A Trial of PF-07901800 (TTI-621) for Patients With Hematologic Malignancies and Selected Solid Tumors

NCT ID: NCT02663518

Last Updated: 2024-05-10

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

249 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-28

Study Completion Date

2022-11-23

Brief Summary

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Multicenter, open-label, phase 1a/1b trial of PF-07901800 (TTI-621) in subjects with relapsed or refractory hematologic malignancies and selected solid tumors.

Detailed Description

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This is a trial of PF-07901800 (TTI-621) in subjects with relapsed or refractory hematologic malignancies and selected solid tumors.

TTI-621 (SIRPαFc) 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" (anti phagocytic) signal to macrophages.

This trial will be conducted in 2 phases and 4 parts: Phase 1a Part 1 (escalation phase) and Phase 1b Parts 2-4 (expansion phase).

In the dose Escalation Phase (phase 1a Part 1), subjects with lymphoma will be enrolled in sequential dose cohorts to receive TTI-621 to characterize safety, tolerability, pharmacokinetics, and the maximum-tolerated dose (MTD).

In the Expansion Phase (phase 1b Parts 2-4), TTI-621 will be given to subjects with a variety of hematologic malignancies and selected solid tumors to further define safety and to characterize efficacy. In the Expansion Phase Part 2, the safety and efficacy of TTI-621 will also be assessed when it is given in combination with other anti-cancer drugs. The dose of TTI-621 to be delivered in the Expansion Phase Parts 2-3 of the study may be increased or decreased based on the subject's tolerability and on the subject's response to treatment.

In the phase 1b dose optimization of the study (Part 4), further dose escalation of TTI-621, beyond the dose determined during phase 1a dose escalation, will be pursued in patients with relapsed and/or refractory CTCL following a 3+3 escalation design and using a revised DLT criteria to further evaluate the safety and tolerability of TTI-621 at dose levels higher than the initially recommended phase 1b Parts 2-3.

Secondary objectives include further characterization of the pharmacokinetics, pharmacodynamics, and development of ADA; and to gain preliminary evidence of the anti-tumor activity of TTI-621 in subjects with a variety of hematologic malignancies and selected solid tumors. In addition, the safety of TTI-621 will be evaluated in combination with other anti-cancer agents.

Pfizer decided terminating this study for administrative reasons on 22Mar2022 (stopping enrollment as of 15Apr2022). The decision wasn't due to safety concerns or requests from regulatory authorities.

Conditions

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Hematologic Malignancies Solid Tumor

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Phase 1a/1b trial of PF-07901800 (TTI-621) for relapsed or refractory hematologic malignancies and selected solid tumors were conducted in 4 parts. In the dose escalation phase (Part 1), advanced lymphomas were enrolled in sequential dose cohorts for safety, tolerability, PK, and MTD. In the expansion phase (Part 2), subjects with various hematologic malignancies and selected solid tumors were treated at recommended dose determined in phase 1a (Part 1) for safety and efficacy. In the expansion phase (Part 3), 2 cohorts (cutaneous T-cell lymphoma and peripheral T-cell lymphoma) were evaluated for potentially further studied using Simon 2-stage design. In the phase 1b dose optimization (Part 4), further dose escalation was investigated in patients with relapsed and/or refractory CTCL following a 3+3 escalation and revised DLT criteria.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Open label

Study Groups

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PF-07901800 (TTI-621) Escalation Phase - R/R Lymphoma

The Escalation Phase will include multiple doses of PF-07901800 (TTI-621)

Group Type EXPERIMENTAL

PF-0791800 (TTI-621)

Intervention Type DRUG

Monotherapy

Indolent B-Cell Lymphoma

Monotherapy expansion cohort with PF-07901800 (TTI-621)

Group Type EXPERIMENTAL

PF-0791800 (TTI-621)

Intervention Type DRUG

Monotherapy

Aggressive B-Cell Lymphoma

Monotherapy expansion cohort with PF-07901800 (TTI-621)

Group Type EXPERIMENTAL

PF-0791800 (TTI-621)

Intervention Type DRUG

Monotherapy

T-Cell Lymphoma

Monotherapy expansion cohort with PF-07901800 (TTI-621)

Group Type EXPERIMENTAL

PF-0791800 (TTI-621)

Intervention Type DRUG

Monotherapy

Hodgkin Lymphoma

Monotherapy expansion cohort with PF-07901800 (TTI-621)

Group Type EXPERIMENTAL

PF-0791800 (TTI-621)

