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

NCT02663518 | Terminated Phase 1 Results

• 2 other identifiers: TTI-621-01C4961001
• Study Type: interventional
• Target: 249
• Locations: 2 countries
• Sites: 51

Brief Summary

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

Conditions

Hematologic Malignancies; Solid Tumor

Keywords

PF-07901800; ABCL; Aggressive B-cell lymphoma; CLL; Chronic lymphocytic leukemia; CTCL; Cutaneous T-Cell Lymphoma; HL; Hodgkin lymphoma; IBCL; Indolent B-cell lymphoma; MDS; Myelodysplastic syndromes; MPN; Myeloproliferative neoplasms; MM; Multiple Myeloma; PTCL; Peripheral T-cell lymphomas; SCLC; Small Cell Lung Cancer; T-cell lymphoma; Rituximab; Nivolumab; TTI-621; Solid Tumor; Hematologic Malignancies; Lymphoma; CD47; SIRPα-IgG1 Fc

Outcome Measures

Primary Outcomes (5)

• Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

  An adverse event (AE) was any untoward medical occurrence in administered medicinal product, event need not necessarily have a causal relationship with product treatment or usage. A serious adverse event (SAE) was any untoward medical occurrence in a participant administered a medicinal or nutritional product (including pediatric formulas) at any dose that: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect. Treatment emergent AEs were events emerged during treatment period and were absent before treatment or that worsened relative to pretreatment state.

  Part 1: Day 1 of dosing up to 30 days of safety follow-up visit after the last dose (maximum treatment exposure for Part 1 was 414 days)

• Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)

  DLT was defined as any of the protocol specified TEAEs that occurred during the 21-day. DLT treatment/observation period (including the pre-dose tests on Day 22/Week 4 Day 1) and that were considered at least possibly related to study treatment by the investigator. Protocol specified DLT TEAE criteria: Grade 4 thrombocytopenia; Grade 3 thrombocytopenia with bleeding (with the exception of brief, easily-controlled epistaxis, mild gum bleeding or normal menses) or with any requirement for platelet transfusions; Grade 4 anemia, unexplained by underlying disease; Grade 4 neutropenia lasting more than 5 days; Febrile neutropenia of any duration ( Absolute Neutrophil Count (ANC) less than (\<) 1.0 \* 10\^9/L. fever greater than (\>) 38.5° Degree Celsius (C); Grade 3 or higher non-hematologic toxicity except for alopecia and nausea controlled by medical management; Grade 3 or 4 hemorrhage.

  Part 1: Day 1 of dosing up to Pre-dose on Day 22

• Part 2 and 3: Number of Participants With TEAEs and TESAEs

  An AE was any untoward medical occurrence in administered medicinal product, event need not necessarily have a causal relationship with product treatment or usage. A SAE was any untoward medical occurrence in a participant administered a medicinal or nutritional product (including pediatric formulas) at any dose that: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect. Treatment emergent AEs were events emerged during treatment period and were absent before treatment or that worsened relative to pretreatment state.

  Day 1 of dosing up to 30 days of safety follow-up visit after the last dose (maximum treatment exposure for Part 2 was 1793 days and for Part 3 was 938 days)

• Part 4: Number of Participants With TEAEs and TESAEs

  An AE was any untoward medical occurrence in administered medicinal product, event need not necessarily have a causal relationship with product treatment or usage. A SAE event was any untoward medical occurrence in a participant administered a medicinal or nutritional product (including pediatric formulas) at any dose that: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect. Treatment emergent AEs were events emerged during treatment period and were absent before treatment or that worsened relative to pretreatment state.

