Advanced Solid Tumors, Gastric Cancer, Gastroesophageal Junction Cancer, Urothelial Cancer, Non Small Cell Lung Cancer, Head and Neck Squamous Cell Carcinomas
Conditions
Keywords
immunotherapy, advanced solid tumor, metastatic solid tumor, first in human, Gastric cancer, Gastroesophageal junction cancer, Urothelial Cancer, Non small cell lung cancer, Head and neck squamous cell carcinomas, SCCHN, NSCLC, Lung cancer, Hematopoietic progenitor kinase 1 inhibitor, HPK1 inhibitor
Brief summary
The purpose of this study is to assess the safety and effects of PF-07265028 as monotherapy and in combination with sasanlimab. The study aims to identify the maximum tolerated dose (MTD) of PF-07265028 as monotherapy; evaluate the clinical activity of monotherapy and combination; and select the recommended dose of PF-07265028 monotherapy and in combination for potential further studies and development. The study contains 2 parts, Dose Escalation (Part 1) to determine the recommended dose of PF-07265028 as single agent and in combination, followed by Dose Expansion (Part 2) in selected tumor types at the recommended dose. It is expected that most participants will take part in this study for up to 1 year with six on-site visits in the first month and then at least twice every subsequent month while they are on treatment.
Detailed description
The purpose of this first-in-human study is to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of increasing doses of PF-07265028 as monotherapy and in combination with sasanlimab; identify the maximum tolerated dose (MTD) of PF-07265028 monotherapy; evaluate the clinical activity of monotherapy and combination; and select the recommended dose of PF-07265028 monotherapy and in combination for potential further studies and development. The study contains 2 parts, Dose Escalation (Part 1) to determine the recommended dose of PF-07265028 as single agent and in combination, followed by Dose Expansion (Part 2) in selected tumor types at the recommended dose.
Interventions
DRUGPF-07265028
PF-07265028 will be administered orally
BIOLOGICALSasanlimab
Administered subcutaneously
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: Across all cohorts: 1. Eastern Cooperative Oncology Group (ECOG) performance status ≤1 2. Adequate hematological, kidney and liver function 3. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. 4. Resolved acute effects of any prior therapy 5. All participants must provide archival formalin-fixed paraffin-embedded (FFPE) tumor tissue: Part 1: If archival sample is older than 6 months, the participant must consent to undergo a fresh biopsy during the screening. Part 2 Fresh tumor biopsy during screening is required unless there is archival tissues less than 3 months old and subsequent to the last systemic anti-cancer therapy. Part 1A Monotherapy: Histologically or cytologically confirmed advanced or metastatic solid tumors which have progressed following systemic anticancer therapies, or are resistant to standard therapy or for which no standard therapy is available, or for whom standard therapy is not tolerated. Part 1B Combination Therapy: Histologically or cytologically confirmed advanced or metastatic solid tumor which have progressed following systemic anticancer therapies, including at least 1 checkpoint inhibitor. Part 2 Dose Expansion: Histologically or cytologically confirmed advanced or metastatic malignancies, including gastric/Gastroesophageal junction cancer, Head and neck squamous cell carcinoma, or urothelial cancer (non-small cell lung cancer and other solid tumors may be included) who have progressed following systemic anticancer therapies, including at least 1 checkpoint inhibitor Key
Exclusion criteria
1. Participants with any other active malignancy within 3 years prior to enrollment 2. Participants with active autoimmune conditions or history of autoimmune diseases that may relapse 3. History of interstitial lung disease, pneumonitis (non-infectious) or uncontrolled lung diseases 4. History of prior immune-related adverse events (irAEs) Grade ≥3 5. Central nervous system metastases 6. Significant cardiac or pulmonary conditions or events within previous 6 months 7. Active, uncontrolled bacterial, fungal, or viral infection 8. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PF-07265028 9. Prior administration of HPK1 inhibitor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Dose-limiting toxicities (DLTs) in Dose Escalation (Part 1) | Cycle 1 (28 days) | DLTs will be evaluated during Cycle 1 (a cycle is 28 days) in Part 1. The number of DLTs will be used to determine the optimal dose |
| Number of participants with adverse events (AEs) | Baseline through up to 2 years | AEs characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] version 5.0), timing, seriousness, and relationship to study therapy. |
| Number of participants with clinically significant laboratory abnormalities | Baseline through up to 2 years | Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing. |
| Objective response rate (ORR) in Dose Expansion (Part 2) | Baseline through up to 2 years or until disease progression | Tumor response based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The pharmacokinetic profile of single and multiple doses PF-07265028 alone and in combination with sasanlimab through Cmax. | Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days) | Maximum observed plasma concentration of PF-07265028 (Cmax) and Maximum observed steady state plasma concentration (Cmax, ss) |
| The pharmacokinetic profile of single and multiple doses PF-07265028 alone and in combination with sasanlimab through Tmax. | Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days) | Time to maximal observed plasma concentration of PF-07265028 (Tmax) and Time to reach Maximum Observed Steady State Plasma Concentration (Tmax,ss). |
| The pharmacokinetic profile of single and multiple doses PF-07265028 alone and in combination with sasanlimab through AUC | Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days) | Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast) of PF-07265028 and area under the curve within one dose interval at steady state (AUCtau,ss) |
| The effect of food on the pharmacokinetic profile of PF-07265028 through Cmax. | Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days) | Maximum observed plasma concentration of PF-07265028 (Cmax) under fasted and fed conditions in the subset of participants |
| The effect of food on the pharmacokinetic profile of PF-07265028 through Tmax | Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days) | Time to maximal observed plasma concentration of PF-07265028 (Tmax) under fasted and fed conditions in the subset of participants |
| The effect of food on the pharmacokinetic profile of PF-07265028 through AUC | Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days) | Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast) of PF-07265028 under fasted and fed conditions in the subset of participants |
| The pharmacokinetic profile of sasanlimab when given in combination with PF-07265028 through Cmin | Day 1 of cycle 1 (each cycle is 28 days), Day 1 of cycle 2, Day 1 of cycle 3, Day 1 of cycle 5 and thereafter every 6 cycles (each cycle is 28 days) | Minimum plasma concentration (Cmin) will be calculated through the measured pre-dose plasma concentration |
| The immunogenicity of sasanlimab when given in combination with PF-07265028 through ADA and NAb | Day 1 of cycle 1 (each cycle is 28 days), Day 1 of cycle 2, Day 1 of cycle 3, Day 1 of cycle 5 and thereafter every 6 cycles (each cycle is 28 days) | Incidence and titers of anti-drug antibodies (ADA) and neutralizing antibodies (NAb) against sasanlimab |
| The effect of PF-07265028 alone and in combination with sasanlimab on tumor immune biomarkers modulation | Baseline through up to 2 years | Levels of intratumor T cells and PD-L1 expression in pre- and post-treatment tumor biopsies |
| ORR in Dose Escalation (Part 1) | From baseline through disease progression or study completion (approximately 2 years) | Tumor response assessment based on RECIST 1.1 |
| Time to event endpoints (DOR) in Dose Expansion (Part 2) | From baseline through disease progression or study completion (approximately 2 years) | Duration of response (DOR) as assessed using RECIST 1.1. |
| Time to event endpoints (PFS) in Dose Expansion (Part 2) | From baseline through disease progression or study completion (approximately 2 years) | Progression free survival (PFS) as assessed using RECIST 1.1. |
| Time to event endpoints (OS) in Dose Expansion (Part 2) | From baseline through disease progression or study completion (approximately 2 years) | Overall survival (OS) assessed proportion of patients alive |
Countries
Japan, United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed