Clinical trial NCT06285097: A Study of PF-07820435 as a Single Agent and in Combination in Participants With Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Neoplasms
Non-small-cell Lung Cancer
Melanoma
Squamous Cell Carcinoma of the Head and Neck
Renal Cell Carcinoma
Urothelial Carcinoma
Colorectal Carcinoma
Ovarian Carcinoma
Keywords: Sasanlimab
anti-Programmed death receptor-1 (PD-1)
solid tumor
immunotherapy
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2024-02-29
Enrollment: 9
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: 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.


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

Primary outcomes:
measure: Number of patients with dose limiting toxicities (DLTs) in dose escalation (Part 1A and Part 1B)
timeFrame: Baseline through 28 days after first dose
measure: Number of patients with adverse events (AEs)
timeFrame: Baseline through up to 2 years
measure: Number of patients with clinically significant lab abnormalities
timeFrame: Baseline through up to 2 years
measure: Objective response rate (ORR) in Part 2 Expansion
timeFrame: Baseline through 2 years or disease progression
Secondary outcomes:
measure: Objective response rate (ORR) in dose escalation (Part 1A and Part 1B)
timeFrame: Baseline through 2 years or disease progression
measure: Duration of tumor response
timeFrame: Baseline through 2 years or disease progression
measure: Progression free survival (PFS)
timeFrame: Baseline through 2 years or disease progression
measure: Cmax (maximum concentration) of PF-07820435 and its active metabolite
timeFrame: 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.
measure: Tmax (time to maximal plasma concentration) of PF-07820435 and its active metabolite
timeFrame: 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.
measure: AUClast (area under the curve from time 0 to the last measurable timepoint) of PF-07820435 and its active metabolite
timeFrame: 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.
measure: Cmin (minimum concentration) of PF-07820435 and its active metabolite after multiple dosing only
timeFrame: 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.
measure: Change from baseline of immune markers within biopsied tumor tissue
timeFrame: Baseline through about 6 weeks after first dose
measure: Pre-dose trough concentrations of sasanlimab (Part 1B and Part 2)
timeFrame: 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
measure: Incidence and titers of ADA and NAb against sasanlimab (Part 1B and Part 2)
timeFrame: 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
measure: Cmax of PF-07820435 and its active metabolite under fasted and fed conditions (Part 2 subset) subset of participants in Part 2
timeFrame: On Day 1 (first dose) and Day 15 (third dose): Pre-dose, 0.5 hour (h), 1h, 2h, 4h, 6h, and 24h post dose.
measure: Tmax of PF-07820435 and its active metabolite under fasted and fed conditions (Part 2 subset) subset of participants in Part 2
timeFrame: On Day 1 (first dose) and Day 15 (third dose): Pre-dose, 0.5 hour (h), 1h, 2h, 4h, 6h, and 24h post dose.
measure: AUC of PF-07820435 and its active metabolite under fasted and fed conditions (Part 2 subset) subset of participants in Part 2
timeFrame: On Day 1 (first dose) and Day 15 (third dose): Pre-dose, 0.5 hour (h), 1h, 2h, 4h, 6h, and 24h post dose.
Other outcomes:
Locations:
city: Sarasota
country: United States
facility: Florida Cancer Specialists Sarasota Drug Development Unit
state: Florida
city: Grand Rapids
country: United States
facility: Corewell Health (reference non-engagement letter)
state: Michigan
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Nashville
country: United States
facility: Sarah Cannon Research Institute - Pharmacy
state: Tennessee
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Nashville
country: United States
facility: Tristar Centennial Medical Center
state: Tennessee
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Koto
country: Japan
facility: The Cancer Institute Hospital of JFCR
state: Tokyo
city: Rio Piedras
country: Puerto Rico
facility: Hospital Oncologico Dr. Isaac Gonzalez-Martinez
city: Rio Piedras
country: Puerto Rico
facility: Pan American Center for Oncology Trials, LLC
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: