A Study of PF-07820435 as a Single Agent and in Combination in Participants With Advanced Solid Tumors

JRCT ID: jRCT2031230747

Registered date:28/03/2024

Basic Information

• Recruitment status: Recruiting

Health condition(s) or Problem(s) studied

* Neoplasms
* Non-small-cell Lung Cancer
* Urothelial Carcinoma
* (and 5 more...)

• Date of first enrollment: 09/04/2024
• Target sample size: 140
• Countries of recruitment: United States,Japan
• Study type: Interventional

Intervention(s)

Drug: PF-07820435
immune agonist

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

Outcome(s)

Primary Outcome

Primary Outcome Measures :
1.Number of patients with dose limiting toxicities (DLTs) in dose escalation (Part 1A and Part 1B) [ Time Frame: Baseline through 28 days after first dose ]
DLT rate estimated based on data from DLT-evaluable participants during the DLT evaluation period

2.Number of patients with adverse events (AEs) [ Time Frame: Baseline through up to 2 years ]
Characterized by type, frequency, severity (CTCAE v5; CRS by ASTCT), timing, seriousness, and relationship to study drug(s)

3.Number of patients with clinically significant lab abnormalities [ Time Frame: Baseline through up to 2 years ]
Characterized by type, frequency, severity (CTCAE v5), and timing

4.Objective response rate (ORR) in Part 2 Expansion [ Time Frame: Baseline through 2 years or disease progression ]
Tumor response as assessed using RECIST 1.1

Secondary Outcome

Secondary Outcome Measures:
1.Objective response rate (ORR) in dose escalation (Part 1A and Part 1B) [ Time Frame: Baseline through 2 years or disease progression ]
Tumor response as assessed by RECIST 1.1

2.Duration of tumor response [ Time Frame: Baseline through 2 years or disease progression ]
Tumor response as assessed by RECIST 1.1

3.Progression free survival (PFS) [ Time Frame: Baseline through 2 years or disease progression ]
Tumor response as assessed by RECIST 1.1

4.Cmax (maximum concentration) 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. ]
Single and multiple dose PK parameters of PF-07820435 and its active metabolite

5.Tmax (time to maximal plasma concentration) 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. ]
Single and multiple dose PK parameters of PF-07820435 and its active metabolite

6.AUClast (area under the curve from time 0 to the last measurable timepoint) 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. ]
Single and multiple dose PK parameters of PF-07820435 and its active metabolite

7.Cmin (minimum concentration) of PF-07820435 and its active metabolite after multiple dosing only [ 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. ]
Multiple dose PK parameters of PF-07820435 and its active metabolite

8.Change from baseline of immune markers within biopsied tumor tissue [ Time Frame: Baseline through about 6 weeks after first dose ]
Change in CD8 immune marker will be analyzed

9.Pre-dose trough concentrations of sasanlimab (Part 1B and Part 2) [ 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 ]
Single and multiple dose PK parameters of sasanlimab

10.Incidence and titers of ADA and NAb against sasanlimab (Part 1B and Part 2) [ 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 ]
Immunogenicity assessment

11.Cmax of PF-07820435 and its active metabolite under fasted and fed conditions (Part 2 subset) subset of participants in Part 2 [ 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. ]
The analysis applies to Part 2 Food Effect Subset only

12.Tmax of PF-07820435 and its active metabolite under fasted and fed conditions (Part 2 subset) subset of participants in Part 2 [ 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. ]
The analysis applies to Part 2 Food Effect Subset only

13.AUC of PF-07820435 and its active metabolite under fasted and fed conditions (Part 2 subset) subset of participants in Part 2 [ 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. ]
The analysis applies to Part 2 Food Effect Subset only

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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

Exclude criteria

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

Related Information

• Primary Sponsor: Kawai Norisuke
• Secondary ID(s): NCT06285097