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

Melanoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06285097
• Other study ID #: C5391001
• Status: Recruiting
• Phase: Phase 1
• Start date: February 8, 2024
• Est. completion date: April 29, 2028

Study information

• Verified date: May 2024
• Source: Pfizer
• Contact: Pfizer CT.gov Call Center
• Phone: 1-800-718-1021
• Email: ClinicalTrials.gov_Inquiries[@]pfizer.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: April 29, 2028
• Est. primary completion date: April 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Colorectal Carcinoma
• Colorectal Neoplasms
• Melanoma
• Neoplasms
• Non-small-cell Lung Cancer
• Ovarian Carcinoma
• Renal Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck
• Squamous Cell Carcinoma of the Head and Neck
• Urothelial Carcinoma

Intervention

Drug:
• PF-07820435
immune agonist

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

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	The Cancer Institute Hospital of JFCR	Koto	Tokyo
Puerto Rico	Hospital Oncologico Dr. Isaac Gonzalez-Martinez	Rio Piedras
Puerto Rico	Pan American Center for Oncology Trials, LLC	Rio Piedras
United States	Corewell Health (reference non-engagement letter)	Grand Rapids	Michigan
United States	START Midwest	Grand Rapids	Michigan
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	Sarah Cannon Research Institute - Pharmacy	Nashville	Tennessee
United States	SCRI Oncology Partners	Nashville	Tennessee
United States	Tristar Centennial Medical Center	Nashville	Tennessee
United States	Florida Cancer Specialists Sarasota Drug Development Unit	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Japan,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with dose limiting toxicities (DLTs) in dose escalation (Part 1A and Part 1B)	DLT rate estimated based on data from DLT-evaluable participants during the DLT evaluation period	Baseline through 28 days after first dose
Primary	Number of patients with adverse events (AEs)	Characterized by type, frequency, severity (CTCAE v5; CRS by ASTCT), timing, seriousness, and relationship to study drug(s)	Baseline through up to 2 years
Primary	Number of patients with clinically significant lab abnormalities	Characterized by type, frequency, severity (CTCAE v5), and timing	Baseline through up to 2 years
Primary	Objective response rate (ORR) in Part 2 Expansion	Tumor response as assessed using RECIST 1.1	Baseline through 2 years or disease progression
Secondary	Objective response rate (ORR) in dose escalation (Part 1A and Part 1B)	Tumor response as assessed by RECIST 1.1	Baseline through 2 years or disease progression
Secondary	Duration of tumor response	Tumor response as assessed by RECIST 1.1	Baseline through 2 years or disease progression
Secondary	Progression free survival (PFS)	Tumor response as assessed by RECIST 1.1	Baseline through 2 years or disease progression
Secondary	Cmax (maximum concentration) of PF-07820435 and its active metabolite	Single and multiple dose PK parameters 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.
Secondary	Tmax (time to maximal plasma concentration) of PF-07820435 and its active metabolite	Single and multiple dose PK parameters 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.
Secondary	AUClast (area under the curve from time 0 to the last measurable timepoint) of PF-07820435 and its active metabolite	Single and multiple dose PK parameters 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.
Secondary	Cmin (minimum concentration) of PF-07820435 and its active metabolite after multiple dosing only	Multiple dose PK parameters 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.
Secondary	Change from baseline of immune markers within biopsied tumor tissue	Change in CD8 immune marker will be analyzed	Baseline through about 6 weeks after first dose
Secondary	Pre-dose trough concentrations of sasanlimab (Part 1B and Part 2)	Single and multiple dose PK parameters of sasanlimab	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
Secondary	Incidence and titers of ADA and NAb against sasanlimab (Part 1B and Part 2)	Immunogenicity assessment	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
Secondary	Cmax of PF-07820435 and its active metabolite under fasted and fed conditions (Part 2 subset) subset of participants in Part 2	The analysis applies to Part 2 Food Effect Subset only	On Day 1 (first dose) and Day 15 (third dose): Pre-dose, 0.5 hour (h), 1h, 2h, 4h, 6h, and 24h post dose.
Secondary	Tmax of PF-07820435 and its active metabolite under fasted and fed conditions (Part 2 subset) subset of participants in Part 2	The analysis applies to Part 2 Food Effect Subset only	On Day 1 (first dose) and Day 15 (third dose): Pre-dose, 0.5 hour (h), 1h, 2h, 4h, 6h, and 24h post dose.
Secondary	AUC of PF-07820435 and its active metabolite under fasted and fed conditions (Part 2 subset) subset of participants in Part 2	The analysis applies to Part 2 Food Effect Subset only	On Day 1 (first dose) and Day 15 (third dose): Pre-dose, 0.5 hour (h), 1h, 2h, 4h, 6h, and 24h post dose.

External Links

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