A Clinical Trial to Learn About the Study Medicine Called Maplirpacept (PF-07901801), Alone and When Used in Combination With Other Medicines to Treat Participants With Advanced Hematological Malignancies, Including Lymphoma, Leukemia and Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

A Phase 1a/1b Dose-Escalation and Expansion Trial of TTI-622 in Patients With Advanced Hematologic Malignancies, Including Lymphoma, Leukemia, and Multiple Myeloma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03530683
• Other study ID #: TTI-622-01
• Secondary ID: C4971001
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: June 7, 2018
• Est. completion date: September 11, 2024

Study information

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

Clinical Trial Summary

The purpose of this clinical trial is to learn how the experimental medicine maplirpacept (PF-07901801) affects people with various types of blood cancers:

• relapsed or refractory (R/R) lymphoma

• multiple myeloma

• newly diagnosed acute myeloid leukemia (AML).

This trial will be conducted in the outpatient setting in 2 parts, phase 1a and phase 1b. You may only participate in one part of the study.

During phase 1a of this study, we will explore how much maplirpacept (PF-07901801), when used by itself, can be safely used.

If you have lymphoma, the study medicine maplirpacept (PF-07901801) will be given by infusion through a vein once a week or once every 2 weeks or every 3 weeks as determined by your doctor. Following your first dose, you will be expected to come back twice more the first week. From week 2, you will have weekly visits for blood tests, questions about your medications, any side effects, or illnesses you may have experienced and your cancer response. After you have completed 21 days (for every week dosing) or 42 days (for every 2- or 3-weeks dosing), your doctor will discuss whether you should stop study treatment or continue.

If you continue, you will be expected to come back weekly for blood tests, vital signs, a brief physical exam, asked about any side effects or illnesses you may have experienced and medications you may be taking. The dosing schedule you are assigned to will continue until your disease has worsened, significant side effects occur or other reasons that lead you and your doctor to decide treatment may be stopped.

To be eligible for the first part of the study you must be 18 years or older, your disease has worsened after receiving other medicines approved for blood cancer, no other treatment options exist for you, a sample of your tissue for exploratory research which can be taken from tissue already obtained or if necessary, a new sample of your tissue will be taken so your disease may be seen and measured on routine tests/scans. If you have had radiation therapy or received any anticancer medication within 14 days before the planned start of study treatment your doctor will let you know if you are eligible to participate in the study. If you have had major surgery within 30 days before the planned start of study treatment you may not be eligible to participate.

The phase 1a part of the study may last up to 51/2 years. How long you participate in this study depends on side effects you may have to the study drug. It also depends on how your cancer responds to the study drug. Therefore, you may remain in the study as long as you and your study doctor think you may benefit. However, you are free to stop taking part in this study at any time and for any reason.

During phase 1b part of this study, we will explore how much maplirpacept (PF-07901801), when used with other anticancer medicine(s), can be safe and reduce cancer growth. In the phase 1b part of this study, you will receive maplirpacept (PF-07901801) and other anticancer medicine(s). Which medicine combination you will receive depends on the types of cancer under treatment. Your treatment experiences will be examined to determine if maplirpacept (PF-07901801) when given with other anticancer medicine(s), is safe and can reduce cancer growth.

To be eligible for the second part of the study you may have newly diagnosed Acute Myelocytic Leukemia with or without a genetic mutation or you have Multiple Myeloma or Diffuse Large B Cell Lymphoma, and your disease has worsened.

The Phase 1b part of this study may last as long as you and your study doctor think you may benefit which could be up to approximately 31/2 years. How long you participate in this study depends on side effects you may have to the study drug. It also depends on how your cancer responds to the study drug. Therefore, you may remain in the study as long as you and your study doctor think you may benefit. However, you are free to stop taking part in this study at any time and for any reason.

Description:

This is a trial of maplirpacept (PF-07901801) in subjects with relapsed or refractory lymphoma or multiple myeloma (MM) and subjects with newly diagnosed acute myeloid leukemia (AML).