Intervention Type DRUG

Monotherapy

Chronic Lymphocytic Leukemia

Monotherapy expansion cohort with PF-07901800 (TTI-621)

Group Type EXPERIMENTAL

PF-0791800 (TTI-621)

Intervention Type DRUG

Monotherapy

Multiple Myeloma

Monotherapy expansion cohort with PF-07901800 (TTI-621)

Group Type EXPERIMENTAL

PF-0791800 (TTI-621)

Intervention Type DRUG

Monotherapy

Acute Myeloid Leukemia

Monotherapy expansion cohort with PF-07901800 (TTI-621)

Group Type EXPERIMENTAL

PF-0791800 (TTI-621)

Intervention Type DRUG

Monotherapy

Myelodysplastic Syndrome

Monotherapy expansion cohort with PF-07901800 (TTI-621)

Group Type EXPERIMENTAL

PF-0791800 (TTI-621)

Intervention Type DRUG

Monotherapy

Myeloproliferative Neoplasms

Monotherapy expansion cohort with PF-07901800 (TTI-621)

Group Type EXPERIMENTAL

PF-0791800 (TTI-621)

Intervention Type DRUG

Monotherapy

Small Cell Lung Cancer

Monotherapy expansion cohort with PF-07901800 (TTI-621)

Group Type EXPERIMENTAL

PF-0791800 (TTI-621)

Intervention Type DRUG

Monotherapy

Rituximab Combination

Combination therapy expansion cohort with PF-07901800 (TTI-621) plus Rituximab for CD20 positive malignancies

Group Type EXPERIMENTAL

PF-07901800 (TTI-621) plus Rituximab

Intervention Type DRUG

Combination therapy

Nivolumab Combination

Combination therapy expansion cohort with PF-07901800 (TTI-621) plus Nivolumab for Hodgkin Lymphoma

Group Type EXPERIMENTAL

PF-07901800 (TTI-621) plus Nivolumab

Intervention Type DRUG

Combination therapy

Cutaneous T-Cell Lymphoma (CTCL)

Monotherapy expansion cohort with PF-07901800 (TTI-621)

Group Type EXPERIMENTAL

PF-0791800 (TTI-621)

Intervention Type DRUG

Monotherapy

Peripheral T-Cell Lymphoma (PTCL)

Monotherapy expansion cohort with PF-07901800 (TTI-621)

Group Type EXPERIMENTAL

PF-0791800 (TTI-621)

Intervention Type DRUG

Monotherapy

Part 4: Cutaneous T-Cell Lymphoma (CTCL)

Monotherapy expansion Part 4 (Dose Optimization) cohort with PF-07901800 (TTI-621)

Group Type EXPERIMENTAL

PF-0791800 (TTI-621)

Intervention Type DRUG

Monotherapy

Interventions

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PF-0791800 (TTI-621)

Monotherapy

Intervention Type DRUG

PF-07901800 (TTI-621) plus Rituximab

Combination therapy

Intervention Type DRUG

PF-07901800 (TTI-621) plus Nivolumab

Combination therapy

Intervention Type DRUG

Other Intervention Names

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TTI-621 (SIRPα-IgG1 Fc) TTI-621 plus Rituxan TTI-621 plus Opdivo

Eligibility Criteria

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Inclusion Criteria

* Advanced measurable malignancy with previously progressed on, or currently progressing on standard anticancer therapy or for whom no other approved conventional therapy exists
* Eastern Cooperative Oncology Group (ECOG) 0-2
* Adequate hematologic, hepatic, renal, and coagulation function; fresh or archived tumor tissue available for immunohistochemistry
* Recovery from prior treatments and/or surgeries; no history of hemolytic anemia or bleeding diathesis.
* AML M3 (French American British, FAB, classification) (i.e., acute promyelocytic leukemia \[APL\]) excluded

Exclusion Criteria

* Known current central nervous system disease involvement or untreated brain metastases
* Allogeneic transplant within 30 days prior to the planned start of treatment or subjects with active graft-vs-host disease with the exception of Grade 1 skin involvement
* History of hemolytic anemia or bleeding diathesis
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

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City of Hope National Medical Center

Duarte, California, United States

Site Status

City of Hope

Duarte, California, United States

Site Status

Freidenrich Center for Translational Research (CTRU)

