Maplirpacept + Standard Therapies for Blood Cancers

(TTI-622-01 Trial)

No longer recruiting at 73 trial locations

Overseen By Pfizer CT.gov Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Trillium Therapeutics Inc.

Must not be taking: Investigational agents

Disqualifiers: CNS disease, recent surgery, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medicine called maplirpacept (also known as TTI-622) for individuals with various blood cancers, such as lymphoma, multiple myeloma, and acute myeloid leukemia (AML). The goal is to determine if maplirpacept, alone or with other cancer medicines, is safe and effective in controlling these cancers. In the first part (phase 1a), the medicine is administered alone to identify the safest dose. The second part (phase 1b) evaluates how well maplirpacept works with other treatments. This trial might be suitable for those with relapsed blood cancer or newly diagnosed AML who have no other treatment options. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new medicine.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have taken any investigational or anticancer drugs within 14 days before starting the study treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that maplirpacept (also known as PF-07901801) is generally well-tolerated in clinical trials. Studies indicate that this experimental medicine is safe for individuals with various blood cancers. Reports suggest it might also be safe to use maplirpacept alongside other cancer treatments. However, the safety and effectiveness of maplirpacept remain under investigation. As with any trial, side effects may occur, and participants receive close monitoring to ensure their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about maplirpacept because it offers a novel approach to treating blood cancers, such as multiple myeloma and acute myeloid leukemia. Unlike traditional therapies that often target cancer cells directly, maplirpacept works by enhancing the immune system's ability to recognize and destroy cancer cells. This is achieved through its unique action as a CD47-SIRPα pathway inhibitor, which essentially "unmasks" cancer cells, allowing the immune system to attack them more effectively. Additionally, maplirpacept is being tested both as a standalone treatment and in combination with other drugs, like isatuximab and venetoclax, potentially leading to more versatile and effective treatment options for patients.

What evidence suggests that this trial's treatments could be effective for blood cancers?

Research shows that maplirpacept (PF-07901801), which participants in this trial may receive, may help treat blood cancers like multiple myeloma, acute myeloid leukemia (AML), and diffuse large B-cell lymphoma. Lab studies have found that maplirpacept helps the immune system better locate and destroy cancer cells. It enhances a process called phagocytosis, where immune cells "eat" cancer cells. This effect has appeared in studies on both multiple myeloma and AML cells. Early results suggest it might fight cancer, but further research is needed to confirm its effectiveness. ^{1 5 6 7 8}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

Adults with advanced blood cancers like lymphoma, leukemia, and multiple myeloma who've had their disease worsen after standard treatments can join. They need a tissue sample for research, good liver/kidney/blood function, and an ECOG score of 0-2 (which measures cancer patients' daily living abilities). People can't join if they've recently had other cancer drugs or major surgery, have brain involvement by the cancer, recent radiation therapy or stem cell transplant complications.

Inclusion Criteria

My liver is working well.

My diagnosis is relapsed or refractory diffuse large B-cell lymphoma.

I have recovered from side effects of past cancer treatments to mild or my normal level.

Exclusion Criteria

I haven't taken any experimental drugs or cancer treatments recently.

I have not had major surgery in the last 30 days.

I haven't had a stem cell transplant in the last 3 months or have active graft-vs-host disease, except for mild skin issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1a Treatment

Dose-escalation phase where participants receive maplirpacept (PF-07901801) as a single agent to determine safety and maximum tolerated dose.

Up to 18 months

Weekly visits for blood tests and monitoring

Phase 1b Treatment

Participants receive maplirpacept (PF-07901801) in combination with other anticancer medicines to evaluate safety and efficacy.

Up to 30 months

Weekly visits for blood tests and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Quality-of-Life Assessment
• TTI-622

Trial Overview

The trial is testing Maplirpacept alone in phase 1a to find a safe dose for those with relapsed/refractory lymphoma or multiple myeloma. In phase 1b it's combined with other anticancer meds for newly diagnosed AML or worsening diseases. The goal is to see if these combinations are safe and help reduce cancer growth.

How Is the Trial Designed?

Group I: maplirpacept (PF-07901801) Monotherapy Experimental Treatment 1 Intervention

In the phase 1a dose- escalation part for single-agent maplirpacept (PF-07901801), participants with Relapsing or Refractory (R/R) lymphoma will be enrolled in sequential dose cohorts to receive maplirpacept (PF-07901801) QW to characterize safety, tolerability, and PK; to determine the Maximum Tolerated Dose (MTD) or P1b Starting Dose (a dose lower than or equal to the single-agent MTD), and to gain preliminary evidence of antitumor activity. In addition, participants with R/R Lymphoma may also be enrolled in a cohort to receive maplirpacept (PF-07901801) Q2W and a cohort to receive maplirpacept (PF-07901801) Q3W to characterize safety, tolerability, and PK; to determine the MTD; and to gain preliminary evidence of antitumor activity.

Group II: Cohort F1, F2 and F3: maplirpacept (PF-07901801) + isatuximab, carfilzomib and dexamethasone Experimental Treatment 4 Interventions

Cohort F1: participants with Relapsing or Recurrent (R/R) Multiple Myeloma (MM) will be treated with increasing doses of maplirpacept (PF-07901801) + isatuximab, carfilzomib and dexamethasone. Cohort F2: participants with R/R MM will be treated with maplirpacept (PF-07901801) QW + isatuximab, carfilzomib and dexamethasone. Cohort F3: participants with R/R MM will be treated with maplirpacept (PF-07901801) increased dose QW + isatuximab, carfilzomib and dexamethasone.