This trial will be conducted in 2 phases: Phase 1a (Dose-Escalation Phase for Single-Agent maplirpacept (PF-07901801) and Phase 1b maplirpacept (PF-07901801) Combinations and Single-Agent.

In the Dose-Escalation Phase for Single-Agent maplirpacept (PF-07901801), subjects with relapsed or refractory lymphoma will be enrolled in sequential dose cohorts.

In the Combination and Single-Agent Treatment part, subjects will be included in 1 of 14 cohorts: (Cohort A1 and A2) subjects with newly diagnosed TP53-mutated AML will be treated with maplirpacept (PF-07901801) + azacitidine; (Cohort B1 and B2) elderly subjects or subjects unfit for intensive induction chemotherapies with newly diagnosed TP53-wildtype AML will be treated with maplirpacept (PF-07901801) + azacitidine and venetoclax; (Cohort C1, C2, and C3) subjects with relapsed or refractory MM will be treated with maplirpacept (PF-07901801) + carfilzomib and dexamethasone;(Cohort D1 and D2) subjects in relapsed or refractory CD20+ diffuse large B-cell lymphoma will be treated with maplirpacept (PF-07901801) + an anti-CD20 targeting agent; (Cohort E1 and E2) subjects with relapsed refractory MM will be treated with single-agent maplirpacept (PF-07901801); and (Cohorts F1, F2 and F3) with relapsing or refractory MM will be treated with increasing doses of maplirpacept (PF-07901801) + isatuximab, carfilzomib and dexamethasone.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 177
• Est. completion date: September 11, 2024
• Est. primary completion date: September 11, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria (Phase 1a and Phase 1b, all Cohorts):

1. Available fresh or archived tumor tissue.

2. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.

3. Adequate coagulation function.

4. Adequate hepatic function.

5. Adequate hematologic status.

6. Adequate renal function.

7. Recovery from non-hematopoietic toxicities of previous anticancer drugs or radiotherapy or previous surgeries to =Grade 1 (or to baseline grade if condition was pre-existing).

Key Inclusion Criteria (Phase 1a): Histologically confirmed relapsed/refractory, transfusion- independent lymphoma (Hodgkin or non-Hodgkin) per the 2014 Lugano classification.

Key Inclusion Criteria (Phase 1b Cohort A1 and A2): Histologically confirmed, newly diagnosed TP53-mutated Acute Myeloid Leukemia (AML).

Key Inclusion Criteria (Phase 1b Cohort B1 and B2): Histologically confirmed, newly diagnosed TP53-wildtype AML, elderly or unfit for more aggressive treatment.

Key Inclusion Criteria (Phase 1b Cohorts C1, C2, C3 and E1, E2, F1, F2, F3): Histologically documented relapsed/refractory Multiple Myeloma (MM).

Key Inclusion Criteria (Phase 1b Cohort D1 and D2): Pathologically confirmed relapsed/refractory diffuse large B-cell lymphoma (DLBCL)

Key Exclusion Criteria (Phase 1a and Phase 1b, all Cohorts):

1. Known, current central nervous system disease involvement.

2. Use of any investigational agent or any anticancer drug within 14 days before planned start of study treatment (within 4 weeks for antibody-based therapies and within 8 weeks for cell-based therapies).

3. Subjects who have undergone radiation therapy within 14 days of study treatment administration.

4. Hematopoietic stem cell transplant within 90 days before the planned start of study treatment or subjects with active graft-vs-host disease, with the exception of Grade 1 skin involvement.