  Part 4: Day 1 of dosing up to 1 year of safety follow-up visit after the last dose (maximum treatment exposure for Part 4 was 667 days)

• Part 4: Number of Participants With Dose Limiting Toxicities (DLTs)

  DLT was defined as any of the protocol specified TEAEs that occurred during the 21-day. DLT treatment/observation period (including the pre-dose tests on Day 22/Week 4 Day 1) and that were considered at least possibly related to study treatment by the investigator. Protocol specified DLT TEAE criteria: Grade 4 thrombocytopenia; Grade 3 thrombocytopenia with bleeding (with the exception of brief, easily-controlled epistaxis, mild gum bleeding or normal menses) or with any requirement for platelet transfusions; Grade 4 anemia, unexplained by underlying disease; Grade 4 neutropenia lasting more than 5 days; Febrile neutropenia of any duration (ANC \< 1.0 x 109/L, fever \> 38.5°C); Grade 3 or higher non-hematologic toxicity except for alopecia and nausea controlled by medical management; Grade 3 or 4 hemorrhage.

  Part 4: Day 1 of dosing up to Pre-dose on Day 22

Secondary Outcomes (24)

• Part 1: Maximum Plasma Concentration (Cmax) of TTI-621

  Part 1: Pre-dose, end of infusion (EOI), 2, 4, 24, 72, 168 hours post dose on Week 1

• Part 1: Area Under the Plasma Concentration Time Curve From Time Zero to 168 (AUC[0-168]) of TTI-621

  Part 1: Pre-dose, end of infusion (EOI), 2, 4, 24, 72, 168 hours post dose on Week 1

• Part 1: Percentage of CD47 Receptor Occupancy on Peripheral Blood CD3+ Cells

  Part 1: Week 1 end of infusion (EOI)

• Part 1: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb)

  Part 1: From pre-infusion on day 1 up to end of study treatment (maximum treatment exposure for Part 1 was 414 days)

• Part 2 and 3 Combined: Maximum Plasma Concentration (Cmax) of TTI-621

  Part 2 and 3: Pre-dose, end of infusion (EOI), 2, 4, 24, 72, 168 hours post dose on Week 1

Study Arms (16)

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

EXPERIMENTAL

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

Drug: PF-0791800 (TTI-621)

Indolent B-Cell Lymphoma

EXPERIMENTAL

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

Drug: PF-0791800 (TTI-621)

Aggressive B-Cell Lymphoma

EXPERIMENTAL

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

Drug: PF-0791800 (TTI-621)

T-Cell Lymphoma

EXPERIMENTAL

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

Drug: PF-0791800 (TTI-621)

Hodgkin Lymphoma

EXPERIMENTAL

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

Drug: PF-0791800 (TTI-621)

Chronic Lymphocytic Leukemia

EXPERIMENTAL

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

Drug: PF-0791800 (TTI-621)

Multiple Myeloma

EXPERIMENTAL

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

Drug: PF-0791800 (TTI-621)

Acute Myeloid Leukemia

EXPERIMENTAL

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

Drug: PF-0791800 (TTI-621)

Myelodysplastic Syndrome

EXPERIMENTAL

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

Drug: PF-0791800 (TTI-621)

Myeloproliferative Neoplasms

EXPERIMENTAL

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

Drug: PF-0791800 (TTI-621)

Small Cell Lung Cancer

EXPERIMENTAL

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

Drug: PF-0791800 (TTI-621)

Rituximab Combination

EXPERIMENTAL

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

Drug: PF-07901800 (TTI-621) plus Rituximab

Nivolumab Combination

EXPERIMENTAL

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

Drug: PF-07901800 (TTI-621) plus Nivolumab

Cutaneous T-Cell Lymphoma (CTCL)

EXPERIMENTAL

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

Drug: PF-0791800 (TTI-621)

Peripheral T-Cell Lymphoma (PTCL)

EXPERIMENTAL

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

Drug: PF-0791800 (TTI-621)

Part 4: Cutaneous T-Cell Lymphoma (CTCL)

EXPERIMENTAL

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

Drug: PF-0791800 (TTI-621)

Interventions

PF-0791800 (TTI-621) DRUG

Monotherapy

Also known as: TTI-621 (SIRPα-IgG1 Fc)

Acute Myeloid Leukemia; Aggressive B-Cell Lymphoma; Chronic Lymphocytic Leukemia; Cutaneous T-Cell Lymphoma (CTCL); Hodgkin Lymphoma; Indolent B-Cell Lymphoma; Multiple Myeloma; Myelodysplastic Syndrome; Myeloproliferative Neoplasms; PF-07901800 (TTI-621) Escalation Phase - R/R Lymphoma; Part 4: Cutaneous T-Cell Lymphoma (CTCL); Peripheral T-Cell Lymphoma (PTCL); Small Cell Lung Cancer; T-Cell Lymphoma

PF-07901800 (TTI-621) plus Rituximab DRUG

Combination therapy

Also known as: TTI-621 plus Rituxan

Rituximab Combination

PF-07901800 (TTI-621) plus Nivolumab DRUG

Combination therapy

Also known as: TTI-621 plus Opdivo

Nivolumab Combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (51)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Freidenrich Center for Translational Research (CTRU)

Palo Alto, California, 94304, United States

Location

Stanford Cancer Institute

Palo Alto, California, 94304, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Presbyterian/St.Luke's Medical Center

Denver, Colorado, 80218, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

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

Tampa, Florida, 33612, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Covance Biorepository

Greenfield, Indiana, 46140, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Hackensack Meridian Health John Theurer Cancer Center

Hackensack, New Jersey, 07601, United States

Location

Hackensack UMC

Hackensack, New Jersey, 07601, United States

Location

The John Theurer Cancer Center at Hackensack UMC

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan Kettering Cancer Center- Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Cancer Center Westchester

Harrison, New York, 10604, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, 10016, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

NYU Investigational Pharmacy

New York, New York, 10016, United States

Location

NYU Langone Health (Tisch Hospital)

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Cancer Center-Clinical Trails Office

New York, New York, 10017, United States

Location

Columbia Univeristy

New York, New York, 10019, United States

Location

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

New York, New York, 10021, United States

Location

Memorial Sloan Kettering Cancer Center Rockefeller Outpatient Pavillion

New York, New York, 10022, United States

Location

Columbia University Medical Center.

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Oregon Health & Science University-Research Pharmacy Services

Portland, Oregon, 97239, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Oregon Health and Sciences University

Portland, Oregon, 97239, United States

Location

University of Pittsburgh Medical Center Presbyterian Shadyside

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15237, United States

Location

Centennial Medical Center

Nashville, Tennessee, 37203, United States

Location

Sarah Cannon Research Institute (Pharmacy)

Nashville, Tennessee, 37203, United States

Location

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Myriad RMB Inc

Austin, Texas, 78759, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Texas MD Anderson Cancer Center, Cancer Prevention Center

Houston, Texas, 77030, United States

Location

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

Houston, Texas, 77030, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

University of Washington - Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Fairmont Medical Building, Suite 810

Vancouver, B.C., V5Z1H7, Canada

Location

British Columbia Cancer Agency

Vancouver, British Columbia, V5Z 1H6, Canada

Location

Princess Margaret Cancer Center

Toronto, Ontario, M5G 2M9, Canada

Location

University Health Network - Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (3)

• 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.

  PMID: 36841672 DERIVED

• 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.

  PMID: 33451977 DERIVED

• 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.

  PMID: 30962222 DERIVED

Related Links

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

MeSH Terms

Conditions

Hematologic Neoplasms; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, T-Cell, Cutaneous; Hodgkin Disease; Myelodysplastic Syndromes; Myeloproliferative Disorders; Multiple Myeloma; Lymphoma, T-Cell, Peripheral; Small Cell Lung Carcinoma; Lymphoma, T-Cell; Lymphoma

Interventions

TTI-621; Rituximab; Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Bone Marrow Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Humanized

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open label
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 19, 2016
• First Posted: January 26, 2016
• Study Start: January 28, 2016
• Primary Completion: November 23, 2022
• Study Completion: November 23, 2022
• Last Updated: May 10, 2024
• Results First Posted: May 10, 2024

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (47); CA (4)