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
Geo Regions
Back
Other or Multiple Cancer Types
STING Agonist
PF-07820435 is an investigational compound. Its safety and efficacy have not been established.
A PHASE 1 DOSE ESCALATION AND EXPANSION STUDY TO EVALUATE SAFETY, TOLERABILITY, PHARMACOKINETIC, PHARMACODYNAMIC, AND ANTITUMOR ACTIVITY OF PF-07820435 AS MONOTHERAPY AND IN COMBINATION IN PARTICIPANTS WITH ADVANCED SOLID TUMORS
Phase 1
NCT06285097
Active enrolling
Locations
United States, Japan, Puerto Rico
Study design
Participant Group/Arm
EXPERIMENTAL: Monotherapy dose escalation (Part 1A)
Participants will receive PF-07820435 orally at the prescribed dose and frequency in 28-day cycles
Intervention/Treatment
DRUG: PF-07820435
immune agonist
Participant Group/Arm
EXPERIMENTAL: Combination dose escalation (Part 1B)
Participants will receive PF-07820435 orally at the prescribed dose and frequency, in combination with sasanlimab (subcutaneous injection) at a fixed dose once every 4 weeks in 28-day cycles
Intervention/Treatment
DRUG: PF-07820435
immune agonist
BIOLOGICAL: Sasanlimab
A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/L2
Participant Group/Arm
EXPERIMENTAL: Expansion (Part 2) - Tumor specific Arm A
Participants will receive PF-07820435 orally at the prescribed dose and frequency in combination with sasanlimab SC once every 4 weeks in 28-day cycles
Intervention/Treatment
DRUG: PF-07820435
immune agonist
BIOLOGICAL: Sasanlimab
A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/L2
Participant Group/Arm
EXPERIMENTAL: Expansion (Part 2) - Tumor specific Arm B
Participants will receive PF-07820435 orally at the prescribed dose and frequency in combination with sasanlimab SC once every 4 weeks in 28-day cycles
Intervention/Treatment
DRUG: PF-07820435
immune agonist
BIOLOGICAL: Sasanlimab
A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/L2
Participant Group/Arm
EXPERIMENTAL: Expansion (Part 2) - Arm C
Participants will receive PF-07820435 orally at the prescribed dose and frequency in 28-day cycles
Intervention/Treatment
DRUG: PF-07820435
immune agonist
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 (Arm A) must have received platinum-based chemotherapy and anti-PD-(L)1 or have intolerability to or refusal of standard therapies. NSCLC participants with known activating mutation(s) must also have received prior approved and available targeted therapy(ies) for the associated mutation(s) or have intolerability or documented refusal of these therapies. Participants with UC (Arm B) must have received prior platinum-based chemotherapy, anti-PD-(L)1 therapy, or enfortumab vedotin, or have documented intolerability or refusal of the standard therapy(ies). Additional cohort indication(s) or dose regimens may be added and defined based on emerging data
- 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
- Active or history of clinically significant gastrointestinal disease and other conditions that are unresolved or pose a risk to study treatment or procedures
- Active or history of pneumonitis/interstitial lung disease, pulmonary fibrosis requiring treatment with systemic steroid therapy
- Active or history of clinically significant autoimmune disease or other medical condition that required chronic systemic immunosuppressive therapy within recent 2 years
- 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
- February 2024
Estimated primary completion date
- January 2028
Key endpoints
Primary Outcome Measures
Outcome Measure
Number of patients with dose limiting toxicities (DLTs) in dose escalation (Part 1A and Part 1B)
Measure Description
DLT rate estimated based on data from DLT-evaluable participants during the DLT evaluation period
Time Frame
Baseline through 28 days after first dose
Outcome Measure
Number of patients with adverse events (AEs)
Measure Description
Characterized by type, frequency, severity (CTCAE v5; CRS by ASTCT), timing, seriousness, and relationship to study drug(s)
Time Frame
Baseline through up to 2 years
Outcome Measure
Number of patients with clinically significant lab abnormalities
Measure Description
Characterized by type, frequency, severity (CTCAE v5), and timing
Time Frame
Baseline through up to 2 years
Outcome Measure
Objective response rate (ORR) in Part 2 Expansion
Measure Description
Tumor response as assessed using RECIST 1.1
Time Frame
Baseline through 2 years or disease progression
Secondary Outcome Measures:
Outcome Measure
Objective response rate (ORR) in dose escalation (Part 1A and Part 1B)
Measure Description
Tumor response as assessed by RECIST 1.1
Time Frame
Baseline through 2 years or disease progression
Outcome Measure
Duration of tumor response
Measure Description
Tumor response as assessed by RECIST 1.1
Time Frame
Baseline through 2 years or disease progression
Outcome Measure
Progression free survival (PFS)
Measure Description
Tumor response as assessed by RECIST 1.1
Time Frame
Baseline through 2 years or disease progression
Outcome Measure
Cmax (maximum concentration) of PF-07820435 and its active metabolite
Measure Description
Single and multiple dose PK parameters of PF-07820435 and its active metabolite
Time Frame
Serial timepoints following the first dose (Day 1), second dose (Day 8), and third dose (Day 15) of the first cycle (each cycle is 28 days); and Day 1 (dosing) of Cycle 2 and Day 1 (dosing) of Cycle 3.
