-621 + radiation	Combination Therapy Expansion Cohort of TTI-621 plus Radiation Therapy
TTI-621 Monotherapy (Single Lesion)	TTI-621 Monotherapy	TTI-621 Single Lesion Injection Expansion Cohort
TTI-621 Monotherapy (Multiple Lesions)	TTI-621 Monotherapy	TTI-621 Multiple Lesion Injections Expansion Cohort
TTI-621 + PD-1/PD-L1 Inhibitor	TTI-621 + PD-1/PD-L1 Inhibitor	Combination Therapy Expansion Cohort of TTI-621 plus PD-1/PD-L1 Inhibitor
TTI-621 + Pegylated Interferon-α2a	TTI-621 + pegylated interferon-α2a	Combination Therapy Expansion Cohort of TTI-621 plus Pegylated Interferon-α2a

Primary Outcome Measures

Name	Time	Method
Optimal TTI-621 delivery regimen	10 months	Defining the optimal TTI-621 delivery regimen in subjects with advanced percutaneously-accessible cancer

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (7)

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Washington - Seattle Cancer Care Alliance; 🇺🇸 Seattle, Washington, United States

City of Hope National Medical Center; 🇺🇸 Duarte, California, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health; 🇺🇸 New York, New York, United States

Inova Schar Cancer Institute; 🇺🇸 Fairfax, Virginia, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States