Clinical trial NCT06546553: A Study to Learn About How Different Amounts of the Study Medicine PF-07826390 Act in the Body of People With Cancer When Taken Alone or With Other Anti-cancer Medicines.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Neoplasms
Non-small-cell Lung Cancer
Squamous Cell Carcinoma of the Head and Neck
Renal Cell Carcinoma
Colorectal Carcinoma
Ovarian Carcinoma
Keywords: Solid tumors
metastatic
advanced
micro satellite stable
anti-PD-1
PF-07282690
LILRB12
sasanlimab
PD-1 resistance
PD-1 naive
PDx resistance
PDxnaive
Carcinoma, Non-Small Cell Lung
Non-Small Cell Lung Cancer
Non-Small Cell Lung Carcinoma
Non-Small-Cell Lung Carcinoma
Nonsmall Cell Lung Cancer
Colorectal Cancer
Colorectal Neoplasms
Colorectal Carcinoma
Colorectal Tumors
Renal Cell Carcinoma
Kidney Neoplasms
Rectal Disease
Neoplasms, Colorectal
Malignant Melanoma
Microsatellite Stable Colorectal Cancer (MSS CRC)
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2024-08-09
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to learn about the:

* safety (the effect of the study medicine on the participant's body),
* effects of the study medicine alone or in combination with sasanlimab -
* the best amount of the study medicine.

This study is seeking participants who have solid tumors (An abnormal mass of tissue) that:

* have advanced (cancer that does not disappear or stay away with treatment) or
* are metastatic (has spread to other parts of the body).

This includes (but limited to) the following cancer types:

* Non-Small Cell Lung Cancer (NSCLC): It's a type of lung cancer where the cells grow slowly but often spread to other parts of the body.
* Colorectal Cancer (CRC): This is a disease where cells in the colon or rectum grow out of control.
* Renal Cell Carcinoma (RCC): This is a cancer that starts in the kidney.

All participants in this study will receive the study medication (PF-07826390) as an IV infusion (given directly into a vein) at the study once every four weeks in 28 day cycles.

The study participants depending on the group enrolled in, will receive the study medication (PF-07826390 alone or in combination with other anti-cancer medications (sasanlimab). Sasanlimab is given as a shot under the skin every 4 weeks.

Participants can continue to take the study medication (PF-07826390) until their cancer is no longer responding. Participants who are taking sasanlimab may receive it for up to 2 years.

The study will look at the experiences of people receiving the study medicines. This will help see if the study medicines are safe and effective.

Participants will be involved in this study for up to 4 years. During this time, participants will have a study visit every week. The participants after stopping the study medicine (at about 2 years) will be followed for another two years to see how the participants are doing.


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

Primary outcomes:
measure: PART 1: Number of participants with Dose-limiting toxicities (DLT)
timeFrame: First cycle, Day 1 up to Day 28
measure: PART 1 & 2: Incidence of Adverse Events (AE)s
timeFrame: From start of the treatment and up to 90 days after last dose or start of new anticancer therapy, whichever occurred first.
measure: PART 1 & 2: Number of participants with laboratory abnormalities
timeFrame: From start of the treatment and up to 90 days after last dose or start of new anticancer therapy, whichever occurred first.
measure: Part 2: Objective Response - Number of Participants With Objective Response
timeFrame: Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion, approximately 2 years.
Secondary outcomes:
measure: Objective Response - Number of Participants with Objective Response
timeFrame: Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion, approximately 2 years
measure: Time to event endpoints: duration of response (DOR) by RECIST v1.1
timeFrame: Baseline to confirmed disease progression, up to 2 years after the last dose of study treatment
measure: Time to event endpoints: progression-free survival (PFS) by RECIST v1.1
timeFrame: Baseline to confirmed disease progression, up to 2 years after the last dose of study treatment
measure: Part 1: Maximum Observed Serum Concentration (Cmax)
timeFrame: 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)
measure: Part 1: Time to Reach Maximum Serum Concentration (Tmax) of PF-07826390
timeFrame: 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)
measure: Part 1: Serum Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-07826390
timeFrame: 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)
measure: Part 1: Serum Area Under the Curve From Time Zero to Last Time Zero to clearance (CL/F) of PF-07826390
timeFrame: 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)
measure: Part 1: Serum under the curve apparent volume of distribution during terminal phase (Vz/F) of PF-07826390
timeFrame: 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)
measure: Part 1: Serum under the curve terminal elimination half life (T ½) of PF-07826390
timeFrame: 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)
measure: Part 1 and Part 2: Serum Concentrations of PF-07826390 in combination (Part 1B, 2A and 2C)
timeFrame: Prior to dosing at Cycle 1+ Day 1 until last dose of study treatment, approximately 2 years (each cycle is 28 days)
measure: Part 1 and Part 2: Incidence and titers of antidrug antibodies (ADA) against PF-07826390
timeFrame: Prior to dosing at Cycle 1+ Day 1 up to end of study treatment, approximately 2 years (each cycle is 28 days)
measure: Part 1 and Part 2: Paried Tumor Biopsies
timeFrame: Baseline through Cycle 2 Day 15 (each cycle is 28 days)
measure: Part 2: Time to Reach Maximum Serum Concentration (Tmax) of PF-07826390
timeFrame: Cycle 1 Day 1 until last dose of study treatment, approximately 2 years (each cycle is 28 days)
measure: Part 2: Maximum Observed Serum Concentration (Cmax) of PF-07826390
timeFrame: Cycle 1 Day 1 until last dose of study treatment, approximately 2 years (each cycle is 28 days)
measure: Part 1: Pharmacodynamic blood samples: Receptor occupancy
timeFrame: Cycle 1 Day 1 until last dose of study treatment, approximately 2 years (each cycle is 28 days)
measure: Part 2: Pharmacodynamic blood samples Receptor Occupancy
timeFrame: Cycle 1 Day 1 until last dose of study treatment, approximately 2 years (each cycle is 28 days)
measure: Part 2: Serum Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-07826390
timeFrame: Cycle 1 Day 1 until last dose of study treatment, approximately 2 years (each cycle is 28 days)
measure: Part 2: Serum Area Under the Curve From Time Zero to clearance (CL/F) of PF-07826390
timeFrame: Cycle 1 Day 1 until last dose of study treatment, approximately 2 years (each cycle is 28 days)
measure: Part 2: Serum under the curve apparent volume of distribution during terminal phase (Vz/F) of PF-07826390
timeFrame: Cycle 1 Day 1 until last dose of study treatment, approximately 2 years (each cycle is 28 days)
measure: Part 2: Serum under the curve terminal elimination half life (T ½) of PF-07826390
timeFrame: Cycle 1 Day 1 until last dose of study treatment, approximately 2 years (each cycle is 28 days)
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Beverly Hills Cancer Center
state: California
city: Orlando
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Orlando
country: United States
facility: Sarah Cannon Research Institute at Florida Cancer Specialists
state: Florida
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Philadelphia
country: United States
facility: Thomas Jefferson University Honickman Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University, Bodine Center for Radiation Therapy
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University, Gibbon Building
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University, Sidney Kimmel Cancer Center
state: Pennsylvania
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics (START)
state: Texas
city: West Valley City
country: United States
facility: START Mountain Region
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: