The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.
Maplirpacept (TTI-622/PF-07901801) is an investigational compound. Its safety and efficacy have not been established.
Active Not-enrolling
United States
EXPERIMENTAL: maplirpacept (PF-07901801) Monotherapy
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.
DRUG: Maplirpacept (PF-07901801)
maplirpacept (PF-07901801) will be administered by intravenous infusion at ranging doses, as determined from sequential dosing cohorts.
EXPERIMENTAL: Cohort A: maplirpacept (PF-07901801) + Azacitidine
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.
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
EXPERIMENTAL: Cohort B: maplirpacept (PF-07901801) + Azacitidine and Venetoclax
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.
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
EXPERIMENTAL: Cohort D1 and D2: maplirpacept (PF-07901801) + an anti-CD20 targeting agent
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.
DRUG: Maplirpacept (PF-07901801)
maplirpacept (PF-07901801) will be administered by intravenous infusion at ranging doses, as determined from sequential dosing cohorts.
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.
EXPERIMENTAL: Cohort E1 and E2: single agent maplirpacept (PF-07901801)
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.
DRUG: Maplirpacept (PF-07901801)
maplirpacept (PF-07901801) will be administered by intravenous infusion at ranging doses, as determined from sequential dosing cohorts.
EXPERIMENTAL: Cohort F1, F2 and F3: maplirpacept (PF-07901801) + isatuximab, carfilzomib and dexamethasone
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.
DRUG: Maplirpacept (PF-07901801)
maplirpacept (PF-07901801) will be administered by intravenous infusion at ranging doses, as determined from sequential dosing cohorts.
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: 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.
EXPERIMENTAL: Cohort C1, C2 and C3: maplirpacept (PF-07901801) + Carfilzomib and Dexamethasone
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.
DRUG: Maplirpacept (PF-07901801)
maplirpacept (PF-07901801) will be administered by intravenous infusion at ranging doses, as determined from sequential dosing cohorts.
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
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):
Phase 1a: Number of adverse events (AE) by severity
To characterize the safety profile (incidence of AEs)
Through study completion, up to 18 months
Phase 1a: Number of AEs by Frequency
To characterize the safety profile (incidence of AEs) and
Through study completion, up to 18 months
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
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
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
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
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.
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
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
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
Phase 1a: TTI-622 PK parameter AUC0-t
To characterize AUC0-t of TTI-622.
Through study completion, up to 18 months
Phase 1a: TTI-622 PK parameter Cmax
To characterize Cmax of TTI-622.
Through study completion, up to 18 months
Phase 1a: Incidence of anti-drug antibodies (ADA)
To characterize the immunogenicity of TTI-622.
Through study completion, up to 18 months
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
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
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
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
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
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
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
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
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
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
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
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
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
177
Sponsor: Pfizer
Collaborator: None
For more information, call or email the Pfizer Clinical Trial Contact Center:
When calling, please reference this study number:
NCT# stands for National Clinical Trial number. This is a unique identification code given to each clinical trial registered on ClinicalTrials.gov. The format is "NCT" followed by an 8-digit number (for example, NCT00000419). Also called the ClinicalTrials.gov identifier.
NCT03530683
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