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

Melanoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02890368
• Other study ID #: TTI-621-02
• Status: Terminated
• Phase: Phase 1
• Start date: September 2016
• Est. completion date: March 31, 2020

Study information

• Verified date: March 2023
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 56
• Est. completion date: March 31, 2020
• Est. primary completion date: March 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• TTI-621 Monotherapy
TTI-621 (SIRPa-IgG1 Fc) is a soluble recombinant fusion protein created by directly linking the sequences encoding the N-terminal CD47 binding domain of human SIRPa 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 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-a2a
TTI-621 will be given in combination with pegylated interferon-a2a. Subjects in this cohort must have a cancer diagnosis for which pegylated interferon-a2a is approved by the FDA or listed in the National Comprehensive Cancer Network (NCCN) Guidelines.

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.
• 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).

Locations

Country	Name	City	State
United States	City of Hope National Medical Center	Duarte	California
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone Health	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	University of Washington - Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Optimal TTI-621 delivery regimen	Defining the optimal TTI-621 delivery regimen in subjects with advanced percutaneously-accessible cancer	10 months
Secondary	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
Secondary	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