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.

Clinical Trial Details

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Molecule overview Clinical trials

Other or Multiple Cancer Types

LILRB1/2 Bispecific IgG1 Antibody

PF-07826390 is an investigational compound. Its safety and efficacy have not been established.

FIRST-IN-HUMAN (FIH), OPEN-LABEL, PHASE 1 DOSE ESCALATION AND EXPANSION STUDY DESIGNED TO EVALUATE THE SAFETY, TOLERABILITY, PK, PD, AND PRELIMINARY CLINICAL ACTIVITY OF PF-07826390 AS A SINGLE AGENT OR IN COMBINATION TREATMENT FOR PARTICIPANTS WITH ADVANCED SOLID TUMORS.

Phase 1

NCT06546553

Active enrolling

Locations

United States

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Study design Key eligibility criteria Key dates Key endpoints Number of participants Collaborators and investigators

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Study design

Participant Group/Arm

EXPERIMENTAL: Part 1A: PF-07826390 Monotherapy

PF-07826390 monotherapy at prescribed dose and frequency in 28-day cycles

Intervention/Treatment

DRUG: PF-07826390

PF-07826390 is a novel, fully humanized bispecific IgG1 that targets the leukocyte immunoglobulin-like receptor, LILRB1 and LILRB2 (B1 and B2) cell-surface receptors

Participant Group/Arm

EXPERIMENTAL: Part 1B: PF-07826390 + sasanlimab

PF-07826390 + sasanlimab at prescribed dose and frequency in 28-day cycles

Intervention/Treatment

DRUG: PF-07826390

PF-07826390 is a novel, fully humanized bispecific IgG1 that targets the leukocyte immunoglobulin-like receptor, LILRB1 and LILRB2 (B1 and B2) cell-surface receptors

BIOLOGICAL: sasanlimab

A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/L2

Participant Group/Arm

EXPERIMENTAL: Part 2A (Arm 1): PF-07826390 + sasanlimab

PF-07826390 + sasanlimab dose expansion in NSCLC 2L+ at prescribed dose and frequency in 28-day cycles

Intervention/Treatment

DRUG: PF-07826390

PF-07826390 is a novel, fully humanized bispecific IgG1 that targets the leukocyte immunoglobulin-like receptor, LILRB1 and LILRB2 (B1 and B2) cell-surface receptors

BIOLOGICAL: sasanlimab

A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/L2

Participant Group/Arm

EXPERIMENTAL: Part 2A (Arm 2): PF-07826390 + sasanlimab

PF-07826390 + sasanlimab dose expansion in MSS CRC 2L+ at prescribed dose and frequency in 28-day cycles

Intervention/Treatment

DRUG: PF-07826390

PF-07826390 is a novel, fully humanized bispecific IgG1 that targets the leukocyte immunoglobulin-like receptor, LILRB1 and LILRB2 (B1 and B2) cell-surface receptors

BIOLOGICAL: sasanlimab

A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/L2

Participant Group/Arm

EXPERIMENTAL: Part 2A (Arm 3): PF-07826390 + sasanlimab

PF-07826390 + sasanlimab dose expansion in RCC 2L+ at prescribed dose and frequency in 28-day cycles

Intervention/Treatment

DRUG: PF-07826390

PF-07826390 is a novel, fully humanized bispecific IgG1 that targets the leukocyte immunoglobulin-like receptor, LILRB1 and LILRB2 (B1 and B2) cell-surface receptors

BIOLOGICAL: sasanlimab

A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/L2

Participant Group/Arm

EXPERIMENTAL: Part 2B: PF-07826390

PF-07826390 dose expansion in NSCLC 2L+ at prescribed dose and frequency in 28-day cycles

Intervention/Treatment

DRUG: PF-07826390

PF-07826390 is a novel, fully humanized bispecific IgG1 that targets the leukocyte immunoglobulin-like receptor, LILRB1 and LILRB2 (B1 and B2) cell-surface receptors