5. Major surgery within 30 days before planned start of study treatment.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Diffuse Large B-Cell Lymphoma
• Leukemia
• Lymphoma
• Lymphoma, Large B-Cell, Diffuse
• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Maplirpacept (PF-07901801)
maplirpacept (PF-07901801) will be administered by intravenous infusion at ranging doses, as determined from sequential dosing cohorts.
• Azacitidine
intravenous (IV) or subcutaneous (SC) daily for 7 days, repeated every 4 weeks
• Venetoclax
orally daily for each day of each cycle (first 7 doses taken in clinic). The ramp-up and target dose of venetoclax will be adjusted per the package insert in subjects who are taking concomitant moderate or strong CYP3A4 inhibitors or posaconazole
• Carfilzomib
Days 1, 8, and 15 of 28-day cycles; starting dose IV given on Cycle (C) 1 Day (D) 1, and if tolerated, then increased dose via IV given starting on C1D8 and subsequent doses thereafter.
• Dexamethasone
starting dose via IV on Days 1, 8, 15, and increased dose via IV on 28-day cycles
• Anti-CD20 Targeting agent
Days 1,8,15, and 22 of the first 28-day cycle and then on Day 1 of subsequent 21-day cycles. The anti-CD20 targeting agent will be administered for a total of eight doses, and then Cohort F1, F2 and F3: TTI-622 + isatuximab, carfilzomib and dexamethasone Cohort C1, C2 and C3: TTI-622 + Carfilzomib and Dexamethasone will be continued as single-agent therapy.
• Isatuximab
F1: IV dose C0D1, C0D8, C0D15 and C0D22 (lead in phase);weekly during Cycle 1; Cycle 2 and beyond will be administered on Days 1 and 15 (Q2W). F2 and F3: IV dose C0D1 and C0D8 (lead in phase); C1D1, C1D8, C1D15 and C1D22; Cycle 2 and beyond will be administered on days 1 and 15 (Q2W). Carfilzomib: IV dose on days 1 and 2 of cycle 1; then increased IV dose on days 8, 9, 15, and 16 of cycle 1; cycle 2 and beyond: increased IV dose on days 1, 2, 8, 9, 15, and 16. Dexamethasone IV or PO on days 1, 2, 8, 9, 15, 16, 22, and 23 starting cycle 1.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Michigan Hospitals	Ann Arbor	Michigan
United States	Blood and Marrow Transplant Group of Georgia	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	Memorial Sloan Kettering Cancer Center at Basking Ridge	Basking Ridge	New Jersey
United States	Montefiore Medical Center	Bronx	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Gabrail Cancer Center Research	Canton	Ohio
United States	Novant Health Cancer Institute - Research Office	Charlotte	North Carolina
United States	Novant Health Cancer Institute Hematology - Charlotte	Charlotte	North Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	Memorial Sloan Kettering Cancer Center at Commack	Commack	New York
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	HealthONE Presbyterian/St. Luke's Medical Center	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Karmanos Cancer Institute Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Summit Medical Group Cancer Center	Florham Park	New Jersey
United States	Prisma Health, Institute for Translational Oncology Research, Clinical Research Unit	Greenville	South Carolina
United States	Prisma Health-Upstate Cancer Institute	Greenville	South Carolina
United States	Memorial Sloan Kettering Cancer Center at Westchester	Harrison	New York
United States	Oncology Consultants P.A.	Houston	Texas
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Indiana Blood & Marrow Transplantation	Indianapolis	Indiana
United States	Indiana Blood and Marrow Transplantation-Administrative Offices	Indianapolis	Indiana
United States	Indiana Blood and Marrow Transplantation-Clinic	Indianapolis	Indiana
United States	University of TN Medical Center	Knoxville	Tennessee
United States	Memorial Sloan Kettering Cancer Center - Investigational Drug Service Pharmacy	Long Island City	New York
United States	Keck Hospital of USC	Los Angeles	California
United States	LAC+USC Medical Center	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	Norton Cancer Institute, St Matthews Campus	Louisville	Kentucky
United States	Norton Cancer Institute, St. Matthews Campus, Attn. Becky Champion, PharmD	Louisville	Kentucky
United States	Norton Diagnostic Center-Dupont (PET Scans)	Louisville	Kentucky
United States	Norton Women & Children's Hospital	Louisville	Kentucky
United States	Memorial Sloan Kettering Cancer Center at Monmouth	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center at Montvale	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center (Outpatient Center)	New York	New York
United States	Memorial Sloan Kettering Cancer Center - David H. Koch Center	New York	New York
United States	Christiana Care Health Services	Newark	Delaware
United States	Christiana Care Health Services - Christiana Hospital	Newark	Delaware
United States	Christiana Care Hematology Oncology - Helen F Graham Cancer Center	Newark	Delaware
United States	Medical Oncology Hematology Consultants, PA, Helen F. Graham Cancer Center	Newark	Delaware
United States	Keck Hospital of USC Pasadena	Pasadena	California
United States	Sidney Kimmel Cancer Center, Clinical Trials Organization	Philadelphia	Pennsylvania
United States	Sidney Kimmel Cancer Center, Research Support Services	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Thomas Jefferson University - Clinical Research Institute	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Investigational Drug Services	Philadelphia	Pennsylvania
United States	Thomas Jefferson University, Investigational Drug Service	Philadelphia	Pennsylvania
United States	Thomas Jefferson University, Medical Oncology	Philadelphia	Pennsylvania
United States	West Penn Hospital	Pittsburgh	Pennsylvania
United States	Swedish Cancer Institute	Seattle	Washington
United States	Swedish Medical Center	Seattle	Washington
United States	Tampa General Hospital	Tampa	Florida
United States	Tampa General Hospital Cancer Institute	Tampa	Florida
United States	Memorial Sloan Kettering Cancer Center at Nassau	Uniondale	New York
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	Novant Health Cancer Institute - Research Office	Winston-Salem	North Carolina
United States	Novant Health Cancer Institute Hematology - Forsyth	Winston-Salem	North Carolina
United States	Novant Health Forsyth Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1a: Number of adverse events (AE) by severity	To characterize the safety profile (incidence of AEs)	Through study completion, up to 18 months
Primary	Phase 1a: Number of AEs by Frequency	To characterize the safety profile (incidence of AEs) and	Through study completion, up to 18 months
Primary	Phase 1a: Number of participants with Dose-Limiting Toxicities (DLT)	To characterize the dose limiting toxicities (DLTs) of TTI-622.	Up to 21-42 days
Primary	Phase 1b: Number of adverse events (AE) by severity	To characterize the safety profile (incidence of AEs) of TTI-622 given in combinations or as a single agent.	Through study completion, up to 30 months
Primary	Phase 1b: Number of adverse events (AE) by frequency	To characterize the safety profile (incidence of AEs) of TTI-622 given in combination or as a single agent.	Through study completion, up to 30 months
Primary	Phase 1b: Number of participants with disease response	To evaluate response rate of each combination treatment in the (7) combination cohorts (A1,A2, B1, B2, C1, C2, C3, D1, D2, F1, F2, F3) and for single agent treatment (Cohort E1 and E2). For AML, response = CR. For MM, response = CR+sCR+VGBR+PR. For DLBCL, OR=CR+PR	Through study completion, up to 30 months
Primary	Phase 1a: Maximum Tolerated Dose (MTD)	To characterize the highest dose level for which no more than 1 participant in a dose cohort experienced DLTs.	Baseline (the start of each sequentially increased treatment dose), up to the 3rd evaluable patient completes DLT observation period of 21 or 42 days.
Primary	Phase 1b: Recommended dose of TTI-622 in combination with selected anticancer treatments	To characterize the recommended dose of TTI-622 in combination with selected anticancer treatments in 5 patient populations: TTI-622 plus azacitidine in newly diagnosed TP53-mutated AML; TTI-622 plus azacitidine and venetoclax in elderly (>/= 75 years old) or unfit, newly diagnosed TP53-wildtype AML; TTI-622 plus Carfilzomib and dexamethasone in Carfilzomib-refractory, Relapsed/Refractory (R/R) multiple myeloma (MM) after 3 or more prior lines of therapy; TTI-622 plus an anti-CD20 targeting agent (such as ruxience or rituxan) in R/R CD20+ DLBCL after 1 or more prior lines of therapy; TTI-622 plus isatuximab, carfilzomib and dexamethasone in R/R MM after 1-3 prior lines of therapy	Through study completion, up to 30 months
