The purpose of this study is to learn about the safety (the impact of the study drug on the participant's body), effects of the study drug alone or in combination with bevacizumab or sasanlimab, and to find the best dose. This study is seeking participants who have solid tumors that: * have advanced (cancer that doesn't disappear or stay away with treatment) or * has spread to other parts of the body (metastatic). This includes (but limited to) the following cancer types: * Non-Small Cell Lung Cancer (NSCLC): It's a type of lung cancer where the cells grow slowly but often spread to other parts of the body. * Colorectal Cancer (CRC): This is a disease where cells in the colon or rectum grow out of control. * Urothelial Cancer (UC): This is a cancer that starts in the urinary systems. * Melanoma: Skin cancer that develops when melanocytes (the cells that give the skin its tan or brown color) start to grow out of control. All participants in this study will receive the study medication (PF-07329640) as an IV infusion (given directly into a vein) at the study clinic every week for repeating 28-day cycles. Depending on which part of the study participants are enrolled in they will receive the study medication (PF-07329640 alone or in combination with other anti-cancer medications (bevacizumab or sasanlimab). Bevacizumab is given in the clinic as IV infusion every two weeks and sasanlimab is given as a shot under the skin every 4 weeks. Participants can continue to take the study medication (PF-07329640) and bevacizumab until their cancer is no longer responding. Participants who are taking sasanlimab may receive it for up to 2 years. The study will look at the experiences of people receiving the study medicines. This will help see if the study medicines are safe and effective. Participants will be involved in this study for up to 4 years. During this time, they will have a study visit every week. After they have stopped taking the study medication (at about at 2 years) they will be followed for another two years to see how they are doing.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
4
an anti-lymphotoxin beta receptor agonist
A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/L2
a monoclonal antibody that blocks VEGF
Highlands Oncology
Fayetteville, Arkansas, United States
Highlands Oncology
Rogers, Arkansas, United States
Highlands Oncology Group
Springdale, Arkansas, United States
NEXT Oncology
San Antonio, Texas, United States
Hospital Oncológico Dr. Isaac González-Martinez
Rio Piedras, Puerto Rico
Pan American Center for Oncology Trials, LLC
Rio Piedras, Puerto Rico
Pan American Center for Oncology Trials- Hospital Oncologico
Rio Piedras, Puerto Rico
PART 1: Number of participants with Dose-limiting toxicities (DLT)
Any of the prespecified AEs that are attributable to one, the other, or both study treatments, occurring in the DLT observation period are considered DLTs, excluding toxicities clearly due to underlying disease or extraneous causes:
Time frame: First cycle, Day 1 up to Day 28
PART 1 & 2: Incidence of Adverse Events (AE)s
An adverse event (AE) was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/ incapacity; congenital anomaly. AEs included both serious and all non-serious AEs.
Time frame: From start of the treatment up to 90 days after last dose or start of new anticancer therapy, whichever occurred first
To: PART 1 & 2: Number of participants with laboratory abnormalities
Number of participants with laboratory test abnormalities. Laboratory test parameters included hematology, coagulation, liver function, renal function, electrolytes, clinical chemistry, and urinalysis (dipstick and microscopy).
Time frame: From start of treatment up to 90 days after last dose or start of new anticancer therapy, whichever occurred first
Part 2: "Objective Response - Number of Participants With Objective Response "
Percentage of participants with objective response-based best overall response (BOR) of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) assessed by the Investigator.
Time frame: Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion, approximately 2 years'
Part 1: Objective Response - Number of Participants With Objective Response
Percentage of participants with objective response-based assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) assessed by the Investigator
Time frame: Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion, approximately 2 years
Time to event endpoints: duration of response (DOR) by RECIST v1.1
Time to event: DOR according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as assessed by the Investigator.
Time frame: Baseline to confirmed disease progression, up to 2 years after the last dose of study treatmennt
Time to event endpoints: progression-free survival (PFS) by RECIST v1.1
Time to event: PFS according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as assessed by the Investigator.
Time frame: Baseline to confirmed disease progression, up to 2 years after the last dose of study treatmennt
Part 1A: Maximum Observed Serum Concentration (Cmax) of PF-07329640
Cycle 1: Pre-dose, End of Infusion (EOI), 4, and 8 hours Cycle 2: Pre-dose, EOI, 4, and 8 hours
Time frame: Cycle 1 Day 1 & Cycle 2 Day 1 (each cycle is 28 days)
Part 1A: Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-07329640
Cycle 1: Pre-dose, End of Infusion (EOI), 4, and 8 hours Cycle 2: Pre-dose, EOI, 4, and 8 hours
Time frame: Cycle 1 Day 1 & Cycle 2 Day 1 (each cycle is 28 days)
Part 1A: Serum Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-07329640
Cycle 1: Pre-dose, End of Infusion (EOI), 4, 8, 24, 48, 72 hours post-dose (Day 1-4); Pre-dose, EOI, 4 hours post-dose (Day 8); pre-dose, EOI (Day 15) Cycle 2: Pre-dose, EOI, 4, 8, 24, 48, 72 hours post-dose (Day 1-4); Pre-dose, and 4 hours post-dose (Day 15)
Time frame: Cycle 1 Day 1 & Cycle 2 Day 1 (each cycle is 28 days)
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Serum Concentrations of PF-07329640 in combination (Part 1B/1C/2A/2B/2C)
comparison Predose and end of infusion blood serum concentrations at Cycle 1 day 1 and 15, and Cycle Day 1
Time frame: pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1Day 15, Cycle 2 Day 1 (Each cycle is 28 days)
Incidence and titers of antidrug antibodies (ADA) against PF-07329640
the number of patients with ADAs against PF-07329640 and the concentration of those ADAs
Time frame: Baseline though study completion, an average of 2 years
Paired Tumor Biopsies
Changes in quantity and maturation state of tertiary lymphoid structure (TLS)s in tumor biopsy tissues at Cycle 2 Day 15
Time frame: Baseline through Cycle 2 Day 15 (each cycle is 28 days)