Neoplasms, Non-small-cell Lung Cancer, Melanoma, Squamous Cell Carcinoma of the Head and Neck, Renal Cell Carcinoma, Urothelial Carcinoma, Colorectal Carcinoma, Ovarian Carcinoma
Conditions
Keywords
Sasanlimab, anti-Programmed death receptor-1 (PD-1), solid tumor, immunotherapy
Brief summary
This study aims to evaluate the safety, and early signals of anti-tumor activity of PF-07820435 when administered alone (Part 1A) or in combination with sasanlimab (Part 1B; Part 2) in patients with selected advanced or metastatic solid tumors. Part 1 will be dose-finding and Part 2 of the study will further evaluate PF-07820435 at the recommended dose for combination expansion in patients with selected advanced solid tumors.
Interventions
DRUGPF-07820435
immune agonist
BIOLOGICALSasanlimab
A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/L2
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 (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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with dose limiting toxicities (DLTs) in dose escalation (Part 1A and Part 1B) | Baseline through 28 days after first dose | DLT rate estimated based on data from DLT-evaluable participants during the DLT evaluation period |
| Number of patients with adverse events (AEs) | Baseline through up to 2 years | Characterized by type, frequency, severity (CTCAE v5; CRS by ASTCT), timing, seriousness, and relationship to study drug(s) |
| Number of patients with clinically significant lab abnormalities | Baseline through up to 2 years | Characterized by type, frequency, severity (CTCAE v5), and timing |
| Objective response rate (ORR) in Part 2 Expansion | Baseline through 2 years or disease progression | Tumor response as assessed using RECIST 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax (time to maximal plasma concentration) of PF-07820435 and its active metabolite | 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 |
| AUClast (area under the curve from time 0 to the last measurable timepoint) of PF-07820435 and its active metabolite | 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 |
| Cmin (minimum concentration) of PF-07820435 and its active metabolite after multiple dosing only | 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 |
| Change from baseline of immune markers within biopsied tumor tissue | Baseline through about 6 weeks after first dose | Change in CD8 immune marker will be analyzed |
| Objective response rate (ORR) in dose escalation (Part 1A and Part 1B) | Baseline through 2 years or disease progression | Tumor response as assessed by RECIST 1.1 |
| Incidence and titers of ADA and NAb against sasanlimab (Part 1B and Part 2) | 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 |
| Cmax of PF-07820435 and its active metabolite under fasted and fed conditions (Part 2 subset) subset of participants in Part 2 | 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 |
| Tmax of PF-07820435 and its active metabolite under fasted and fed conditions (Part 2 subset) subset of participants in Part 2 | 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 |
| AUC of PF-07820435 and its active metabolite under fasted and fed conditions (Part 2 subset) subset of participants in Part 2 | 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 |
| Pre-dose trough concentrations of sasanlimab (Part 1B and Part 2) | 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 |
| Duration of tumor response | Baseline through 2 years or disease progression | Tumor response as assessed by RECIST 1.1 |
| Progression free survival (PFS) | Baseline through 2 years or disease progression | Tumor response as assessed by RECIST 1.1 |
| Cmax (maximum concentration) of PF-07820435 and its active metabolite | 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 |
Countries
Japan, Puerto Rico, United States
Outcome results
None listed