A Study of PF-07260437 in Advanced or Metastatic Solid Tumors

Laboratory parameters included: hematology (hemoglobin, hematocrit, red blood cell, platelet and white blood cell count, neutrophils, eosinophils, monocytes, basophils and lymphocytes), chemistry (blood urea nitrogen, creatinine, sodium, potassium, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein and serum pregnancy test \[for all female participants\]) and urine (urine pregnancy test \[for all female participants\]). Clinical significance of laboratory parameters was determined at the investigator's discretion.

Time frame: Baseline through up to 35.1 weeks

Population: All enrolled participants who received at least one dose of study intervention were included in the analysis.

Any of the following treatment-related adverse events (AEs) occurring during the DLT observation period were classified as DLTs: Hematological DLTs: neutropenia Grade (G) 4, febrile neutropenia, ≥G3 for \>7d (days), G3 with infection; thrombocytopenia G4, G3 with bleeding or requiring platelet transfusion; anemia G4, G3 requiring blood transfusion. Non-hematologic: hepatic toxicity; ≥G3 fatigue for ≥5d, ≥G3 nausea/vomiting or diarrhea for ≥3d, ≥G3 cytokine release syndrome (CRS) of any duration/QTcF prolongation/anaphylaxis, G5 AE without clear reason; immune-related (ir)AE: ≥G4 irAEs/colitis, G3/4 non-infectious pneumonitis, G2 pneumonitis not resolved to ≤G1 within 3d of the initiation of max supportive care. Severity of AEs were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, with the exception of CRS, which were graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading for CRS.

Time frame: The first dose of the study intervention (C1D1) through Day 28 for participants without a priming dose or through Day 42 for participants with a priming dose.

Population: DLT evaluable set included all enrolled participants who had at least 1 dose of study intervention and either experienced DLT or did not have major protocol deviations during the DLT observation period.

An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAE was defined as any AE that occurred from first dose of study intervention to either last dose of study treatment + 90 days, start of new anti-cancer therapy, or completion in study as determined by disposition, whichever was earliest. A serious AE (SAE) was defined as any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, persistent disability/incapacity, or was a congenital anomaly/birth defect. AEs were graded by the investigator according to CTCAE v5.0.

Time frame: Baseline (Day 1 of dosing ) through 4 week follow-up, up to 35.1 weeks

Population: All enrolled participants who received at least one dose of study intervention were included in the analysis.

Number of participants with positive ADA against PF-07257876 were summarized for each treatment arm. A participant had treatment-induced ADA response if he/she had negative or missing ADA at baseline and ≥1 post-treatment ADA positive titer. A participant had treatment-boosted ADA response if he/she had positive titer at baseline and a ratio of ≥4 in titer (dilution) to baseline in ≥1 post-treatment sample.

Time frame: On Day 1 of Cycle 1, 2, 3. From Cycle 4 onwards: collection on Day 1 of every 3 cycles (C4D1, C7D1, etc.) until end-of-treatment visit, up to 35.1 weeks.

Population: The immunogenicity analysis set included all enrolled participants who received at least 1 dose of study treatment and had at least 1 sample tested for ADA.

irAEs included gastrointestinal (ie, diarrhea/colitis), dermatological (ie, rash), pulmonary (ie, pneumonitis), hepatic (ie, liver test elevation), renal (ie, creatinine increased), cardiac (ie, myocarditis), endocrine (ie, endocrine disorder), and other toxicities.

Time frame: Day 1 up to 90 days after the last dose of study intervention (Day 246 [C9D15]), up to approximately 336 days

Population: All enrolled participants who receive at least 1 dose of study intervention were included in the analysis.

Area under the plasma concentration-time profile from time 0 to time tau (τ), the dosing interval following single dose of PF-07260437. The multiple dose PK samples were not collected due to dose interruption or discontinuation. The PK sampling schedule was designed to evaluate the dosing interval of 2 weeks. Since the 100/300/800 group received the second dose (300 ug) only 1 week after the first dose. The PK parameters were not calculable.

Time frame: Day 1 pre-dose, 1, 4, 8, 24, 48 and 168 hours post-dose, till Day 15 pre-dose in Cycle 1

Population: All enrolled participants treated who did not have protocol deviations influencing PK assessment and had sufficient information to estimate at least 1 of the PK parameters of interest. Participants with ≤3 sampling points or missing PK samples on day 14 were excluded. Participants in 200/500, 200/800, 200/1600 groups received the same dose on Day 1, and therefore, were combined for single dose (200 ug) PK to increase the sample size and provide more confidence to the estimate.

Maximum observed serum concentration following single dose of PF-07260437. The multiple dose PK samples were not collected due to dose interruption or discontinuation. The PK sampling schedule was designed to evaluate the dosing interval of 2 weeks. Since the 100/300/800 group received the second dose (300 ug) only 1 week after the first dose. The PK parameters were not calculable.

Time frame: Day 1 pre-dose, 1, 4, 8, 24, 48 and 168 hours post-dose, till Day 15 pre-dose in Cycle 1

Population: All enrolled participants treated who did not have protocol deviations influencing PK assessment and had sufficient information to estimate at least 1 of the PK parameters of interest. Participants with ≤3 sampling points or missing PK samples on day 14 were excluded. Participants in 200/500, 200/800, 200/1600 groups received the same dose on Day 1, and therefore, were combined for single dose (200 ug) PK to increase the sample size and provide more confidence to the estimate.

Time to maximal plasma concentration following single dose of PF-07260437. The multiple dose PK samples were not collected due to dose interruption or discontinuation. The PK sampling schedule was designed to evaluate the dosing interval of 2 weeks. Since the 100/300/800 group received the second dose (300 ug) only 1 week after the first dose. The PK parameters were not calculable.

Time frame: Day 1 pre-dose, 1, 4, 8, 24, 48 and 168 hours post-dose, till Day 15 pre-dose in Cycle 1

Population: All enrolled participants treated who did not have protocol deviations influencing PK assessment and had sufficient information to estimate at least 1 of the PK parameters of interest. Participants with ≤3 sampling points or missing PK samples on day 14 were excluded. Participants in 200/500, 200/800, 200/1600 groups received the same dose on Day 1, and therefore, were combined for single dose (200 ug) PK to increase the sample size and provide more confidence to the estimate.