Outcome Measure
Tmax (time to maximal plasma concentration) of PF-07820435 and its active metabolite
Measure Description
Single and multiple dose PK parameters of PF-07820435 and its active metabolite
Time Frame
Serial timepoints following the first dose (Day 1), second dose (Day 8), and third dose (Day 15) of the first cycle (each cycle is 28 days); and Day 1 (dosing) of Cycle 2 and Day 1 (dosing) of Cycle 3.
Outcome Measure
AUClast (area under the curve from time 0 to the last measurable timepoint) of PF-07820435 and its active metabolite
Measure Description
Single and multiple dose PK parameters of PF-07820435 and its active metabolite
Time Frame
Serial timepoints following the first dose (Day 1), second dose (Day 8), and third dose (Day 15) of the first cycle (each cycle is 28 days); and Day 1 (dosing) of Cycle 2 and Day 1 (dosing) of Cycle 3.
Outcome Measure
Cmin (minimum concentration) of PF-07820435 and its active metabolite after multiple dosing only
Measure Description
Multiple dose PK parameters of PF-07820435 and its active metabolite
Time Frame
Serial timepoints following the first dose (Day 1), second dose (Day 8), and third dose (Day 15) of the first cycle (each cycle is 28 days); and Day 1 (dosing) of Cycle 2 and Day 1 (dosing) of Cycle 3.
Outcome Measure
Change from baseline of immune markers within biopsied tumor tissue
Measure Description
Change in CD8 immune marker will be analyzed
Time Frame
Baseline through about 6 weeks after first dose
Outcome Measure
Pre-dose trough concentrations of sasanlimab (Part 1B and Part 2)
Measure Description
Single and multiple dose PK parameters of sasanlimab
Time Frame
Day 1 (pre-dose) of each cycle (28 days) for the first 3 cycles, then Day 1 on every 3rd cycle until 2 years or disease progression
Outcome Measure
Incidence and titers of ADA and NAb against sasanlimab (Part 1B and Part 2)
Measure Description
Immunogenicity assessment
Time Frame
Day 1 (pre-dose) of each cycle (28 days) for the first 3 cycles, then Day 1 on every 3rd cycle until 2 years or disease progression
Outcome Measure
Cmax of PF-07820435 and its active metabolite under fasted and fed conditions (Part 2 subset) subset of participants in Part 2
Measure Description
The analysis applies to Part 2 Food Effect Subset only
Time Frame
On Day 1 (first dose) and Day 15 (third dose): Pre-dose, 0.5 hour (h), 1h, 2h, 4h, 6h, and 24h post dose.
Outcome Measure
Tmax of PF-07820435 and its active metabolite under fasted and fed conditions (Part 2 subset) subset of participants in Part 2
Measure Description
The analysis applies to Part 2 Food Effect Subset only
Time Frame
On Day 1 (first dose) and Day 15 (third dose): Pre-dose, 0.5 hour (h), 1h, 2h, 4h, 6h, and 24h post dose.
Outcome Measure
AUC of PF-07820435 and its active metabolite under fasted and fed conditions (Part 2 subset) subset of participants in Part 2
Measure Description
The analysis applies to Part 2 Food Effect Subset only
Time Frame
On Day 1 (first dose) and Day 15 (third dose): Pre-dose, 0.5 hour (h), 1h, 2h, 4h, 6h, and 24h post dose.
Number of participants
140
Collaborators and investigators
Sponsor: Pfizer
Collaborator: None