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.
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Pfizer
- Enrollment
- 10
- Locations
- 14
- Primary Endpoint
- PART 1 & 2: Incidence of Adverse Events (AE)s
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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: sasanlimab (Biological)
Part 1A: PF-07826390 Monotherapy
PF-07826390 monotherapy at prescribed dose and frequency in 28-day cycles
Intervention: PF-07826390 (Drug)
Part 1B: PF-07826390 + sasanlimab
PF-07826390 + sasanlimab at prescribed dose and frequency in 28-day cycles
Intervention: PF-07826390 (Drug)
Part 1B: PF-07826390 + sasanlimab
PF-07826390 + sasanlimab at prescribed dose and frequency in 28-day cycles
Intervention: sasanlimab (Biological)
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: PF-07826390 (Drug)
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: sasanlimab (Biological)
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: PF-07826390 (Drug)
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: sasanlimab (Biological)
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: PF-07826390 (Drug)
Part 2B: PF-07826390
PF-07826390 dose expansion in NSCLC 2L+ at prescribed dose and frequency in 28-day cycles
Intervention: PF-07826390 (Drug)
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: PF-07826390 (Drug)
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: SOC (anti-PD-1 + platinum -based chemo) (Other)
Outcomes
Primary Outcomes
PART 1 & 2: Incidence of Adverse Events (AE)s
Time Frame: From start of the treatment and up to 90 days after last dose or start of new anticancer therapy, whichever occurred first.
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.
PART 1 & 2: Number of participants with laboratory abnormalities
Time Frame: From start of the treatment and up to 90 days after last dose or start of new anticancer therapy, whichever occurred first.
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).
PART 1: Number of participants with Dose-limiting toxicities (DLT)
Time Frame: First cycle, Day 1 up to Day 28
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.
Part 2: Objective Response - Number of Participants With Objective Response
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.
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.
Secondary Outcomes
- Part 1: Maximum Observed Serum Concentration (Cmax)(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))
- Time to event endpoints: duration of response (DOR) by RECIST v1.1(Baseline to confirmed disease progression, up to 2 years after the last dose of study treatment)
- Part 1: Time to Reach Maximum Serum Concentration (Tmax) of PF-07826390(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))
- Part 1 and Part 2: Incidence and titers of antidrug antibodies (ADA) against PF-07826390(Prior to dosing at Cycle 1+ Day 1 up to end of study treatment, approximately 2 years (each cycle is 28 days))
- Part 1: Serum Area Under the Curve From Time Zero to Last Time Zero to clearance (CL/F) of PF-07826390(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))
- Part 2: Serum Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-07826390(Cycle 1 Day 1 until last dose of study treatment, approximately 2 years (each cycle is 28 days))
- Part 2: Serum under the curve terminal elimination half life (T ½) of PF-07826390(Cycle 1 Day 1 until last dose of study treatment, approximately 2 years (each cycle is 28 days))
- Objective Response - Number of Participants with Objective Response(Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion, approximately 2 years)
- Time to event endpoints: progression-free survival (PFS) by RECIST v1.1(Baseline to confirmed disease progression, up to 2 years after the last dose of study treatment)
- Part 1: Serum Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-07826390(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))
- Part 2: Maximum Observed Serum Concentration (Cmax) of PF-07826390(Cycle 1 Day 1 until last dose of study treatment, approximately 2 years (each cycle is 28 days))
- Part 2: Serum under the curve apparent volume of distribution during terminal phase (Vz/F) of PF-07826390(Cycle 1 Day 1 until last dose of study treatment, approximately 2 years (each cycle is 28 days))
- Part 1: Serum under the curve apparent volume of distribution during terminal phase (Vz/F) of PF-07826390(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))
- Part 1 and Part 2: Serum Concentrations of PF-07826390 in combination (Part 1B, 2A and 2C)(Prior to dosing at Cycle 1+ Day 1 until last dose of study treatment, approximately 2 years (each cycle is 28 days))
- Part 2: Time to Reach Maximum Serum Concentration (Tmax) of PF-07826390(Cycle 1 Day 1 until last dose of study treatment, approximately 2 years (each cycle is 28 days))
- Part 1: Serum under the curve terminal elimination half life (T ½) of PF-07826390(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))
- Part 1 and Part 2: Paried Tumor Biopsies(Baseline through Cycle 2 Day 15 (each cycle is 28 days))
- Part 1: Pharmacodynamic blood samples: Receptor occupancy(Cycle 1 Day 1 until last dose of study treatment, approximately 2 years (each cycle is 28 days))
- Part 2: Pharmacodynamic blood samples Receptor Occupancy(Cycle 1 Day 1 until last dose of study treatment, approximately 2 years (each cycle is 28 days))
- Part 2: Serum Area Under the Curve From Time Zero to clearance (CL/F) of PF-07826390(Cycle 1 Day 1 until last dose of study treatment, approximately 2 years (each cycle is 28 days))