Primary	Phase 1b: Recommended dose of TTI-622 as a single agent	To characterize the recommended dose of TTI-622 as a single agent in patients with R/R MM after 3 or more prior lines of therapy.	Through study completion, up to 30 months
Primary	Number of participants with response assessments that show preliminary efficacy	To evaluate preliminary efficacy of each combination treatment in the selected patient populations and for single-agent treatment in R/R MM	Through study completion, up to 30 months
Secondary	Phase 1a: TTI-622 PK parameter AUC0-t	To characterize AUC0-t of TTI-622.	Through study completion, up to 18 months
Secondary	Phase 1a: TTI-622 PK parameter Cmax	To characterize Cmax of TTI-622.	Through study completion, up to 18 months
Secondary	Phase 1a: Incidence of anti-drug antibodies (ADA)	To characterize the immunogenicity of TTI-622.	Through study completion, up to 18 months
Secondary	Phase 1a: Number of participants with overall response rate (ORR) for participants treated with TTI-622.	To determine the disease response.	Through study completion, up to 18 months
Secondary	Phase 1a: Number of participants with disease control rate (DCR)	To determine the disease control rate (DCR) for participants treated with TTI-622.	Through study completion, up to 18 months
Secondary	Phase 1a: Time to response (TTR)	To determine the time to response (TTR) for participants treated with TTI-622.	Through study completion, up to 18 months
Secondary	Phase 1a: Duration of Response (DR)	To determine the duration of response (DR) for participants treated with TTI-622.	Through study completion, up to 18 months
Secondary	Phase 1a: Progression free survival (PFS)	To determine the progression free survival (PFS) time for participants treated with TTI-622.	Through study completion, up to 18 months
Secondary	Phase 1b: TTI-622 PK parameter Cmax when combined with selected anticancer treatments or as a single agent	To characterize Cmax of TTI-622 when combined with selected anticancer treatments or as a single agent.	Through study completion, up to 30 months
Secondary	Phase 1b: incidence of anti-drug antibodies (ADA) Immunogenicity of TTI-622 when combined with selected anticancer treatments or as a single agent	To characterize the immunogenicity of TTI-622 when combined with selected anticancer treatments or as a single agent	Through study completion, up to 30 months
Secondary	Phase 1b: Number of participants with disease control rate (DCR)	To determine the disease control rate (DCR) for participants treated with TTI-622 when combined with selected anticancer treatments or as a single agent.	Through study completion, up to 30 months
Secondary	Phase 1b: Time to response (TTR)	To determine the time to response (TTR) for participants treated with TTI-622 when combined with selected anticancer treatments or as a single agent.	Through study completion, up to 30 months
Secondary	Phase 1b: Event-free survival (EFS)	To determine event-free survival (EFS; for Cohorts A and B) time for participants treated with TTI-622 when combined with selected anticancer treatments or as a single agent.	Through study completion, up to 30 months
Secondary	Phase 1b: Duration of response (DR)	To determine the duration of response (DOR) for participants treated with TTI-622 when combined with selected anticancer treatments or as a single agent.	Through study completion, up to 30 months
Secondary	Phase 1b: Progression-free survival (PFS)	To determine the progression-free survival (PFS) time for participants treated with TTI-622 when combined with selected anticancer treatments or as a single agent.	Through study completion, up to 30 months
Secondary	Phase 1b: Number of Participants With Minimal Residual Disease Burden (MRD) Positive, Negative and Not Evaluable (NE) Status	To determine minimal residual disease (MRD; for Cohorts A, B, C , E and F) for participants treated with TTI-622 when combined with selected anticancer treatments or as a single agent.	Through study completion, up to 30 months

External Links

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