Participant Group/Arm

EXPERIMENTAL: Part 2C: PF-07826390 + SOC

PF-07826390 + SOC (anti-PD-1 + platinum -based chemo) dose expansion for a PDx-naive NSCLC 1L at prescribed dose and frequency in 28-day cycles

Intervention/Treatment

DRUG: PF-07826390

PF-07826390 is a novel, fully humanized bispecific IgG1 that targets the leukocyte immunoglobulin-like receptor, LILRB1 and LILRB2 (B1 and B2) cell-surface receptors

OTHER: SOC (anti-PD-1 + platinum -based chemo)

Standard of Care (anti-PD-1 + platinum -based chemo)

Study design table for Clinical Trial

Key eligibility criteria

Inclusion criteria

Histological or cytological diagnosis of advanced, unresectable, and/or metastatic or relapsed/refractory solid tumor
Part 1A: Participants with solid tumors where anti-PD-(L)1 is an established treatment. Participants must have progressed on or following prior anti-PD-(L)1 therapy if approved, available, tolerable, and eligible
Part 1B: Participants either meeting Part 1A criterion, or participants with "cold" solid tumors where anti-PD-(L)1 therapy is not an established treatment
Part 2: Participants with NSCLC (2A Arm 1 and 2B) must have received platinum-based chemotherapy and anti-PD-(L)1 or have intolerability to or refusal of standard therapies. Participants with NSCLC who have not been previously treated with a prior anti-pd-(L) will be enrolled in Part 2C.
Participants with MSS CRC (Part 2A Arm 2) must have received fluoropyrimidine-, oxaliplatin, and irinotecan-based chemotherapy, an anti-VEGF agent and anti-EGFR inhibitor (if RAS wildtype) and/or other molecularly targeted therapy if appropriate. Participants with RCC (Part 2A Arm 3) must have received prior tyrosine kinase inhibitor (TKI), anti-PD-(L)1 (if not receiving anti-PD-1 on protocol), anti-CTLA-4 (optional), hypoxia-inducible factor 2 alpha (HIF2a) inhibitor, or mTOR inhibitor or have documented intolerance to the standard therapy.
At least 1 measurable lesion based on RECIST 1.1 that has not been previously irradiated (Part 1 exceptions permitted after review and approval)
Able to provide pre-treatment (and optional on-treatment) tumor tissue

Exclusion criteria

Treatment with any systemic anticancer therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to planned first dose
Active or history of clinically significant autoimmune disease or other medical condition that required chronic systemic immunosuppressive therapy within recent 2 years
Prior treatment with another LILRB1 (ILT2), LILRB2 (ILT4), and/or LILRB1/2 (B1 and B2) antagonist antibodies or pathway targeting agents, including HLA conformers and HLA-G antibodies.
Lack of adequate organ (bone marrow, renal, liver) function
History of severe immune-mediated adverse event or cytokine release syndrome that was considered related to prior immune modulatory therapy that required immunosuppressive therapy

Key dates

Study start date

September 2024

Estimated Study Completion Date

February 2030

Key endpoints

Primary Outcome Measures

Outcome Measure

PART 1: Number of participants with Dose-limiting toxicities (DLT)

Measure Description

Any of the prespecified AEs that are attributable to one, the other, or both study treatments, occurring in the DLT observation period are considered DLTs, excluding toxicities clearly due to underlying disease or extraneous causes.

Time Frame

First cycle, Day 1 up to Day 28

Outcome Measure

PART 1 & 2: Incidence of Adverse Events (AE)s

Measure Description

An adverse event (AE) is any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it. SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/ incapacity; congenital anomaly. AEs included both serious and all non-serious AEs.

Time Frame

From start of the treatment and up to 90 days after last dose or start of new anticancer therapy, whichever occurred first.

Outcome Measure

PART 1 & 2: Number of participants with laboratory abnormalities

Measure Description

Number of participants with laboratory test abnormalities. Laboratory test parameters included hematology, coagulation, liver function, renal function, electrolytes, clinical chemistry, and urinalysis (dipstick and microscopy).

Time Frame

From start of the treatment and up to 90 days after last dose or start of new anticancer therapy, whichever occurred first.

Outcome Measure

Part 2: Objective Response - Number of Participants With Objective Response

Measure Description

Percentage of participants with objective response-based assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) assessed by the Investigator.

Time Frame

Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion, approximately 2 years.

Primary Outcome Measures table for Clinical Trial

Secondary Outcome Measures:

Outcome Measure

Objective Response - Number of Participants with Objective Response

Measure Description

Time Frame

Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion, approximately 2 years

Outcome Measure

Time to event endpoints: duration of response (DOR) by RECIST v1.1

Measure Description

Time to event: DOR according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as assessed by the Investigator.

Time Frame

Baseline to confirmed disease progression, up to 2 years after the last dose of study treatment

Outcome Measure

Time to event endpoints: progression-free survival (PFS) by RECIST v1.1

Measure Description

Time to event: PFS according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as assessed by the Investigator.

Time Frame

Baseline to confirmed disease progression, up to 2 years after the last dose of study treatment

Outcome Measure

Part 1: Maximum Observed Serum Concentration (Cmax)

Measure Description

Cycle 1: Pre-dose, 1, 4, 8, 24, 48, 168, 336 and 504 hours post dose. Cycle 2: Pre-dose and 336 hours post dose. Cycle 3: Pre-dose, 1, 4, 24, 168 and 336 hours post dose. Cycle 3 and beyond Pre-dose only.

Time Frame

Cycle 1 Day 1, 2, 3, 8, 15 and 22; Cycle 2 Day 1 and 15; Cycle 3+ Day 1 (each cycle is 28 days)

Outcome Measure

Part 1: Time to Reach Maximum Serum Concentration (Tmax) of PF-07826390

Measure Description

Time Frame

Cycle 1 Day 1, 2, 3, 8, 15 and 22; Cycle 2 Day 1 and 15; Cycle 3+ Day 1 (each cycle is 28 days)

Outcome Measure

Part 1: Serum Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-07826390

Measure Description

Time Frame

Cycle 1 Day 1, 2, 3, 8, 15 and 22; Cycle 2 Day 1 and 15; Cycle 3+ Day 1 (each cycle is 28 days)

Outcome Measure

Part 1: Serum Area Under the Curve From Time Zero to Last Time Zero to clearance (CL/F) of PF-07826390

Measure Description

Time Frame

Cycle 1 Day 1, 2, 3, 8, 15 and 22; Cycle 2 Day 1 and 15; Cycle 3+ Day 1 (each cycle is 28 days)

Outcome Measure

Part 1: Serum under the curve apparent volume of distribution during terminal phase (Vz/F) of PF-07826390

Measure Description

Time Frame

Cycle 1 Day 1, 2, 3, 8, 15 and 22; Cycle 2 Day 1 and 15; Cycle 3+ Day 1 (each cycle is 28 days)

Outcome Measure

Part 1: Serum under the curve terminal elimination half life (T ½) of PF-07826390

Measure Description

Time Frame

Cycle 1 Day 1, 2, 3, 8, 15 and 22; Cycle 2 Day 1 and 15; Cycle 3+ Day 1 (each cycle is 28 days)

Outcome Measure

Part 1 and Part 2: Serum Concentrations of PF-07826390 in combination (Part 1B, 2A and 2C)

Measure Description

Day 1 (all cycles) and EOT.

Time Frame

Prior to dosing at Cycle 1+ Day 1 until last dose of study treatment, approximately 2 years (each cycle is 28 days)

Outcome Measure

Part 1 and Part 2: Incidence and titers of antidrug antibodies (ADA) against PF-07826390

Measure Description

Day 1 (all cycles) and end of treatment

Time Frame

Prior to dosing at Cycle 1+ Day 1 up to end of study treatment, approximately 2 years (each cycle is 28 days)

Outcome Measure

Part 1 and Part 2: Paried Tumor Biopsies

Measure Description

Pre-dose and C2 Day 15

Time Frame

Baseline through Cycle 2 Day 15 (each cycle is 28 days)

Outcome Measure

Part 2: Time to Reach Maximum Serum Concentration (Tmax) of PF-07826390