Maplirpacept + Standard Therapies for Blood Cancers

(TTI-622-01 Trial)

Recruiting at 71 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

189 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new medicine called maplirpacept (PF-07901801) for adults with certain blood cancers that have not responded to other treatments. The medicine is given through a vein and aims to attack cancer cells. The study will see how safe and effective it is when used alone or with other cancer medicines.

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.

What data supports the effectiveness of the drug Maplirpacept + Standard Therapies for Blood Cancers?

The research suggests that combining different therapies, like tyrosine kinase inhibitors (TKIs) with other agents, can improve outcomes in blood cancers by overcoming resistance and enhancing treatment effectiveness. For example, combining copanlisib with TKIs has shown to reduce tumor growth and increase survival in resistant leukemia models, indicating that similar combination strategies might be effective for other blood cancer treatments. ^{1 2 3 4 5}

What makes the drug TTI-622 unique for treating blood cancers?

TTI-622 is unique because it is designed to enhance the immune system's ability to fight cancer by blocking a protein that usually helps cancer cells evade immune detection, which is different from traditional treatments that often target cancer cells directly. ^{6 7 8 9 10}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Interferon-α may help prevent molecular relapse of chronic myeloid leukemia after the discontinuation of tyrosine kinase inhibitors. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Combination therapy with copanlisib and ABL tyrosine kinase inhibitors against Philadelphia chromosome-positive resistant cells. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Use of tyrosine kinase inhibitors for paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia: a systematic review and meta-analysis. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Improving Outcomes in Chronic Myeloid Leukemia Over Time in the Era of Tyrosine Kinase Inhibitors. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Current management of Philadelphia chromosome positive ALL and the role of stem cell transplantation. [2019]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Olverembatinib: First Approval. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Long-term tolerability and efficacy after initial PegIFN-α addition to dasatinib in CML-CP: Five-year follow-up of the NordCML007 study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Blinatumomab administered concurrently with oral tyrosine kinase inhibitor therapy is a well-tolerated consolidation strategy and eradicates measurable residual disease in adults with Philadelphia chromosome positive acute lymphoblastic leukemia. [2020]

9. England pubmed.ncbi.nlm.nih.gov

The clonal evolution of two distinct T315I-positive BCR-ABL1 subclones in a Philadelphia-positive acute lymphoblastic leukemia failing multiple lines of therapy: a case report. [2018]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Bosutinib: Pediatric First Approval. [2023]