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

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.

Conditions

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

Interventions

DRUG

Maplirpacept (PF-07901801)

maplirpacept (PF-07901801) will be administered by intravenous infusion at ranging doses, as determined from sequential dosing cohorts.

DRUG

Azacitidine

intravenous (IV) or subcutaneous (SC) daily for 7 days, repeated every 4 weeks

DRUG

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

DRUG

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.

DRUG

Dexamethasone

starting dose via IV on Days 1, 8, 15, and increased dose via IV on 28-day cycles

DRUG

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.

DRUG

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.

Sponsors & Collaborators

• Pfizer

  lead INDUSTRY

Principal Investigators

• Pfizer CT.gov Call Center · Pfizer

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-05-14

Primary Completion

2024-07-18

Completion

2024-07-18

FDA Drug

Yes

Countries

• United States

Study Locations