Palo Alto, California, United States

Site Status

Stanford Cancer Institute

Palo Alto, California, United States

Site Status

Colorado Blood Cancer Institute

Denver, Colorado, United States

Site Status

Presbyterian/St.Luke's Medical Center

Denver, Colorado, United States

Site Status

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

Site Status

Mayo Clinic

Jacksonville, Florida, United States

Site Status

Moffitt Cancer Center Richard M Schulze Family Foundation Outpatient Center at McKinley Campus

Tampa, Florida, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Covance Biorepository

Greenfield, Indiana, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Hackensack Meridian Health John Theurer Cancer Center

Hackensack, New Jersey, United States

Site Status

Hackensack UMC

Hackensack, New Jersey, United States

Site Status

The John Theurer Cancer Center at Hackensack UMC

Hackensack, New Jersey, United States

Site Status

Memorial Sloan Kettering Cancer Center- Monmouth

Middletown, New Jersey, United States

Site Status

Memorial Sloan Kettering Cancer Center Westchester

Harrison, New York, United States

Site Status

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, United States

Site Status

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, United States

Site Status

NYU Investigational Pharmacy

New York, New York, United States

Site Status

NYU Langone Health (Tisch Hospital)

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center-Clinical Trails Office

New York, New York, United States

Site Status

Columbia Univeristy

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center - David H. Koch Center for Cancer Care

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center Rockefeller Outpatient Pavillion

New York, New York, United States

Site Status

Columbia University Medical Center.

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Oregon Health & Science University-Research Pharmacy Services

Portland, Oregon, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

Oregon Health and Sciences University

Portland, Oregon, United States

Site Status

University of Pittsburgh Medical Center Presbyterian Shadyside

Pittsburgh, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Centennial Medical Center

Nashville, Tennessee, United States

Site Status

Sarah Cannon Research Institute (Pharmacy)

Nashville, Tennessee, United States

Site Status

Tennessee Oncology PLLC

Nashville, Tennessee, United States

Site Status

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Site Status

Tennessee Oncology

Nashville, Tennessee, United States

Site Status

Myriad RMB Inc

Austin, Texas, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

University of Texas MD Anderson Cancer Center, Cancer Prevention Center

Houston, Texas, United States

Site Status

University of Texas MD Anderson Cancer Center, Melanoma and Skin Clinic

Houston, Texas, United States

Site Status

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

University of Washington - Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

Fairmont Medical Building, Suite 810

Vancouver, B.C., Canada

Site Status

British Columbia Cancer Agency

Vancouver, British Columbia, Canada

Site Status

Princess Margaret Cancer Center

Toronto, Ontario, Canada

Site Status

University Health Network - Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

References

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Marks JA, Wang X, Fenu EM, Bagg A, Lai C. TP53 in AML and MDS: The new (old) kid on the block. Blood Rev. 2023 Jul;60:101055. doi: 10.1016/j.blre.2023.101055. Epub 2023 Feb 14.

Reference Type DERIVED
PMID: 36841672 (View on PubMed)

Ansell SM, Maris MB, Lesokhin AM, Chen RW, Flinn IW, Sawas A, Minden MD, Villa D, Percival MM, Advani AS, Foran JM, Horwitz SM, Mei MG, Zain J, Savage KJ, Querfeld C, Akilov OE, Johnson LDS, Catalano T, Petrova PS, Uger RA, Sievers EL, Milea A, Roberge K, Shou Y, O'Connor OA. Phase I Study of the CD47 Blocker TTI-621 in Patients with Relapsed or Refractory Hematologic Malignancies. Clin Cancer Res. 2021 Apr 15;27(8):2190-2199. doi: 10.1158/1078-0432.CCR-20-3706. Epub 2021 Jan 15.

Reference Type DERIVED
PMID: 33451977 (View on PubMed)

Johnson LDS, Banerjee S, Kruglov O, Viller NN, Horwitz SM, Lesokhin A, Zain J, Querfeld C, Chen R, Okada C, Sawas A, O'Connor OA, Sievers EL, Shou Y, Uger RA, Wong M, Akilov OE. Targeting CD47 in Sezary syndrome with SIRPalphaFc. Blood Adv. 2019 Apr 9;3(7):1145-1153. doi: 10.1182/bloodadvances.2018030577.

Reference Type DERIVED
PMID: 30962222 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://pmiform.com/clinical-trial-info-request?StudyID=TTI-621-01

To obtain contact information for a study center near you, click here.

Other Identifiers

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C4961001

Identifier Type: OTHER

Identifier Source: secondary_id

TTI-621-01

Identifier Type: -

Identifier Source: org_study_id

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