Group III: Cohort E1 and E2: single agent maplirpacept (PF-07901801) Experimental Treatment 1 Intervention

Cohort E1: participants with Relapsing or Recurrent (R/R) Multiple Myeloma (MM) will be treated with single agent maplirpacept (PF-07901801) QW. Cohort E2: participants with R/R MM will be treated with single agent maplirpacept (PF-07901801) increased dose QW.

Group IV: Cohort D1 and D2: maplirpacept (PF-07901801) + an anti-CD20 targeting agent Experimental Treatment 2 Interventions

Cohort D1: participants with Relapsing or Recurrent (R/R) CD20+ Diffuse Large B Cell Lymphoma (DLBCL) will be treated with maplirpacept (PF-07901801) QW, then an increased dose Q3W + an anti-CD20 targeting agent. Cohort D2: participants with R/R CD20+ DLBCL will be treated with maplirpacept (PF-07901801) dosed QW for 4 weeks, then an increased dose Q3W + an anti-CD20 targeting agent.

Group V: Cohort C1, C2 and C3: maplirpacept (PF-07901801) + Carfilzomib and Dexamethasone Experimental Treatment 3 Interventions

Cohort C1: participants with Relapsing or Refractory (R/R) Multiple Myeloma (MM) will be treated with maplirpacept (PF-07901801) QW \+ carfilzomib and dexamethasone. Cohort C2: participants with R/R MM will be treated with maplirpacept (PF-07901801) QW + carfilzomib and dexamethasone. Cohort C3: participants with R/R MM will be treated with maplirpacept (PF-07901801) Q2W + carfilzomib and dexamethasone.

Group VI: Cohort B: maplirpacept (PF-07901801) + Azacitidine and Venetoclax Experimental Treatment 3 Interventions

Cohort B1: elderly or unfit participants with newly diagnosed TP53-wildtype AML will be treated with maplirpacept (PF-07901801) QW + azacitidine and venetoclax Cohort B2: elderly or unfit participants with newly diagnosed TP53-wildtype AML will be treated with maplirpacept (PF-07901801) QW + azacitidine and venetoclax.

Group VII: Cohort A: maplirpacept (PF-07901801) + Azacitidine Experimental Treatment 2 Interventions

Cohort A1: participants with newly diagnosed TP53-mutated Acute Myelocytic Leukemia (AML) will be treated with maplirpacept (PF-07901801) QW + azacitidine. Cohort A2: participants with newly diagnosed TP53-mutated AML will be treated with maplirpacept (PF-07901801) QW + azacitidine.

Who Is Running the Clinical Trial?

Trillium Therapeutics Inc.

Lead Sponsor

Trials

7

Recruited

620+

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Trillium Therapeutics, Inc., a Pfizer Company

Collaborator

Trials

1

Recruited

190+

Published Research Related to This Trial

Olverembatinib (HQP1351) is a third-generation tyrosine kinase inhibitor specifically designed to target BCR-ABL1 mutations, including the T315I mutation that causes resistance to earlier treatments, making it a promising option for patients with chronic myeloid leukaemia (CML).

In November 2021, olverembatinib was approved in China for adult patients with TKI-resistant chronic-phase or accelerated-phase CML harboring the T315I mutation, indicating its efficacy in overcoming resistance that limits other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olverembatinib: First Approval. Dhillon, S.[2022]

Citations

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clinicaltrials.gov

clinicaltrials.gov/study/NCT03530683

NCT03530683 | A Clinical Trial to Learn About the Study ...

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

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11897230/

a CD47 decoy receptor with minimal red blood cell binding ...

Maplirpacept has limited binding to RBCs while driving enhanced macrophage-mediated phagocytosis of hematological tumor cells in vitro and reducing tumor ...

3.

pharmaceutical-technology.com

pharmaceutical-technology.com/data-insights/maplirpacept-pfizer-acute-myelocytic-leukemia-aml-acute-myeloblastic-leukemia-likelihood-of-approval/

Maplirpacept by Pfizer for Acute Myelocytic Leukemia (AML ...

Maplirpacept is under clinical development by Pfizer and currently in Phase II for Acute Myelocytic Leukemia (AML, Acute Myeloblastic Leukemia).

4.

cdn.clinicaltrials.gov

cdn.clinicaltrials.gov/large-docs/90/NCT05261490/Prot_000.pdf

Investigational Product TTI-622 (SIRPα-IgG4 Fc)/PF- ...

This study will investigate a new therapeutic regimen for participants with platinum-resistant recurrent epithelial ovarian cancer (EOC), defined as disease ...

5.

clinicaltrials.eu

clinicaltrials.eu/inn/maplirpacept/

MAPLIRPACEPT – Application in Therapy and Current Clinical ...

With azacitidine and venetoclax: For newly diagnosed acute myeloid leukemia (AML). Azacitidine is a hypomethylating agent, and venetoclax is a BCL-2 inhibitor.

6.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS7595

TTI-622-01: A phase 1a/1b dose-escalation and expansion ...

Here we describe 2 cohorts within the phase 1b part of the study that are intended to determine the safety and preliminary efficacy of TTI-622 ...

7.

clin.larvol.com

clin.larvol.com/trial-detail/NCT03530683

A Clinical Trial to Learn About the Study Medicine Called ...

Updated safety data demonstrate that TTI-621 is generally well tolerated....A two-part, multicenter, open-label, phase 1a/1b study of TTI-622 in patients with ...

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pfizeroncologydevelopment.com

pfizeroncologydevelopment.com/molecule/sirpa-igg4-fusion-protein

Maplirpacept (TTI-622 | PF-07901801)

Maplirpacept (TTI-622 | PF-07901801) is an investigational compound. Its safety and efficacy have not been established. Go to section ...