Carcinoma, Non Small Cell Lung, Carcinoma, Pancreatic Ductal, Malignant Melanoma, Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Conditions
Keywords
Advanced solid tumors, NSCLC, PDAC, HNSCC, ISAC, ADC, PD-L1 inhibitor
Brief summary
The purpose of this study is to learn about the safety and the effects of PF-08046037 alone or with sasanlimab for the treatment of certain advanced or metastatic malignancies. This study is seeking participants who: * have advanced or metastatic non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), melanoma, or pancreatic ductal adenocarcinoma (PDAC); * are able to provide tumor tissue samples; * have measurable disease. All participants will receive while at the clinic PF-08046037 alone as an intravenous (IV) infusion (given directly into a vein) or with sasanlimab as a subcutaneous (SQ) injection (given under the skin) once every 3 weeks. Participants will continue to take the study drug(s) until their cancer is no longer responding or if the patient cannot safely take them. The study team will monitor how each participant is doing with the study treatment during regular visits at the study clinic.
Interventions
DRUGPF-08046037
Given into the vein (IV; intravenous)
DRUGsasanlimab
Given under the skin (SQ; subcutaneous)
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose escalation and expansion
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
This study is seeking participants who have the following tumor types and can provide tumor tissue samples as per below. 1. Tumor types * Monotherapy Dose Escalation (Part 1a) and Optimization (Part 2a) cohorts * Advanced or metastatic NSCLC, HNSCC, melanoma, or PDAC * Must have progressive disease following at least 1 prior approved systemic therapy * Monotherapy Dose Expansion (Part 3a) • Advanced or metastatic NSCLC or PDAC * Combination Safety Evaluation (Part 1b) and Dose Optimization (Part 2b) * Advanced or metastatic NSCLC or HNSCC * May be either a) not received prior immunotherapy for the tumor type OR b) relapse/ refractory after prior immunotherapy * Combination Dose Expansion (Part 3b) * Unresectable locally advanced or metastatic HNSCC or NSCLC * Must not have received prior systemic cytotoxic therapy in the locally advanced or metastatic setting (first-line setting) * Must be treatment naïve to any immunotherapy * NSCLC must have PD-L1 expression TPS \>=50% * HNSCC must have PD-L1 expression CPS \>=1 2. Tissue requirement * Part 1 at lower doses: sufficient archival tissue collected within 12 months of enrollment for submission to central laboratory * Part 1 at higher doses: de novo baseline tumor biopsy or archival tissue within 12 months of enrollment * Part 1 backfill: de novo baseline and on-treatment tumor biopsies are required * Part 2 and 3: de novo baseline or archival tissue within 6 months of enrollment * Part 2 and 3: mandatory on-treatment tumor biopsy, if required by sponsor 3. Measurable disease per RECIST v1.1 Participants who meet the following might not be able to participate. 1. History of Grade \>=3 immune mediated AE related to prior immune modulatory therapy and required immunosuppressive therapy 2. Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent 3. History of uveitis within the preceding 6 months 4. Clinically significant Grade \>=3 neurodegenerative disease 5. Grade 3 or higher pulmonary disease unrelated to underlying malignancy 6. Previous exposure to an investigational immunostimulatory antibody conjugate or systemic TLR agonist
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with DLTs by dose level | Up to 21 days | — |
| Number of participants with adverse events (AEs) | Through 30-37 days after the last study treatment, up to approximately 2 years | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention |
| Number of participants with laboratory abnormalities | Through 30-37 days after the last study treatment, up to approximately 2 years | — |
| Number of participants with dose-limiting toxicities (DLTs) | Up to 21 days | — |
| Number of dose modifications due to AEs | Through end of treatment up to approximately 2 years | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK parameter - Trough concentration (Ctrough) | Through 30-37 days after the last study treatment, up to approximately 2 years | PK endpoint |
| Number of participants with antidrug antibodies (ADAs) | Through 30-37 days after the last study treatment, up to approximately 2 years | — |
| Objective response rate (ORR) | Through end of study and up to approximately 2 years | The objective response rate (ORR) is defined as the percentage of participants with complete response (CR) or partial response (PR) which is subsequently confirmed as assessed according to Response Evaluation in Solid Tumors (RECIST) v1.1. |
| Best overall response | Through end of study and up to approximately 2 years | The best overall response for a participant will be determined by the order of confirmed CR, confirmed PR, stable disease (SD), progressive disease (PD), not evaluable (NE) or not applicable (NA) per RECIST v1.1. |
| Duration of response (DOR) | Through end of study and up to approximately 2 years | DOR is defined as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression per RECIST v1.1 or to death due to any cause |
| Progression-free survival (PFS) | Through end of study and up to approximately 2 years | PFS is defined as the time from start of PF-08046037 to first documentation of disease progression (based on radiographic assessments per RECIST v1.1) or death due to any cause, whichever comes first |
| Overall survival (OS) | Through end of study and up to approximately 2 years | OS is defined as the time from start of PF-08046037 to date of death due to any cause |
| Percent change of cells within tumors based on multiplex immunofluorescence | Through end of study and up to approximately 2 years | This measure will assess the number of immune cells, PD-1, PD-L1, and TLR7 expression within the tumor microenvironment. |
| Pharmacokinetic (PK) parameter - Area under the concentration-time curve (AUC) | Through 30-37 days after the last study treatment, up to approximately 2 years | PK endpoint |
| PK parameter - Maximum concentration (Cmax) | Through 30-37 days after the last study treatment, up to approximately 2 years | PK endpoint |
| PK parameter - Time to maximum concentration (Tmax) | Through 30-37 days after the last study treatment, up to approximately 2 years | PK endpoint |
| PK parameter - t1/2 | Through 30-37 days after the last study treatment, up to approximately 2 years | PK endpoint |
Countries
Puerto Rico, United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed